Sideeffekter fra Avandia kan ha skadet og drept 100 000 mennesker (aboutlawsuits.com 11.6.2010)
Glaxos legemiddelkatastrofe? (Glaxo's Drug Disaster?)
The biggest-selling diabetes drug in the world dramatically increases the risk of heart attacks and death from heart problems, according to an analysis by a top cardiologist published online in The New England Journal of Medicine. (forbes.com 21.5.2007)
Medisin kan gi infarkt (aftenposten.no 12.11.2007)
Glaxo publiserte ikke risiko for Avandia “Why would you publicize it?,'' Glaxo Chief Executive Officer Jean-Pierre Garnier told reporters (bloomberg.com 1.6.2007)
Om statlig legemiddelkontroll En annen side ved saken er at FDA er kommet i vanry som uegnet til å ivareta befolkningens sikkerhet. (helserevyen.no 22.5.2007)
FDA Issues Safety Alert on Avandia (rosiglitazone) (fda.gov)
Google Trends (Avandia)
Lege sa at legemiddelprodusent forsøkte å kneble hans kritikk av Avandia (nytimes.com 2.6.2007)
Diabetesekspert anklager legemiddelfirmaer for "trusler" (BMJ 2007;335:1113 (1 December))
Avandia (rosiglitazone) - informasjon versus kunnskap og visdom - hvem visste hva?
FDA bedömer Avandia som säkert
lakemedelsvarlden.se 26.11.2013
Den amerikanska läkemedelsmyndigheten har beslutat att lätta på restriktionerna för diabetesmedlet Avandia. (...)
Om GSK, som marknadsför Avandia, skulle vilja nå ut på den europeiska marknaden igen krävs det att de lämnar in en ny ansökan till EMA eller någon nationell myndighet.
- När ett läkemedel har suspenderats är det upp till företagen om de vill ansöka igen, det är inte myndigheten själv som tar initiativet, säger Karl Mikael Kälkner, klinisk utredare på Läkemedelsverket.
Han säger också att det med största sannolikhet skulle krävas nya studiedata om EMA skulle godkänna ett läkemedel som man en gång dragit in på grund av att riskerna bedömts vara större än nyttan. (...)
(Anm: Statlig legemiddelkontroll (Statens legemiddelverk etc.) (mintankesmie.no).)
(Anm: Statlig hvitvasking av legemiddelinformasjon (Tidsskr Nor Legeforen 2010; 130:368 (25.2.2010).)
(Anm: 7. The U.S. Government Accountability Office (GAO). Drug safety: FDA has begun efforts to enhance postmarket safety, but additional actions are needed. GAO-10–68. (27.1.2010).)
- Hvidvask er en global udfordring. (- Årligt hvidvaskes mellem 2 og 5 pct. af det globale bruttonationalprodukt.) (- Det vil i runde tal sige et sted mellem 5 og 13 billioner kroner.)
(Anm: Hvidvask er en global udfordring. Direktiver kan være nyttige, men det fordrer et tæt globalt samarbejde, hvis hvidvask skal minimeres. (- UNODC – FN’s kontor for narkotika og kriminalitet – anslår, at det beløb, der på verdensplan årligt hvidvaskes, andrager et sted mellem 2 og 5 pct. af det globale bruttonationalprodukt. Det vil i runde tal sige et sted mellem 5 og 13 billioner kroner. (jyllands-posten.dk 7.3.2019).)
- Veiledning til etterlevelse av hvitvaskingsregelverket i eiendomsmeglingsvirksomhet.
(Anm: Veiledning til etterlevelse av hvitvaskingsregelverket i eiendomsmeglingsvirksomhet. Dokumentnummer: 11/2019 Rundskrivet gjelder for: Personer som har tillatelse til å drive eiendomsmegling. Eiendomsmeglingsforetak Advokater som har stilt sikkerhet for å drive eiendomsmeglingsvirksomhet. Rettshjelpere som oppfyller vilkår for å drive eiendomsmeglingsvirksomhet (finanstilsynet.no 2.9.2019).)
- Ny Boligbygg-granskning: Tiet om handel til 24 millioner. (- Selger var en investor han skal ha hatt tette forbindelser til, ifølge ny granskningsrapport.)
(Anm: Ny Boligbygg-granskning: Tiet om handel til 24 millioner. Et halvt år etter at boligkjøpene i Boligbygg var ferdiggransket, ramlet en ny overraskelse ut av skapet: En ung innkjøper hadde betalt tre-fem millioner i overpris for en eiendom. Selger var en investor han skal ha hatt tette forbindelser til, ifølge ny granskningsrapport. (dn.no 3.9.2019).)
- Arbeidslivskrim (I): 172 burde vært avvist, fikk likevel kommunale kontrakter. (- Bedrageri, korrupsjon og hvitvasking.)
(Anm: Arbeidslivskrim (I): 172 burde vært avvist, fikk likevel kommunale kontrakter. (- Bedrageri, korrupsjon og hvitvasking. (…) 172 virksomheter er knyttet til lovbrudd omfattet av første kategori av «skal» avvisningsgrunner. Norske kommuner har i perioden 2013-2018 kjøpt varer og tjenester for tre milliarder av 172 virksomheter som burde vært avvist for forhold knyttet til leverandøren. (anbud365.no 30.1.2020).)
- Frps bestevenner. (- Hva hadde Fremskrittspartiet vært uten hovedstadens journalister?) (- I stedet for å grave blir journalister satt til å følge ‘Spillet’ mellom partiene.)
(Anm: Frps bestevenner. Hva hadde Fremskrittspartiet vært uten hovedstadens journalister? (…) I stedet for å grave blir journalister satt til å følge ‘Spillet’ mellom partiene. I saker som handler om regjeringspartiers rolle og ansvar, forfaller de politiske kommentatorene i våre dominerende medier ofte til en slags kollektiv Toppen Bech (ikke et vondt ord om henne!) med velinformert belæring om hva som var sømmelig kutyme og skikk og bruk for «et regjeringsparti». Så også i Frexit-saken. Slik blir kommentatorene som ikke liker Frp støttespillere for Frp. (manifesttidsskrift.no 22.1.2020).)
(Anm: Undersøkende (gravende) journalistikk (mintankesmie.no).)
(Anm: Habilitet (integritet) (mintankesmie.no).)
- Korrupte lokalpolitikere. Fikk naboen din bygge på huset, mens du fikk avslag? Da bør varsellampene blinke.
(Anm: Korrupte lokalpolitikere. Fikk naboen din bygge på huset, mens du fikk avslag? Da bør varsellampene blinke. Det var nettopp forskjellsbehandling i byggesaker som skapte skandale i Drammen. (…) Korrupsjon er ikke bare bestikkelser i form av penger. (…) Så mye som fire av ti ledere i norske kommuner oppgir at ansatte eller folkevalgte har mottatt urettmessige fordeler. (…) Strafferammen for korrupsjon er opp til ti år, nettopp fordi skadene på samfunnet er så store. (nrk.no 1.8.2019).)
- Tar ikke nok penger fra kriminelle. Kriminalitet skal ikke lønne seg, heter det.
(Anm: Tar ikke nok penger fra kriminelle. Kriminalitet skal ikke lønne seg, heter det. Men deler av Oslo- politiet måtte i fjor gi tilbake mer enn de tok inn i utbytte. Statsadvokaten er skuffet over innsatsen til deler av Oslo politidistrikt når det gjelder å ta pengene til hovedstadens kriminelle. (aftenposten.no 4.8.2019).)
(Anm: Bank, børs og finans (Big Bank). (mintankesmie.no).)
(Anm: Finanstilsynet (tidligere Kredittilsynet) (mintankesmie.no).)
(Anm: Økokrim (økonomisk kriminalitet / miljøkriminalitet). (mintankesmie.no).)
(Anm: Forskning bliver farlig, når de negative resultater glemmes. (…) Nyt dansk studie viser problemet. (...) For få negative resultater leder til falske konklusioner. (…) Manglende negative resultater har kostet liv. (…) Vores model viser, at vi er nødt til at få publiceret mindst 20 procent af de negative resultater, der produceres inden for hvert forskningsfelt, hvis vi skal undgå at lave falske antagelser om videnskabelig fakta. (videnskab.dk 5.1.2017).)
(Anm: Legemiddelindustriens fortjeneste var nesten det dobbelte av utgifter til forskning og utvikling (FoU-utgifter) i 2013, 2014 og 2015. (Pharmaceutical Industry Profits Are Nearly Double R&D Costs in 2013, 2014 and 2015) (…) En primær unnskyldning som legemiddelindustrien bruker for «prisøkning» er de høye kostnadene for forskning og utvikling (FoU) som disse firmaene betaler for å få nye legemidler på markedet. (citizen.org 27.3.2017).)
- Dette skjoldet av patenter beskytter verdens bestselgende legemiddel.
(Anm: Dette skjoldet av patenter beskytter verdens bestselgende legemiddel. (- Produktet med 16 milliarder dollar i årsomsetning. (...) - Det har dessuten vært tilgjengelig i nærmere 15 år. (…) Den virkelige utfordringen var den tilsynelatende ugjennomtrengelige festningen av patenter som AbbVie metodisk har bygget rundt sin verdsatte pengemaskin. (…) Humira, som står for mer enn 60 prosent av AbbVies inntekter har en listepris på mer enn 50 000 dollar per pasient. (bloomberg.com 7.9.2017).)
- Motarbeidet AbbVie konkurranse urettmessig ved å skape en "patent-fortykning" for legemidlet Humira?
(Anm: Did AbbVie unfairly thwart competition by creating a ‘patent thicket’ around its Humira drug? In a little noticed order, a federal judge recently raised the intriguing possibility that a so-called patent thicket — a large number of patents that a drug maker obtains to thwart rivals — might stifle competition if the patents were established as the result of some misbehavior. The order was issued last month in a lawsuit filed by AbbVie (ABBV), which is seeking to prevent Boehringer Ingelheim from marketing a biosimilar version of its Humira rheumatoid arthritis treatment. The medicine generated nearly $12.4 billion in sales last year in the U.S. alone for AbbVie and is protected by dozens of patents, many of which do not expire until 2022. (statnews.com 26.7.2018).)
(Anm: Myten om mediers åpenhet. Hvorfor er virkelig fordomsfri og frisinnet debatt uvanlig? Hvorfor så få nye, uavhengige meningsytrere? Hvorfor møter mediene dem dels med motstand, dels med taushet? (aftenposten.no 7.9.2006).)
(Anm: Er det en reproduserbarhetskrise i vitenskapelig forskning? (Is there a reproducibility crisis in science?) (…) Nyere studier, som undersøkte en rekke publiserte legemiddelstudier, klarte å gjenskape resultatene for mindre enn 25 % av dem - og tilsvarende resultater er blitt funnet i andre vitenskapelige disipliner. Hvordan bekjemper vi denne krisen for vitenskapelig ikke-reproduserbarhet? (ed.ted.com).)
(Anm: Spinn i randomiserte kontrollerte studier (RCT) på angstlegemidler (antidepressiva) med et positivt opprinnelig resultat: en sammenligning av bekymringer uttrykt av den amerikanske legemiddelkontrollen FDA og den publiserte litteratur. (Spin in RCTs of anxiety medication with a positive primary outcome: a comparison of concerns expressed by the US FDA and in the published literature.) BMJ Open. 2017 Mar 29;7(3):e012886.)
(Anm: - Hadde medisinerne på et tidligere tidspunkt hatt et evolusjonært perspektiv på sin medisinering, ville vi ikke vært i den kritiske situasjon vi er kommet i med hensyn til resistens. (aftenposten.no 22.8.2016).)
(Anm: Antibiotika kan gi flere kroniske sykdommer. (…) Folkehelseinstituttet: – Faren er underkommunisert. – Advarslene er høyst betimelige, sier lege og seniorforsker Merete Eggesbø ved Folkehelseinstituttet. (…) Ifølge Blaser viser ny forskning at det er en sammenheng mellom endringen av den naturlige tarmfloraen vår og utvikling av nye sykdommer som fedme, diabetes, astma, (...) Advarslene er høyst betimelige, sier lege og seniorforsker Merete Eggesbø ved Folkehelseinstituttet. (nrk.no 30.10.2016).)
(Anm: Researchers explore link between gut microbiome and nutrition in autism spectrum disorder. (…) Sharon Donovan, a professor of nutrition at the University of Illinois explains that researchers have started to look at more specific disease states and the microbiome. "We are starting to see links with autism, obesity, diabetes, cardiovascular disease, and almost every disease that is looked at. (news-medical.net 28.4.2017).)
(Anm: Researchers discover new mechanism that causes chronic intestinal inflammation. Researchers at the University Medical Center of Johannes Gutenberg University Mainz and the German Research Center for Environmental Health, Helmholtz Zentrum München have discovered that too much of the oncogene Bcl-3 leads to chronic intestinal diseases. They describe in Nature Communications exactly how it throws the immune system off-balance. Chronic intestinal disorders such as ulcerative colitis and Crohn's disease are caused by the body's own immune defense system. (news-medical.net 28.5.2017).)
(Anm: Forsiktighet kreves ved samtidig forskrivning av antibiotika med psykofarmaka hos eldre pasienter. (…) Antibiotika har flere legemiddelinteraksjoner med psykofarmaka som kan føre til bivirkninger eller behandlingssvikt og betydelig øke kostnadene for behandlinger. (dgnews.docguide.com 3.4.2017).)
(Anm: Antibiotika associeras med högre risk för tarmcancer. (…) Det här är första studien som visar på sambandet mellan antibiotikaanvändning och utveckling av adenom i tjock- och ändtarmen. Studien publiceras i den vetenskapliga tidskriften Gut. (…) Resultatet visade att långvarig antibiotikaanvändning tidigare i livet, i åldern 20 till 59 år, hade samband med diagnostiserade adenom. (lakemedelsvarlden.se 5.4.2017.)
(Anm: For mange retningslinjer for behandlinger er skrevet av eksperter med økonomiske konflikter, ifølge studie. (Too many treatment guidelines are written by experts with financial conflicts, study finds.) (statnews.com 22.8.2016).)
(Anm: Alvorlige bivirkninger skjules helt lovlig. Lægemiddelvirksomhederne tegner ikke altid et sandfærdigt billede af den medicin, de har udviklet - hverken over for myndighederne eller i de videnskabelige tidsskrifter. (videnskab.dk 25.1.2011).)
(Anm: Manisk svitsj forårsaket av antidepressiva: en sammenfattende sammenlignende gjennomgang av randomiserte kontrollerte studier og observasjonsstudier Manic switches induced by antidepressants: an umbrella review comparing randomized controlled trials and observational studies.(...) Conclusion. Our results highlight an underestimation of the rates of manic switch under antidepressants in RCTs compared to the rates observed in observational studies. Acta Psychiatrica Scandinavica 2016 (First published: 23 November 2016).)
(Anm: For mange retningslinjer for behandlinger er skrevet av eksperter med økonomiske konflikter, ifølge studie. (Too many treatment guidelines are written by experts with financial conflicts, study finds.) (statnews.com 22.8.2016).)
(Anm: Association of anticholinergic burden with adverse effects in older people with intellectual disabilities: an observational cross-sectional study. Conclusions Older people with intellectual disabilities and with mental health conditions were exposed to high anticholinergic burden. This was associated with daytime dozing and constipation. The British Journal of Psychiatry Dec 2016, 209 (6) 504-510.)
(Anm: New study links autism to mutations in mitochondrial DNA (medicalnewstoday.com 31.10.2016).)
(Anm: Legemiddelfirmaer har inngått forlik om påstander om villeding av leger om overlevelsesdata for kreft. (Drug companies settle claim of misleading doctors on cancer survival data) (- Medisinsk svindel sto for mer enn halvparten av 3,5 milliarder dollar som ble utbetalt i erstatninger i fjor. Vanligvis involverte dette beskyldninger om bestikkelser betalt for å generere falske pasienter eller unødvendige behandlinger og resepter som er belastet Medicare.) BMJ 2016;353:i3361 (Published 15 June 2016).)
(Anm: Gruppe (Transparency International) ber om flere tiltak for å takle korrupsjonen innen legemiddelindustrien. (Group calls for more to be done to tackle corruption in the pharmaceutical industry) (…) På begynnelsen av 2016 har én av 10 korrupsjonsetterforskninger i USA involvert legemiddelfirmaer, hvilket ifølge rapporten er et langt høyere antall saker enn det som involverer banksektoren. BMJ 2016;353:i3099 (Published 02 June 2016).)
(Anm: Gruppesøksmål (massesøksmål) (mintankesmie.no).)
FDA Opens Door to Wider Avandia Prescribing
medpagetoday.com 25.11.2013
The FDA has loosened restrictions on the diabetes drug rosiglitazone (Avandia) -- under fire since 2007 because of potential cardiovascular risks -- and will allow drugmaker GlaxoSmithKline to drop the TIDE trial comparing rosiglitazone to pioglitazone (Actos), the only other thiazolidinedione available. (...)
The Cardiovascular Safety of Diabetes Drugs — Insights from the Rosiglitazone Experience (Hjertesikkerheten for legemidler mot diabetes - innsikt fra erfaringer med rosiglitazon (Avandia))
NEJM 2013 (September 2)
The management of type 2 diabetes has been challenged by uncertainty about possible cardiovascular effects related to treatment intensity and choice of drug. Although the Food and Drug Administration (FDA) considers a decrease in glycated hemoglobin an approvable end point, very intensive glycemic control is associated with increased cardiovascular and all-cause mortality.1 The safety of specific drugs for type 2 diabetes — particularly the thiazolidinediones — has also been questioned. After rosiglitazone had been approved in the United States in 1999 and in Europe in 2000, a highly publicized meta-analysis in 2007 reported a 43% increase in myocardial infarction (P=0.03) and a 64% increase in death from cardiovascular causes (P=0.06).2 This report and subsequent FDA advisory committee reviews led to a boxed warning of myocardial ischemia in 2007 and highly restricted access to rosiglitazone in 2010. In 2010, the FDA placed a full clinical hold on the Thiazolidinedione Intervention with Vitamin D Evaluation (TIDE) trial (ClinicalTrials.gov number, NCT00879970), a large cardiovascular-outcome trial designed to evaluate the benefit of rosiglitazone and pioglitazone as compared with placebo (superiority hypothesis) and the safety of rosiglitazone as compared with pioglitazone (noninferiority hypothesis). In part owing to the rosiglitazone experience, the FDA issued an updated Guidance for Industry in 2008 requiring that preapproval and postapproval studies for all new antidiabetic drugs rule out excess cardiovascular risk, defined as an upper bound of the two-sided 95% confidence interval for major adverse cardiovascular events (MACE) of less than 1.80 and less than 1.30, respectively.3 Regardless of the presence or absence of preclinical or clinical signals of cardiovascular risk, the guidance has been applied broadly to all new diabetes drugs, creating substantial challenges in the drug development and approval process. (...)
- Experter röstade för Avandia
Experter röstade för Avandia
lakemedelsvarlden.se 7.6.2013
FDAs expertpanel röstade för att lätta på restriktionerna för det omdebatterade diabetesläkemedlet Avandia.
Den amerikanska läkemedelsmyndigheten FDA har låtit en expertpanel granska om restriktionerna för GSKs diabetesmedel Avandia (rosiglitazon) ska vara kvar. Avandia avregistrerades i EU hösten 2010 efter att studier visat att preparatet kunde öka risken för hjärninfarkt, hjärtsvikt, stroke och andra biverkningar. I USA fick det vara kvar med rekommendationer om kraftigt begränsad användning.
Efter att en ny analys inte visat någon ökad risk för dessa biverkningar lät FDA en expertpanel granska Avandia i början av juni. Av panelens 26 medlemmar röstade 13 för att lätta på restriktionerna och 7 för att häva dem helt. Fem ville fortsätta med begränsad användning och en expert ville helt avregistrera Avandia från den amerikanska marknaden, skriver Pharma Times.
FDA kommer nu att besluta vad som händer med Avandia på den amerikanska marknaden. Innan restriktionerna behandlades cirka 120 000 patienter i USA med läkemedlet, idag behandlas cirka 3 000. (...)
Avandia's Future Still Bleak?
medpagetoday.com 7.6.2013
An FDA panel recommendation to loosen restrictions on the controversial diabetes drug rosiglitazone (Avandia) isn't likely to affect how -- or whether -- doctors prescribe it, according to experts interviewed by MedPage Today.
Clinicians are wary not only of the agent and its unclear risks of cardiovascular complications, but of the thiazolidinedione (TZD) class in general -- and the fact that several alternatives now exist makes it hard to justify prescribing agents that have clouded safety profiles, they said.
"I think the world has already made its judgment that this is not a safe drug, and changing the labeling a little bit is not going to change its use," Steven Nissen, MD, of the Cleveland Clinic and the most vocal critic of rosiglitazone's risks, told MedPage Today. (...)
FDA panel backs less restrictions on GSK's Avandia
pharmatimes.com 7.6.2013
The majority of members on a US Food and Drug Administration advisory panel have recommended modifying the restrictions placed on GlaxoSmithKline's controversial diabetes drug Avandia.
In the latest chapter of the long-running saga surrounding Avandia (rosiglitazone), an FDA joint advisory committee voted to continue to make the drug available to appropriate patients with the majority of the 26 members voting to either modify (13 votes) or remove (7) the strict risk evaluation and mitigation strategy (REMS) programme currently in place on the drug. Five panellists voted to continue with the REMS, while one called for a complete withdrawal from the US market. (...)
FDA genoptager omstridt diabetessag
medwatch.dk 6.6.2013
Det skandaleombruste diabetesmiddel, Avandia, som tidligere var en blockbuster for selskabet GlaxoSmithKline, men blev fjernet fra markedet i Europa og blev underlagt salgsrestriktioner i USA i 2010 pga. sikkerhedsbekymringer, skal nu endnu engang undersøges af amerikanske FDA.
Det sker, fordi en ny undersøgelse af lægemidlet foretaget af Duke Clinical Research Institute (DCRI) giver fornyet opbakning til GSKs egne sikkerhedsstudier med diabetesmedicinen.
Derfor har FDA besluttet at kigge på de kliniske data for midlet endnu engang i de kommende dage, og det kan i sidste ende føre til, at salgsrestriktionerne bliver ophævet, skriver Reuters. Dette scenarie er dog noget usandsynligt, og selv hvis det skulle ske, har GSK ingen planer om at begynde markedsføring af produktet på ny, afslører koncernen. . (...)
Tilbageholder data
FDA medgiver, at den nye undersøgelse fra Duke University bakker op om GSKs data for Avandia, men påpeger at en række mindre studier har sået tvivl om den kardiovaskulære sikkerhed ved medicinen.
Og dr. Thomas Marciniak, som står i spidsen for FDAs Division of Cardiovascular and Renal Products, har advaret medlemmerne af det FDA-panel, som skal tage stilling i sagen, om, at Duke-undersøgelsen ikke kan anses som uafhængig.
Således er studiet både finansieret og foretaget i samarbejde med medicinalkoncernen, som ligeledes har betalt tusindvis af dollars til hovedforskeren bag undersøgelsen, siger Thomas Marciniak ifølge Reuters. Samtidig forklarer han, at GSK ikke har udleveret alle data på Avandia til myndighederne. (...)
(Anm: Pasientsikkerhet (rettssikkerhet) (mintankesmie.no).)
(Anm: Fri tilgang til forskningsresultater? (forskningsdata) (mintankesmie.no).)
(Anm: The hidden side of clinical trials | Sile Lane | TEDxMadrid (youtube.com).)
(Anm: Is Your Doctor in Denial? (Nekter din lege å erkjenne fakta?) Undersøkelse viser at leger ofte avviser klager om legemidlers bivirkninger (Survey Finds Physicians Often Dismiss Complaints About Drugs' Side Effects) (washingtonpost.com 28.8.2007).)
(Anm: Forvaltningsmakt og kunnskapspolitikk. Sammendrag. Helse- og omsorgsdepartementet benekter at de ønsker å styre forskninga i underliggende etater, og ser ingen problemer med at forskninga ligger under forvaltninga. Rus & Samfunn 05 / 2016 (Volum 9) Side: 33-35.)
(Anm: Frie forskere eller maktens lakeier? Abstrakt. Det går et skisma gjennom den samfunnsvitenskapelige rusforskningen. Ved første øyekast er det vanskelig å forstå hvorfor. Rus & Samfunn 05 / 2016 (Volum 9) Side: 36-40.)
(Anm: Nesten halvparten av alle studier som er gjennomført av store sponsorer i det siste tiåret er upublisert (Nearly half of all trials run by major sponsors in past decade are unpublished.) BMJ 2016;355:i5955 (Published 04 November 2016).)
(Anm: Who's not sharing their trial results? (trialstracker.ebmdatalab.net).)
(Anm: Transparency for patients: How much is too much? (pharmafile.com 11.10.2016).)
FDA Panel Starts to Tackle Avandia Safety
medpagetoday.com 5.6.2013
SILVER SPRING, Md. -- A controversial study of the cardiovascular safety of one-time diabetes blockbuster rosiglitazone (Avandia) has proven difficult for FDA and independent reviewers to reanalyze, multiple speakers said here Wednesday.
Because of those struggles, there is little new information available from re-adjudicating a 4,400-patient trial 3 years after the FDA greatly restricted rosiglitazone's label and distribution channels. (...)
Concerns about increased cardiovascular (CV) death, myocardial infarction (MI), and stroke caused the FDA in 2010 to place so many restrictions on prescribing that the number of patients taking the drug fell from more than 117,000 to 3,400. Other countries took the drug off the market altogether.
But Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, requested a re-adjudication of the RECORD study -- the safety study backing rosiglitazone and sponsored by manufacturer GlaxoSmithKline (GSK) -- before making a decision to pull the drug from the market entirely.
This week's 2-day panel is a direct result of Woodcock, who went against the majority opinion of a 2010 advisory panel and the FDA's Office of New Drugs to allow rosiglitazone to remain available -- but only to patients already taking it or to those who have failed other anti-glycemic drugs. GSK was also forced to place rosiglitazone-containing products under a risk evaluation and mitigation strategy (REMS) which includes a MedGuide and elements to assure safe use. (...)
FDA panel revisits Avandia; likely too late for diabetes drug
reuters.com 5.6.2013
Reuters) - A panel of medical advisers to the U.S. Food and Drug Administration will revive a six-year-old debate over the safety of GlaxoSmithKline Plc's Avandia diabetes drug, but the two-day meeting that starts on Wednesday is not expected to greatly boost sales of the onetime blockbuster product. (...)
FDA Reviewing Heart Risks of Glaxo Diabetes Pill
pharmatimes.com 12.4.2013
The Food and Drug Administration will hold a meeting in June to reassess the safety of GlaxoSmithKline's former blockbuster drug Avandia, which was severely restricted in 2010 due to concerns about its impact on the heart.
Regulators announced the highly unusual move in a government notice published on Friday. The FDA said it will ask a panel of outside experts to review a new analysis of the key study examining Avandia's heart risks. (...)
A spokeswoman for Glaxo said the drug company commissioned researchers at Duke University to reanalyze the study, called RECORD, which followed patients for five years and tracked rates of heart attack, stroke and death. The new analysis "did not show a statistically significant difference," in heart safety between Avandia and older diabetes drugs, according to company spokeswoman Mary Anne Rhyne. (...)
Presumably, the FDA could loosen restrictions on the drug if new evidence suggests it is not as dangerous as previously thought. (...)
GSK fights compensation claims from UK patients who took rosiglitazone (GSK kjemper mot erstatningskrav fra britiske pasienter som tok rosiglitazon (Avandia))
BMJ 2013;346:f695 (1 February)
Det britiske multinasjonale firmaet GlaxoSmithKline, som produserer diabeteslegemidlet rosiglitazon (markedsført som Avandia), kjemper mot erstatningskrav fra britiske pasienter som hevder at legemidlet skadet dem, selv om selskapet allerede har betalt milliarder av dollar for å forlike titusenvis av lignende krav i USA. (...) (GlaxoSmithKline, the UK based multinational that makes the antidiabetes drug rosiglitazone (marketed as Avandia), is fighting compensation claims from UK patients who allege that the drug harmed them, even though the company has already paid billions of dollars to settle tens of thousands of similar claims in the United States.)
Families face battle with GSK over dangerous diabetes drug (Familier kjemper mot GSK over farlig diabeteslegemiddel)
guardian.co.uk 29.1.2013
Exclusive: Pharmaceutical giant resists claims despite settlement with victims in US
GlaxoSmithKline has agreed to payouts in US lawsuits alleging Avandia pills could cause heart attacks.
Thousands of families in the UK could be deprived of compensation for the death or harm of a relative caused by the diabetes drug Avandia, even though the British maker has agreed to pay billions of dollars to settle similar claims in the US.
The licence for Avandia was revoked in Europe, in September 2010, because of evidence that it could cause heart failure and heart attacks. The drug can still be prescribed in the US, but not to patients at risk of heart problems. (...)
As drug industry’s influence over research grows, so does the potential for bias (Idet legemiddelindustriens innflytelse over forskningen vokser, øker også potensialet for bias)
washingtonpost.com 25.11.2012
(Dustin Franz/ FOR THE WASHINGTON POST ) - Steven Nissen, a heart specialist at The Cleveland Clinic, has linked pharmaceutical drugs such as Vioxx and Avandia with high cardiovascular risks in patients.
For drugmaker GlaxoSmithKline, the 17-page article in the New England Journal of Medicine represented a coup.
The 2006 report described a trial that compared three diabetes drugs and concluded that Avandia, the company’s new drug, performed best.
The connections between article authors and pharmaceutical companies.
“We now have clear evidence from a large international study that the initial use of [Avandia] is more effective than standard therapies,” a senior vice president of GlaxoSmithKline, Lawson Macartney, said in a news release.
What only careful readers of the article would have gleaned is the extent of the financial connections between the drugmaker and the research. The trial had been funded by GlaxoSmithKline, and each of the 11 authors had received money from the company. Four were employees and held company stock. The other seven were academic experts who had received grants or consultant fees from the firm.
Whether these ties altered the report on Avandia may be impossible for readers to know. But while sorting through the data from more than 4,000 patients, the investigators missed hints of a danger that, when fully realized four years later, would lead to Avandia’s virtual disappearance from the United States:
The drug raised the risk of heart attacks.
“If you looked closely at the data that was out there, you could see warning signs,” said Steven E. Nissen, a Cleveland Clinic cardiologist who issued one of the earliest warnings about the drug. “But they were overlooked.”
A Food and Drug Administration scientist later estimated that the drug had been associated with 83,000 heart attacks and deaths.
Arguably the most prestigious medical journal in the world, the New England Journal of Medicine regularly features articles over which pharmaceutical companies and their employees can exert significant influence. (...)
Association Between Longer Therapy With Thiazolidinediones and Risk of Bladder Cancer: A Cohort Study (Sammenheng mellom lengre behandling med tiazolidindioner og risiko for blærekreft: En kohortundersøkelse)
JNCI J Natl Cancer Inst 2012;104(18):1411-1421
(...)
Background The use of pioglitazone, a thiazolidinedione (TZD), may increase the risk of bladder cancer in patients with type 2 diabetes. In this study, we assessed the risk of bladder cancer associated with the use of TZDs and between pioglitazone and rosiglitazone, an alternative TZD. (...)
Conclusion Long-term TZD therapy (≥5 years) in patients with type 2 diabetes may be associated with an increased risk of bladder cancer, which may be common to all TZDs. (...)
(Anm: Thiazolidinedione; The thiazolidinediones (/θaɪ.əˌzoʊlɨdiːnˈdaɪ.oʊn/), also known as glitazones, are a class of medications used in the treatment of diabetes mellitus type 2. They were introduced in the late 1990s. (en.wikipedia.org).)
(Anm: Pioglitazone-containing medicines: drug safety communication — updated FDA review, increased risk of bladder cancer. ISSUE: As a result of an updated review, the FDA has concluded that use of the type 2 diabetes medicine pioglitazone (Actos, Actoplus Met, Actoplus Met XR, Duetact, Oseni) may be linked to an increased risk of bladder cancer. The labels of pioglitazone-containing medicines already contain warnings about this risk, and FDA has approved label updates to describe the additional studies reviewed. See the FDA Drug Safety Communication for more details, including a data summary. (pharmpro.com 13.12.2016).)
Diabetics sue drugs giant GlaxoSmithKline over heart risk (Diabetikere saksøker legemiddelgiganten GlaxoSmithKline over hjerterisiko)
dailyrecord.co.uk 15.7.2012
Skotske diabetikere er saksøker legemiddelgigant etter at de utbetalte 3 milliarder dollar til amerikanske ofre. (SCOTTISH diabetics are suing a drugs giant after they made a $3billion payout to US victims.)
Forrige uke fikk GlaxoSmithKline rekordstor straffe- og sivilrettslig bot i forbindelse med tre omstridte legemidler inkludert Avandia, som nå er forbudt i Europa. (Last week, GlaxoSmithKline were hit with the record criminal and civil fine in connection with three controversial drugs including Avandia, which is now banned in Europe.)
Den britiske firmaet innrømmet at de unnlot å rapportere sikkerhetsproblemer for diabeteslegemiddel som øker risikoen for hjerteinfarkt. (...) (The UK firm admitted they failed to report safety issues with the diabetes medication, which increases the risk of heart attacks.)
FDA places more restrictions on GSK's Avandia (FDA innfører flere restriksjoner på GSKs Avavdia)
pharmatimes.com 20.5.2011
GlaxoSmithKline's Avandia will not be available in US pharmacies from the middle of November after the Food and Drug Administration imposed further restrictions on the controversial diabetes drug. (...)
GSK's Avandia linked with heart risk again (GSKs Avandia igjen linket til hjerterisiko)
pharmatimes.com 18.3.2011
Sales of GSK's franchise - comprised of Avandia (rosiglitazone), Avandamet (rosiglitazone/metformin) and Avaglim (rosiglitazone/glimepride) - were suspended in Europe last September and its use across the Atlantic was severely restricted amid claims the drug is associated with fluid retention and increased risk of heart failure, and the company is facing a string of liability cases as a result. (...)
Researchers from the US and Europe looked at studies involving more than 810,000 patients, and found, that compared with Actos, Avandia was associated with a significant hike in the risk of heart attack (16%), congestive heart failure (23%), and mortality (14%).
This, the authors note, could lead to 170 excess heart attacks, 649 excess cases of heart failure, and 431 excess deaths for every 100,000 patients given Avandia instead of Actos, which, given that around 3.8 million scripts for the former are dished out every year in the US, could have a "considerable" effect on public health.
GSK stands behind Avandia
However, a spokesperson for GSK told PharmaTimes World News that many of the 16 observational studies included in this meta-analysis have already been looked at by the FDA, which actually "strongly recommended against 'combining' dissimilar observational studies into one estimate, as was done in this meta-analysis". (...)
GSK said it stands behind the safety and efficacy of Avandia when used appropriately. "Since 2007, results from six randomized clinical trials with data related to the cardiovascular safety of Avandia have been reported. Taken together, these trials showed that Avandia does not increase the overall risk of heart attack, stroke or death", it points out. (...)
Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies
BMJ 2011; 342:d1309 (17 March)
Objective To determine the comparative effects of the thiazolidinediones (rosiglitazone and pioglitazone) on myocardial infarction, congestive heart failure, and mortality in patients with type 2 diabetes. (...)
Conclusion Among patients with type 2 diabetes, use of rosiglitazone is associated with significantly higher odds of congestive heart failure, myocardial infarction, and death relative to pioglitazone in real world settings. (...)
Glaxo Takes $3.4 Billion Charge on Legal Problems
nytimes.com 17.1.2011
The British drug maker, GlaxoSmithKline, announced Monday that it was setting aside $3.4 billion to pay for United States government investigations and for product liability cases over its marketing of the diabetes drug Avandia in the face of heart attack risks.
The one-time charge is expected to wipe out its fourth-quarter profit, by consensus analyst estimates. GlaxoSmithKline’s European shares fell about 2 percent on the news.
Avandia, once the world’s top-selling diabetes medicine, was severely restricted in September by the Food and Drug Administration and banned by the European Medicines Agency after safety reviews. (...)
GSK regulatory update on Avandia following EMA and FDA reviews
pharmanews.eu.com 27.9.2010
GlaxoSmithKline (GSK) confirms that following a review of Avandia® (rosiglitazone maleate) by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), each agency has announced their individual regulatory decisions and the resulting actions. In the European Union*, the EMA has suspended the marketing authorisation for all rosiglitazone-containing medicines (Avandia, Avandamet® and Avaglim®). (...)
Financial Information
Total sales of Avandia products in the first half of 2010 were £321m (-18%); US £164m (-23%); Europe £72m (-17%); Emerging Markets £37m (-5%); RoW £48m (-6%)**. As a result of the regulatory updates in both the US and EU, GSK now expects global sales of Avandia products to be in a range of approximately £100m - £150m in the second half of 2010 and with minimal annual sales thereafter. These estimates are net of customer returns of product previously sold. Associated one-off costs in 2010 comprising stock write-offs, asset write-offs and other related one-off costs are currently expected to be approximately £100m on a pre-tax basis.
To access the full EMA announcement visit www.ema.europa.eu.
To access the full FDA announcement visit www.fda.gov. (...)
Avandia: Reaction and implications (Avandia: reaksjoner og konsekvenser)
pharmatimes.com 24.9.2010
Following the regulators' moves against GlaxoSmithKline's Avandia, industry observers have been reacting to the news and considering the impact of suspension in Europe and further restrictions in the USA. (...)
Dr Wolfe went on to say that more than three years ago at an FDA advisory committee meeting, Public Citizen urged the FDA to ban Avandia. "Since then, 9 million prescriptions for the drug have been filled in the USA. This means that, just in the past three years alone, tens of thousands more patients have needlessly suffered hospitalisations for heart failure or deaths" than would have had they taken Takeda's Actos (pioglitazone), "a comparable, but safer drug". (...)
Rødt kort til medicin mod sukkersyge
berlingske.dk 24.9.2010
Landets læger får i dag en anbefaling fra Lægemiddelstyrelsen om ikke længere at ordinere tre midler mod sukkersyge. (...)
Suspenderer diabetesmedisin
nrk.no 24.9.2010
Avandia er én av medisinene som suspenderes. Årsaken er at virkestoffet rosiglitason gir økt risiko for hjerte- og karsykdommer. I Norge har myndighetene fått to rapporter om hjertesykdom som følge av medisinbruken. (...)
Nitten rapporter om bivirkninger i Norge
Det er rundt 6500 nordmenn som bruker denne medisinen. Norske myndigheter har fått inn 19 rapporter om bivirkninger, av disse er to hjerte- og karrelaterte.
– Disse midlene suspenderes fordi de det ser ut som de gir litt økning i risiko for hjerte- og karsykdommer. Vi ser at fordelen ved blodsukkersenkningen ikke er stor nok til å forsvare økningen i risiko, sier Kjetil Retterstøl, overlege ved avdeling for legemiddelutredning ved Statens legemiddelverk. (...)
A timeline of regulatory milestones for GlaxoSmithKline's diabetes pill Avandia
latimes.com 23.9.2010
(...) Here are some key events in the drug's history.
—May 1999: The Food and Drug Administration approves GlaxoSmithKline's drug Avandia based on studies showing it helps control blood sugar levels.
—June 2003: GlaxoSmithKline publishes study results claiming that Avandia has benefits for the heart.
—May 2007: Dr. Steven Nissen of the Cleveland Clinic publishes medical journal article estimating that patients taking Avandia were 43 percent more likely to experience heart attack than those taking other diabetes drugs or no diabetes medication. (...)
—June 2003: GlaxoSmithKline publishes study results claiming that Avandia has benefits for the heart.
—May 2007: Dr. Steven Nissen of the Cleveland Clinic publishes medical journal article estimating that patients taking Avandia were 43 percent more likely to experience heart attack than those taking other diabetes drugs or no diabetes medication.
—July 2007: A panel of FDA advisers votes 22-1 against recommending removing Avandia from the market, saying evidence the widely used drug was risky to the heart wasn't conclusive enough to merit such drastic action.
—November 2007: The FDA adds an unusual warning label to Avandia saying that the evidence is "inconclusive" on whether the drug increases heart attack risk.
—February 2010: A report by the Senate Finance Committee concludes that GlaxoSmithKline had full knowledge of the heart risks of its drug in late 2004 or early 2005. The report prompts a new round of scrutiny of Avandia's safety.
—June 2010: FDA scientist Dr. David Graham publishes a paper estimating Avandia has caused as many as 100,000 heart attacks, strokes, deaths and cases of heart failure in the U.S. He urges the FDA to withdraw the drug.
—July 2010: A 33-member panel of FDA experts votes 20-12 to keep Avandia available in the U.S. Of the 20 who voted to keep it on the market, half say it should only be available on a limited basis.
—Sept. 23, 2010: FDA announces major restrictions on which patients can get Avandia, while European regulators order it off the market. Both decisions were based on heart attack risks. (...)
Diabetesmidlene Avandia, Avandamet og Avaglim suspenderes
legemiddelverket.no 23.9.2010
Diabetesmidlene Avandia, Avandamet og Avaglim inneholder virkestoffet rosiglitason og blir suspendert i EØS-området etter anbefalinger fra den vitenskapelige komiteen til det europeiske legemiddelkontoret. Norge er representert i denne komiteen
Bakgrunnen for suspensjonen er at rosiglitason synes å gi økt risiko for hjerte-karsykdom slik at fordelene med behandlingen ikke oppveier risikoen. Suspensjonen blir permanent dersom det ikke kommer nye data som endrer nytte-risikovurderingen. Anbefalingene om suspensjon er sendt til Europakommisjonen for å fatte et juridisk bindende vedtak. (...)
EU pulls plug on Glaxo's Avandia, FDA restricts (EU fjerner Glaxos Avandia, FDA begrenser bruken)
reuters.com 23.9.2010
LONDON/WASHINGTON (Reuters) - European officials moved to pull GlaxoSmithKline's diabetes drug Avandia off the market and U.S. authorities imposed tight restrictions over heart risks, effectively spelling the commercial end to the once-lucrative medicine. (...)
Regulators Impose Tight Restrictions on Diabetes Drug (Tilsynsmyndigheter innfører sterke restriksjoner på diabeteslegemiddel)
nytimes.com 23.9.2010
WASHINGTON — In a highly unusual coordinated announcement, drug regulators in Europe and the United States said Thursday that Avandia, the controversial diabetes medicine, will no longer be widely available.
The drug’s sales will be suspended entirely in Europe, while patients in the United States will be allowed access to the medicine only if they and their doctors attest that they have tried every other diabetes medicine and that patients have been made aware of the drug’s substantial risks to the heart. (...)
EU, U.S. regulators set to rule on Glaxo's Avandia (EU og amerikanske tilsynsmyndigheter avsier kjennelse for Avandia)
reuters.com 23.9.2010
(Reuters) - European and U.S. drugs regulators will both issue statements on Thursday on whether GlaxoSmithKline's diabetes drug Avandia should be pulled from the market due to concerns about heart risks.
The European Medicines Agency (EMA) in London and U.S. Food and Drug Administration in Washington both said they would publish their decisions at 1530 GMT, and follow up with separate conference calls for reporters.
A spokeswoman for the EMA said she could not say whether the two agencies were likely to come to the same conclusion on the drug.
"We are making our own statement, and then they will do theirs," she said.
Avandia, once Glaxo's second-biggest selling drug, is under safety review in its two biggest markets after heart attack concerns were raised by U.S. researchers in 2007. (...)
MHRA under pressure to withdraw rosiglitazone (MHRA under press for å trekke Avandia (rosiglitazone))
pulsetoday.co.uk 7.9.2010
The UK drug regulator has come under fire for failing to act on an expert recommendation to withdraw the type 2 diabetes drug rosiglitazone.
A Freedom of Information Act request by the BMJ has uncovered a report from July from the Commission on Human Medicines, an advisory group to the Medicines and Healthcare Products Regulatory Agency, saying the drug’s risks ‘outweigh its benefits and it no longer has a place on the UK market.’ (...)
Rosiglitazone: what went wrong? (Avandia (rosiglitazone): hva gikk galt?)
BMJ 2010; 341 (6 September)
(...) The FDA meeting was held in the open, in front of a packed audience including the world’s media. Ahead of the meeting, the FDA published the 765 page report circulated to panel members.
This is far removed from the secrecy shrouding proceedings at Europe’s regulator, the EMA. The BMJ has talked to a range of experts close to the European regulatory process and submitted a series of Freedom of Information requests to the EMA, but we still have no clear picture of why, after initial rejection in October 1999, the EMA gave market authorisation to rosiglitazone in July 2000 in the absence of new evidence. Neither have doctors and patients been told that in July the UK’s Commission on Human Medicines— in an unanimous vote— advised the Medicines and Healthcare products Regulatory Agency (MHRA) to withdraw the drug. In a statement, the MHRA has confirmed that the evidence now suggests that the risks associated with rosiglitazone outweigh the benefits and “that it no longer has a place on the UK market.” But a “dear doctor” letter sent to UK doctors in July advised doctors to “consider alternative treatments where appropriate.”2 The MHRA said that it used the information provided by the Commission on Human Medicines to push for a UK withdrawal as part of the Europe-wide review by the European Medicines Agency. (...)
COMMENT by ALEX BRUMMER: Glaxo back in the firing line
dailymail.co.uk 7.9.2010
When Glaxo took a charge of just over £1billion in July, in an effort to close down Avandia as an issue for the financial markets (if not the diabetes patients), it must have hoped to draw a line under the disputed side-effects of the drug.
Now the British authorities have come back and bitten the pharmaceutical giant on the bottom.
The alleged problems of Avandia are proving every bit as damaging to its reputation as depression drug Seroxat (sold as Paxil in the US) was when it hit the headlines in 2004. (...)
UK wants GSK's Avandia pulled as EU reviews safety (Storbritannia ønsker ar GSKs Avandia trekkes fra markedet idet EU gjennomgår sikkerhet)
reuters.com 3.9.2010
The strong line from safety experts in the drugmaker's home market is a fresh blow to a medicine that was once Glaxo's second biggest seller but has become a liability since being linked to increased heart attack risk in 2007.
The Medicines and Healthcare products Regulatory Agency (MHRA) said it believed the risks of Avandia, known generically as rosiglitazone, outweighed its benefits and that "it no longer has a place on the UK market." (...)
Avandia warning signs seen online as early as '04 (Varselsignaler for Avandia så tidlig som 2004)
mmm-online.com 31.8.2010
A new report says patients began discussing the risks of GlaxoSmithKline diabetes drug Avandia in online forums and blogs well before a meta-analysis linked it to higher heart-attack risk. Neither physicians nor company officials acknowledged their worries, contributing to an alarming drop in patient sentiment and, according to authors, a lost opportunity to reach out and restore trust. (...)
Kritik mot information om Avandia
lakemedelsvarlden.se 24.8.2010
Både den europeiska läkemedelsmyndigheten EMA och amerikanska FDA håller på var sitt håll att granska diabetesmedlet Avandia då nya data visarytterligare att läkemedlet kan öka risken för stroke och hjärtinfarkt. Nu får tillverkaren Glaxosmithkline kritik för att inte varna om riskerna med en pågående studie med läkemedlet. (...)
Det är inte första gången det blåser snålt kring Avandia och dess säkerhetsprofil. Anklagelser om spökskrivna artiklar och undanhållande av biverkningsdata har figurerat sedan ett par år. Nyligen hade amerikanska Time en artikel som ifrågasätter FDA:s hanterande av hela godkännandeprocessen av läkemedlet. (...)
Glaxo Memo on Avandia Is Questioned (Stiller spørsmål ved Glaxos Avandia-notat)
nytimes.com 19.8.2010
Federal drug regulators ordered GlaxoSmithKline to send a letter to crucial doctors describing a hearing in July where an expert advisory panel discussed the risks of Avandia, the company’s controversial diabetes medicine. (...)
After Avandia: Does the FDA Have a Drug Problem? (Etter Avandia: Har FDA et legemiddelproblem?)
time.com 12.8.2010
Five days before a 2007 article in the New England Journal of Medicine showed that the diabetes drug Avandia was linked to a 43% increase in heart attacks compared with other medications or placebos, a group of scientists and executives from the drug's maker, GlaxoSmithKline (GSK), gathered in a conference room at the offices of the Food and Drug Administration in White Oak, Md. The GSK goal: to convince regulators that the evidence that the company's $3 billion-a-year blockbuster drug caused heart problems was inconclusive. To do that, the GSK officials focused not on heart-attack data but on a broader, less well defined category of heart problems called myocardial ischemia. The most recent studies of Avandia, the GSK officials told the FDA, had "yielded information that is inconsistent with an increased risk of myocardial ischemic events," according to sealed court proceedings obtained by TIME. (...)
GlaxoSmithKline to Pay $460 Million to Avandia Plaintiffs (GlaxoSmithKline utbetaler 460 millioner dollar til Avandia-saksøkere)
lawyersandsettlements.com 28.7.2010
Philadelphia, PA: GlaxoSmithKline has reportedly agreed to pay $460 million to settle lawsuits alleging that diabetes medication Avandia caused an increased risk of heart attacks. News of the settlement comes as the US Food and Drug Adminstration (FDA) held an advisory panel to discuss Avandia side effects and determine what action, if any, to take on the drug. (...)
FDA Panel Grants Avandia a Reprieve (FDA-panet gir Avandia en utsettelse)
online.wsj.com 14.7.2010
A Food and Drug Administration advisory panel voted Wednesday to recommend allowing sales of the diabetes drug Avandia to continue, but said the drug poses a "significant safety" concern because it raises the risk of heart attacks. (...)
Janet Woodcock, the head of the FDA's drug division, said the agency will make a final decision soon and will take the committee's vote into consideration. (...)
The advisory committee voted overwhelmingly Wednesday that Avandia posed a higher heart attack risk than Actos, which is made by Takeda Pharmaceutical Co. (...)
Former FDA Commissioner David Kessler said the Avandia controversy "will chart the future direction of the agency on drug safety," and result in more time and money spent by companies getting drugs approved, and "more safety for the consumer."
Dr. Kessler noted the recall of the painkiller Vioxx in 2004, which was, like Avandia, linked to serious heart problems after it was on the market. "Vioxx and Avandia together have shown the agency and industry that they need to address serious, but common adverse events" before approval. (...)
Grassley Says Glaxo Withheld Drug Data (Grassley sier Glaxo hemmeligholdt legemiddeldata)
online.wsj.com 13.7.2010
WASHINGTON—A former Food and Drug Administration official said the maker of diabetes drug Avandia withheld from regulators information suggesting the drug posed an increased risk for serious heart problems, according to people familiar with her statements.
The allegation comes as one of the biggest recent drug-safety fights nears a climax. Starting Tuesday, a panel of FDA experts will debate whether GlaxoSmithKline PLC's Avandia should be pulled from the market after years of controversy over its alleged side effects.
The statements by the ex-FDA official, made in a deposition for lawsuits filed against Glaxo, are included in a letter received Monday by the agency from Sen. Charles Grassley (R., Iowa), the top Republican on the Senate Finance Committee, which has been investigating Glaxo and Avandia. His letter, co-signed by committee chairman Sen. Max Baucus (D., Mont.), includes additional information detailing internal company records about Avandia, according to people familiar with the letter. (...)
FDA panel: Diabetes drug should stay on market (FDA-panel: Legemiddel mot diabetes bør være på markedet)
forbes.com 15.7.2010 (Associated Press)
WASHINGTON -- GlaxoSmithKline's drug Avandia should stay on the market, federal health experts voted Wednesday, but the controversial diabetes pill should be subject to new restrictions due to risky heart side effects.
A panel of Food and Drug Administration advisers voted 20-12 to keep the once blockbuster pill available for diabetics. But 10 panelists also called for limiting who can receive and prescribe the much-debated medication.
The vote marks a tough win for British drugmaker Glaxo, which is facing thousands of lawsuits from patients who say Avandia caused their heart attacks or strokes. While the company may fare better in court due to the panel ruling, sales of Avandia are likely to shrink to minuscule levels. (...)
David Graham som vurderer legemidler hos FDA fortalte panelet at Avandias risiko var så reell at "den kan føre til sykehusinnleggelse eller at du møter en tidlig grav". (FDA reviewer David Graham told the panel Avandia's risks were real enough "to put you in a hospital or a cemetery.")
Graham, som ønsker at pillen forbys publiserte nylig en analyse som estimerer at så mange som 100 000 hjerterelaterte problemer kan være forårsaket av Avandia blant seniorer hos Medicare. (...) (Graham, who wants the pill banned, recently published an analysis estimating that as many as 100,000 heart-related problems may have been caused by Avandia among seniors on Medicare.)
Glaxo takes £1.57bn charge for Avandia, Paxil (Glaxo setter av 1,57 milliarder pund for anklager mot Avandia og Seroxat (Paxil))
telegraph.co.uk 15.7.2010
GlaxoSmithKline, the British drug maker, is to take a £1.57bn charge to cover settlements and legal actions relating to its diabetes pill Avandia and antidepressant Paxil.
With respect to Paxil and Avandia, the charge includes provisions for settled cases and an estimate for outstanding cases. Terms of the settlements reached are confidential, Glaxo said. (...)
Medicinalfirma beskyldes for at skjule bivirkninger
business.dk 15.7.2010
GlaxoSmithKline forsøgte angiveligt at skjule alvorlige bivirkninger ved middel mod diabetes 2.
Igennem 11 år har det velkendte medicinalfirma GlaxoSmithKline forsøgt at skjule, at firmaets diabetesmedicin Avandia rent faktisk ikke er bedre end sin nærmeste konkurrent. Samtidig har man forsøgt at sløre, at det kunne være risikabelt for hjertet at tage medicinen, skriver New York Times ifølge Politiken.dk. (...)
Forsker kræver Avandia pillet af markedet
fyens.dk 14.7.2010
Glaxosmithklines diabetesbehandlingspille Avandia burde aldrig have været godkendt af de amerikanske myndigheder. Det konkluderer den forsker, der i 2007 fandt frem til, at der var en forbindelse mellem diabetespillen og hjerteproblemer.
- FDA begik en fejl og missede en masse tidlige signaler. Der er virkelig ingen særlig fordel ved dette medikament. Det burde blive fjernet fra markedet så hurtigt som muligt, siger Steven Nissen til Bloomberg. (...)
Anklage: Medicinalfirma skjulte ubehagelige data
politiken.dk 14.7.2010
GlaxoSmithKline forsøgte angiveligt at skjule alvorlige bivirkninger ved middel mod diabetes 2.
Medicinalfirmaet GlaxoSmithKline (GSK) har i 11 år forsøgt at skjule, at firmaets diabetesmedicin Avandia ikke var bedre end sin nærmeste konkurrent, og at det kunne være risikabelt for hjertet at tage medicinen.
Det skriver New York Times.
LÆS ARTIKEL Hele artiklen fra New York Times (eksternt link - på engelsk)
Risikoen ved Avandia, der bruges mod diabetes type 2, blev første gang offentliggjort i maj 2007, otte år efter at midlet var introduceret på markedet.
Dengang sagde GSK, at firmaet havde kendt til en mulig risiko ved midlet siden 2005. (...)
Ifølge nyhedssitet Bloomberg har GlaxoSmithKline, som er et af verdens største medicinalfirmaer, indvilget i at betale omkring 4,5 milliarder kroner for at bilægge en række søgsmål som følge af helbredsrisikoen ved Avandia. (...)
Avandia Survives FDA Panel, But Just Barely (Avavdia overlever FDA-panel, men bare så vidt)
blogs.forbes.com 14.7.2010
(...) It probably is about as good news as GlaxoSmithKline could have expected. But it is not at all the clear victory that the initial headlines make it sound like. It leaves the tough decision for the full Food and Drug Administration. The most likely scenario is that the drug stays on the market, but only in an extremely limited fashion. (...)
Tags: Avandiapanel (...)
Analysis: Negative Avandia vote may bring new GSK legal woes (Analyse: Negative voteringer mot Avandia kan føre til nye rettslige problemer)
reuters.com 14.7.2010
(Reuters) - A negative ruling in a fateful U.S. regulatory vote on Wednesday over GlaxoSmithKline Plc's Avandia diabetes drug could spark a new wave of litigation and spell more difficulty for the company in court.
A U.S. Food and Drug Administration advisory panel weighing evidence of heart risks with Avandia will recommend whether the drug should be removed from the market, one of five options that include restricting its use or keeping the drug on the market without a heart-attack warning.
Safety concerns over heart risks have engulfed Avandia since 2007, leading to a steep sales decline for the company's one-time second-biggest-selling drug and precipitating a flood of lawsuits. (...)
Avandia stays on the market, GSK to take £1.57 billion charge
pharmatimes.com 15.7.2010
GlaxoSmithKline has grounds to celebrate this morning after a US joint advisory committee voted to allow the diabetes drug Avandia to remain on the market, although the label on the controversial treatment may be revised. (...)
GSK chief medical officer Ellen Strahlman said that following the recommendations, “we will, of course, continue to work with the FDA in the best interest of diabetes patients who face this chronic and serious disease”. She added that “we would like to acknowledge the efforts made by the FDA to apply scientific rigour to the debate and understanding of the benefit-risk profile of Avandia". (...)
Most Avandia lawsuits settled
Just after the vote results were announced, GSK issued a statement saying that it expects to record a £1.57 billion charge in the second quarter which will include the settlement of “the substantial majority of the product liability cases relating to Avandia”.
The company did not specify how much was going to settle the Avandia lawsuits as the charge includes an investigation by the US Government into the company’s former manufacturing site at Cidra, Puerto Rico, as well as product liability and antitrust litigation relating to the antidepressant Paxil (paroxetine). The after-tax cost of the legal charge will be £1.35 billion.
Dan Troy, the company’s general counsel, said the charge “represents a substantial proportion of GSK’s outstanding litigation”. He added that this progress is helping us to reduce financial uncertainty and risk for shareholders”.
Collins Stewart’s Papadakis said the charge is in addition to existing £2.3 billion provisions, adding that “we view this clarity as a significant positive”.(...)
(Anm: Seroxat (Paxil) (paroxetine; paroksetin) (SSRI) (mintankesmie.no).)
(Anm: ACS Publications- søk paroxetine (Seroxat; Paxil etc.) (pubs.acs.org).)
(Anm: ACS Publications- søk sertraline (Zoloft) (pubs.acs.org).)
Avandia: GlaxoSmithKline Cover-Up Turns Off Doctors (GlaxoSmithKline dekkhistorie gjør leger mer tilbakeholdne overfor Avandia)
abcnews.go.com 14.7.2010
In the face of mounting evidence that GlaxoSmithKline withheld important safety data on their controversial drug Avandia, some doctors are abandoning use of this diabetes treatment.
Documents released Tuesday morning by the Senate Finance Committee suggested that for more than a decade, the drugmaker deliberately hid study results showing that Avandia could worsen certain risk factors for heart disease and was no better than its market competitor Actos. (...)
Avandia On Trial: Panel Condemns Avandia
blogs.forbes.com 14.7.2010
With 12 votes to withdraw Avadia and 10 votes to impose severe restrictions, out of 33 total FDA panel votes, Avandia is as good as dead as a commercial product. Only ten panel members voted for milder restrictions or warnings for the drug. Many of the panelists who voted for severe restrictions said they were close to voting for outright withdrawal but were held back merely because the evidence for Avandia causing heart attacks, although bad, was not totally definitive. (...)
Tags: Avandiapanel (...)
F.D.A. Panel Votes to Restrict Avandia
prescriptions.blogs.nytimes.com 14.7.2010
A majority of the advisory panel of the Food and Drug Administration voted today to restrict the sales of Avandia, a controversial diabetes drug, because of its potential risk for causing heart attacks. The 33-member advisory committee was deeply divided. Twelve voted to remove Avandia from the market altogether; 10 for continued sale but with new label revisions and possible restrictions; 7 to add more warnings and 3 for no change at all. But the votes can also be viewed as a decision by a majority, 21, to continue allowing sales of Avandia, with more restrictions. A final decision will be made by the F.D.A. at a later date. (...)
Keep Rosiglitazone on the Market, FDA Panel Says
medpagetoday.com 14.7.2010
(...) Wednesday's vote marks the second time an FDA advisory panel has essentially endorsed rosiglitazone. In 2007, a panel voted that while the drug appears to carry a higher risk of cardiovascular events, it should continued to be marketed.
Since then, concern over the health risks of the drug has continued to grow, so the FDA convened the current panel of diabetes and statistical experts to revisit the issue. The 33-member panel was comprised of the Endocrinology and Metabolic Drugs and the Drug Safety and Risk Management Advisory Committees.
And once again the committee confirmed that it thinks there is a safety risk with the drug, but that rosiglitazone should remain an option for patients with type 2 diabetes.
The FDA does not have to follow the advice of its advisory committees, but it usually does. (...)
Avandia on Trial: The Battle of The Statisticians (Avandia på tiltalebenken: Statistikernes krig)
Robert Langreth is a senior editor at Forbes, in charge of health care coverage
blogs.forbes.com 13.7.2010
Hva skjer når du har et legemiddel som er svært mistenkelig, men ikke skyldig utover rimelig tvil fordi enkelte bevis er motstridende? (What happens when you have a drug that looks very suspect, but isn’t guilty beyond a reasonable doubt because some of the evidence is conflicting?)
Dersom du er FDA så henter du inn en masse statistikere for å debattere spørsmålet ad infinitum (i det uendelige). Det er hva som skjer i dagens møte når et rådgivende panel skal bestemme skjebnen til GlaxoSmithklines Avandia. Det er forvandlet til en sammenkomst for hjernelammende statistisk sjargong, idet antallet guruer i panelet analyserer kvaliteten på ulike mangelfulle forsøk. (If you are the FDA, you bring out a lot of statisticians to debate the matter ad infinitum. That is what is happening at today’s meeting of an advisory panel to determine the fate of GlaxoSmithkline's Avandia. It has turned into a mind-numbing statistics jargon fest, as numbers gurus on the panel parse the quality of various flawed trials.)
Sakens kjerne, dersom man dropper all sjargong: Enkelte studier viser at Avandias er farlig for hjerte mens andre viser at det er nøytralt; bare en håndfull viser at det beskytter. Det er dette mønsteret du finner hos et legemiddel som har en liten men reell risiko for å forårsake hjerteanfall, en risiko som er nær grensen for å kunne oppdages i kliniske studier. (...) (The bottom line if you want to skip all the jargon: Some studies show Avandia is risky for the heart and others show that it is neutrall; only a handful show it is protective. It is the kind of pattern you might find with a drug that has a small but real risk of causing heart attacks, a risk that is close to the detect ion limit of clinical studies.)
Tags: Avandiapanel (...)
(Anm: Avandia (rosiglitazone) - informasjon versus kunnskap og visdom - hvem visste hva? (mintankesmie.no).)
GSK's bitter sweet pill to swallow (GSKs svelger bittersøt pille)
thisismoney.co.uk 13.7.2010
After BP's rough treatment in Washington, GlaxoSmith-Kline, one of Britain's world class pharmaceutical groups, cannot take the current regulatory hearings on its key diabetes drug Avandia lightly.
In much the same way as BP became a victim of the American debate about the advisability of deep-sea drilling for oil, so the food & Drug Administration hearings into Avandia could become something more serious.
One of the few legislative victories for Barack Obama has been healthcare reform. Among the goals of that reform was to cap the cost of pharmaceuticals, which form a large chunk of America's big health bill.
It would be grotesque if GSK - which sought to clear up its act in the wake of the Paxil/Seroxat controversy - were now to be dragged through the mud over Avandia. (...)
Avandia debate spotlights key FDA decision makers
forbes.com 14.7.2010
The Food and Drug Administration typically goes to great lengths to keep its decision-making process out of the public eye. As an agency that handles confidential data from drug companies, FDA staffers are typically barred from speaking out about their work.
But as the agency considers whether to withdraw the troubled diabetes drug Avandia, the public is getting a rare look at some of the personalities within the FDA. (...)
Diabetes Drug Maker Hid Test Data on Risks, Files Indicate (Arkivdata indikerer produsent av legemiddel mot diabetes skjulte data for risiko)
nytimes.com 13.7.2010
By GARDINER HARRIS
In the fall of 1999, the drug giant SmithKline Beecham secretly began a study to find out if its diabetes medicine, Avandia, was safer for the heart than a competing pill, Actos, made by Takeda.
Avandia’s success was crucial to SmithKline, whose labs were otherwise all but barren of new products. But the study’s results, completed that same year, were disastrous. Not only was Avandia no better than Actos, but the study also provided clear signs that it was riskier to the heart.
But instead of publishing the results, the company spent the next 11 years trying to cover them up, according to documents recently obtained by The New York Times. The company did not post the results on its Web site or submit them to federal drug regulators, as is required in most cases by law. (...)
Drugmaker Hid Negative Data on Rosiglitazone (Legemiddelfirma skjulte negative data for rosiglitazone (Avandia))
medpagetoday.com 13.7.2010
WASHINGTON -- GlaxoSmithKline, maker of rosiglitazone (Avandia), hid negative trial results on the controversial diabetes drug more than a decade ago, according to a report released by the Senate Finance Committee.
Rosiglitazone was approved by the FDA in 1999 to treat type 2 diabetes. But "as far back as 2000, internal e-mails show that GSK executives sought to downplay scientific findings, which raised questions about the safety [of the drug]," the committee wrote, citing an internal memo about a trial comparing rosiglitazone to pioglitazone (Actos) that found rosiglitazone presented a "worse lipid profile" than its competitor.
In another e-mail, sent on July 20, 2001, a GlaxoSmithKline executive, discussing the negative data wrote "we would hope that these do not see the light of day."
Controversy over the drug began three years ago when a 2007 meta-analysis of data from 42 clinical trials found a 43% increase in relative risk of myocardial infarction among patients treated with rosiglitazone. (...)
One Sign FDA Could Pull Avandia (Et tegn på at FDA kan fjerne Avandia)
Matthew Herper is a senior editor at Forbes
forbes.com 13.7.2010
One bad sign for Glaxo: The amount of time being given to drug safety researcher David Graham, who played a key role in the controversies over Merck's Vioxx and, before that, Pfizer's Rezulin. For more on Graham, see this profile of him I wrote in 2004 when he was Forbes.com's Face of the Year.
Graham is getting 45 minutes of presentation and discussion, some of it on his "personal views" about a study. His presentation is only halfway through, but already there are some zingers. "If you don't stay on a drug long enough to get benefit, then all you're getting is the risk," he says.
Of the Record trial, the key study run by GlaxoSmithKline, he says, "Why would we use it as something so perfect, so holy, that we would use it to exonerate a drug. You can't trust it. If we do trust it, we're engaging in the willing suspension of disbelief."
As a comment in response to Graham's first questions, Rebecca Gillion, the patient representative on the trial and a diabetic, noted that she had recommended to her mother, a heart patient, that she should not take Avandia. (...)
FDA Staffers Blast Rosiglitazone at Advisory Panel Meeting
medpagetoday.com 13.7.2010
GAITHERSBURG, Md. -- The two major FDA critics of rosiglitazone (Avandia) again denounced the diabetes drug during the first day of an advisory committee meeting that will end with a vote on whether the agency should pull it from the market. (...)
Avandia On Trial: The FDA Counterpoint
blogs.forbes.com 13.7.2010
The FDA panel meeting over the future of GlaxoSmithKlines' diabetes drug Avandia is in an after-lunch slow period after a heated morning. But a few things that are happening may provide clues to the thinking of some members of the panel.
The main presentations after lunch--by Kate Mahoney, an FDA clinical reviewer, and David Hoberman, an FDA statistician--amount to a defense of GlaxoSmithKline's one big safety study of the drug. They counter the critics from the FDA and academia this morning who argued that this trial is close to worthless. (...)
Tags: Avandiapanel (...)
Glaxo to pay $460 million in Avandia settlement – report
reuters.com 13.7.2010
(Reuters) - GlaxoSmithKline Plc (GSK.L) has agreed to pay about $460 million (303.5 million pounds) to resolve a majority of the lawsuits alleging its Avandia diabetes drug caused heart attacks and strokes, Bloomberg News reported on Tuesday.
Glaxo has agreed to settle about 10,000 cases at an average of at least $46,000 each, the report said, citing unnamed sources.
Analysts estimate the drugmaker faces about 13,000 Avandia lawsuits alleging personal injuries. (...)
Take Rosiglitazone Off the Market, Says FDA Staff (Fjern Rosiglitazone fra markedet, sier FDA-ansatte)
medpagetoday.com 9.7.2010
WASHINGTON -- Rosiglitazone (Avandia) should be pulled from the market because of the "serious" cardiovascular risk the diabetes drug poses, which exceeds that of competitor pioglitazone (Actos), according to FDA staff reviewers. (...)
GSK backs Avandia again amid renewed pressure for withdrawal (GSK støtter nok engang Avandia til tross fornyet press om tilbaketrekning fra markedet)
pharmatimes.com 29.6.2010
A fortnight ahead of a full-on review by US regulators, GlaxoSmithKline’s Avandia is again at the centre of controversy with the release of data from three studies, two of which are negative while the third shows that the diabetes drug appears to be safe. (...)
Studies see heart risk with Glaxo diabetes drug (Studier viser hjerterisiko for Glaxos diabeteslegemiddel)
reuters.com 28.6.2010
(Reuters) - Two studies released on Monday reported serious heart risks with GlaxoSmithKline Plc diabetes pill Avandia as U.S. regulators decide whether the drug should stay on the market. (...)
Dr. Steven Nissen, the lead author and an outspoken Avandia critic, said the results from more than 35,000 patients gave a more complete picture that reinforced his earlier concerns.
"A drug that increases the risk of heart attack by a third or more in diabetics represents a huge public health burden," Nissen, the Cleveland Clinic's head of cardiology, said in an interview. He said the drug should go off the market.
Glaxo shares fell 1.1 percent in London trading and nearly 1 percent on the New York Stock Exchange. (...)
GlaxoSmithKline denies it has settled thousands of lawsuits over rosiglitazone (Avandia) (GlaxoSmithKline benekter å ha forliket tusener av søksmål over rosiglitazone (Avandia))
BMJ 2010;340:c3010 (7 June)
GlaxoSmithKline has denied claims that it has settled "thousands" of the lawsuits brought against the company by people who had heart attacks and strokes while taking the anti-diabetic drug rosiglitazone (Avandia).
A company spokeswoman told the BMJ that many settlements, as reported by Reuters (www.reuters.com/article/idUSLDE65029L20100601), which later issued an update, and by other media outlets, did not happen. (...)
Avandia Side Effects May Have Hurt or Killed 100,000 People: Draft Study (Sideeffekter fra Avandia kan ha skadet og drept 100 000 mennesker)
aboutlawsuits.com 11.6.2010
A draft study by an FDA scientist has linked side effects of Avandia to tens of thousands of heart problems among elderly users, and suggests that more than 100,000 Americans may have suffered heart attacks, strokes or other problems from Avandia since the drug was introduced.
The draft Avandia study (pdf) was performed by drug safety reviewers from FDA and the Centers for Medicare and Medicaid Services (CMS). According to a story by Pharmalot, a drug reviewer at the FDA is pushing for the study to be published in a medical journal in the near future, while the FDA is continuing its own analysis of the safety of GlaxoSmithKline’s diabetes drug. (...)
Glaxo settles hundreds of Avandia suits: lawyer (Glaxo forliker hundrevis av søksmål for Avandia, ifølge advokat))
reuters.com 11.5.2010
(Reuters) - GlaxoSmithKline Plc has settled with nearly 700 people who say they suffered harm because they took the diabetes drug Avandia, a lawyer involved with many of the cases told Reuters on Tuesday. (...)
Glaxo Said to Pay About $60 Million in First Avandia Settlement (Glaxo hevdes å ha utbetalt 60 millioner dollar i første Avandia-forlik)
businessweek.com 10.5.2010
May 10 (Bloomberg) -- GlaxoSmithKline Plc has agreed to pay about $60 million in the first settlements of lawsuits alleging the company’s Avandia diabetes drug causes heart attacks and strokes in some users, people familiar with the accords say. (...)
Regulators approved Avandia for sale in the U.S. in 1999 and the medicine tallied annual revenue of $3 billion by 2006, including sales of a combination of Avandia and another drug. (...)
Rosiglitazone, marketing, and medical science (Rosiglitazone (Avandia), markedsføring og medisinsk forskning)
BMJ 2010;340:c1848 (7 April)
Feature,doi:10.1136/bmj.c1849 Observations,doi:10.1136/bmj.c1819
Forsøk på å tone ned mulig hjerterisiko for et populært diabeteslegemiddel reiser spørsmål om det trenges fundamentale endringer innen legemiddelkontroll, skriver Ray Moynihan (Attempts to play down the potential cardiac risks of a popular diabetes drug raise questions about the need for fundamental changes in drug regulation, writes Ray Moynihan)
Når du fra sidelinjen følger skjebnen til det storselgende diabeteslegemiddel rosiglitazone (Avandia), kan du ikke unngå å tenke på en Hollywood-thriller. Der er en scene hvor en ledende forsker gjør hemmelige opptak fra et møte med firmaets ledelse, en tung kongressgranskning, og en bitter juridisk kamp som venter i kulissene. Men når du ser nøyere på det er virkeligheten mer underlig enn fiksjon. Det er vist at et nytt og dyrt legemiddel, som øker risikoen for hjertesvikt og er mistenkt for å øke risikoen for hjerteanfall hos millioner av mennesker rundt omkring i verden, holdes på markedet av et industrifinansiert kontrollsystem, til tross for signaler fra ledende sikkerhetseksperter som sier av det bør trekkes fra markedet. Selv benekter legemiddelprodusenten linken til hjerteanfall og peker på bevis som støtter sine påstander. Men detaljene i den virkeligheten som brettes ut tyder nå på en velkjent sammensmeltning av medisinsk forskning og markedsføring av legemidler. (...) (Casually following the fortunes of the blockbuster diabetes drug rosiglitazone (Avandia), you can’t help but imagine a Hollywood thriller. There is the scene where a leading scientist secretly records a meeting with drug company executives, a high powered congressional investigation, and a bitter legal battle waiting in the wings. Yet when you look more closely, the facts are even stranger than fiction. An expensive new drug shown to raise the risk of heart failure and suspected of increasing the chance of heart attacks has been taken by millions of people around the world and is being kept on the market by an industry funded regulatory system, despite calls from senior safety experts to withdraw it. For its part, the drug’s manufacturer strongly denies the link with heart attacks and points to evidence to back its claims. But the details of this unfolding real life drama suggest a now familiar merging of medical science and drug marketing.)
American Council on Science and Health
BMJ 2010;340:c1819 (7 April)
The mission of the American Council on Science and Health has remained the same since it was formed over 25 years ago: to promote sound science and help the public distinguish genuine health threats from purely hypothetical ones.1 Unashamed to take an unpopular stance on the big issues of our times, the council regularly weighs in on heated public debates about food safety, drug regulation, and potentially toxic pollution. The main targets of its criticism, however, are generally not the chemical giants, drug companies, or the food industry. Rather these industries are the council’s funders. The council sees the real threat as coming from those who believe chemicals are inherently dangerous, those who want to see tougher drug safety standards, and those obsessed with exposing conflicts of interest within the healthcare establishment. (...)
Rosiglitazone in the UK: down but not out (Rosiglitazone (Avandia) i Storbritannia: faller men ikke helt)
BMJ 2010;340:c1849 (7 April)
Feature doi:10.1136/bmj.c1848 Lobby Watch doi:10.1136/bmj.c1819
Go to the website of the Medicines and Healthcare products Regulatory Agency (MHRA; www.mhra.gov.uk) and you can find a statement released on 3 March 2010 about the drug rosiglitazone (Avandia). It’s essentially a brief summary of the view of the agency, and that of the European Medicines Agency (EMEA), on the safety of this diabetes medicine. Its presence and content, though, are a bit odd. The message is that EMEA completed a thorough review of the safety of the thiazolidinediones—the class from which the drug comes—in 2007, concluding that "the balance of risks and benefits of rosiglitazone remain favourable in its licensed indications." Why does this conclusion need restating two-and-a-half years later? (...)
Positiva artiklar om Avandia kopplas till industrin
lakemedelsvarlden.se 22.3.2010
Enligt en genomgång som publicerats i British Medical Journal har många av de forskare som bedömt att fördelarna överväger nackdelarna med diabetesmedlet Avandia från Glaxosmithkline kopplingar till industrin.
Författarna bakom genomgången menar att detta är ytterligare ett bevis för att det behövs förändringar i systemet för att inte förtroendet för vetenskapliga artiklar ska försvinna helt. Totalt gick forskarna från bland annat Mayo Clinic i Rochester i USA igenom 202 vetenskapliga artiklar som publicerats sedan maj 2007. (...)
LÄNKAR Läs artikeln i BMJ. (...)
Researchers Find Link between Avandia Defenders and Drug Companies (Forskere finner link mellom Avandia-forsvarere og legemiddelfirmaer)
lawyersandsettlements.com 21.3.2010
Rochester, MN: Forskergruppes resultater viser at eksperter som forsvarte Avandia mot negativ publisitet hadde økonomiske forbindelser til legemiddelfirmaet GlaxoSmithKline. Resultatene reiser spørsmål om etikken til studieforfattere med forbindelser til legemiddelindustrien. (...) (Rochester, MN: A team of researchers has found that many of the experts who defended Avandia against negative publicity actually have financial ties to drugmaker GlaxoSmithKline. The findings raise questions over the ethics of study authors who have ties to the pharmaceutical industry.)
The study, published in the British Medical Journal on 3/18/10, concludes, "Disclosure rates for financial conflicts of interest were unexpectedly low, and there was a clear and strong link between the orientation of authors' expressed views on the rosiglitazone controversy and their financial conflicts of interest with pharmaceutical companies." (...)
The study, published in the British Medical Journal on 3/18/10, concludes, "Disclosure rates for financial conflicts of interest were unexpectedly low, and there was a clear and strong link between the orientation of authors' expressed views on the rosiglitazone controversy and their financial conflicts of interest with pharmaceutical companies." (...)
Many Avandia defenders have drug co. ties: study (Mange forsvarere av Avandia hadde forbindelser til legemiddelfirmaer)
reuters.com 18.3.2010
(Reuters) - Praktisk talt alle eksperter som skrev fordelaktig om GlaxoSmithKline Plcs kriseramte diabeteslegemiddel Avandia hadde økonomiske forbindelser til legemiddelfirmaer, et resultat som viser behovet for å reformere slike forbindelser, uttalte amerikanske forskere torsdag. (Virtually all of the experts who wrote favorably about GlaxoSmithKline Plc's troubled diabetes drug Avandia had financial ties to drug makers, a finding that shows the need for reform of such relationships, U.S. researchers said on Thursday.)
A team at the Mayo Clinic in Rochester, Minnesota, pored through more than 200 scientific studies and commentaries that offered positive opinions about the drug after a May 2007 study suggested Avandia significantly increased the risk of heart attacks.
De fant at 94 prosent av forfattere som forsvarte legemidlet, kjent under det generiske navnet rosiglitazone, hadde forbindelser til legemiddelfirmaer, og nesten halvparten hadde økonomiske forbindelser som representerte interessekonflikter. (...) (They found that 94 percent of the authors who defended the drug, known generically as rosiglitazone, had ties to drug companies, and nearly half had financial ties that presented a conflict of interest.)
GSK hid heart risks of diabetes drug, claims Senate committee (GSK skjulte hjerterisiko for diabeteslegemiddel, hevder senatskomité)
BMJ 2010;340:c1107 (23 February)
The US Senate’s Finance Committee has claimed that GlaxoSmithKline (GSK) knew that "there were possible cardiac risks associated with Avandia" (rosiglitazone) for several years before a 2007 study in the New England Journal of Medicine showed a link between the drug and heart attacks.
The committee released a 342 page report on Saturday 20 February. It said the company should have warned patients and the Food and Drug Administration. "Instead," the report says, "GSK executives attempted to intimidate independent physicians, focused on strategies to minimize or misrepresent findings that Avandia may increase cardiovascular risk, and sought ways to downplay findings that a competing drug might reduce cardiovascular risk." It says that another drug, pioglitazone (Actos), might pose less risk to patients. (...)
Senate Report Says GSK Knew of Avandia Heart Attack Risks (Senatrapport viser at GSK visste om risiko for hjerteinfarkt ved bruk av Avandia)
pharmpro.com 22.2.2010
NEW YORK — A Senate report said Saturday that drug maker GlaxoSmithKline knew of possible heart attack risks tied to Avandia, its diabetes medication, years before such evidence became public.
Sen. Max Baucus, chairman of the Senate Finance Committee, and Chuck Grassley, the committee's ranking Republican, released the report, which follows a two-year inquiry. (...)
Avandia (rosiglitazone): Ongoing Review of Cardiovascular Safety
fda.gov 22.2.2010
[Posted 02/22/2010] FDA notified healthcare professional and patients that it is reviewing the primary data from a large, long-term clinical study, RECORD, on possible cardiovascular risks with the diabetes drug, Avandia (rosiglitazone). In addition to the clinical trial, a number of observational studies of the cardiovascular safety of rosiglitazone have been published and FDA has been reviewing these on an ongoing basis. (...)
Glaxo Knew Avandia Caused Heart Risk, Report Says (Update1) (Glaxo visste ifølge rapport at Avandia medførte hjerterisiko)
bloomberg.com 20.2.2010
Feb. 20 (Bloomberg) -- Safety reviewers at the U.S. Food and Drug Administration urged the agency to take GlaxoSmithKline Plc’s diabetes drug Avandia off the market in 2008 because they said it was causing 500 additional heart attacks per month. Two U.S. senators say they want to know why the medicine remains on pharmacy shelves.
A report released today by Senators Max Baucus and Charles Grassley said Glaxo knew Avandia may cause heart damage several years before a study documented the risk and the company pressed doctors to retract warnings about side effects. Baucus, chair of the Senate Finance Committee, and Grassley, the committee’s ranking Republican, are pressing the FDA for answers. (...)
Karen Riley, an FDA spokeswoman, said in an e-mail that the agency is “reviewing the report from the senators, we take it very seriously and we will reply quickly.” (...)
Remove Diabetes Drug Avandia From Market: FDA Documents
news.yahoo.com 20.2.2010
(...) In one of the FDA documents, dated October 2008, Drs. David Graham and Kate Gelperin -- drug safety officials at the agency -- agreed that "rosiglitazone should be removed from the market."
The reports, obtained early by the Times, are yet another chapter in Avandia's checkered history. The drug was once taken by millions worldwide, but that changed after a study released in early May of 2007 by the Cleveland Clinic suggested that Avandia carried cardiovascular risks. That study, which included more than 28,000 people, found that Avandia increased a user's odds of heart attack by 43 percent compared to those not taking the medicine. (...)
In November of the same year, the FDA updated Avandia's labeling to include a caution regarding heart attack risk. At the time, Dr. Janet Woodcock, acting director of the FDA's Center for Drug Evaluation and Research, said that, "we are keeping Avandia on the market because we have concluded there isn't enough evidence to indicate that the risk of heart attack is higher for Avandia than other type 2 diabetes treatments."
The story got more complicated in 2008, as a number of studies emerged tying the use of Avandia to increased bone fracture risk. (...)
Senators Release Report On Avandia
blogs.forbes.com 20.2.2010
The Senate Finance Committee has released a detailed report of its investigations into how the Food and Drug Administration and GlaxoSmithKline handled research into whether the diabetes drug Avandia increases the risk of heart attacks. Neither the FDA nor Glaxo comes out looking very good. A press release, the report, and a letter Senators Charles Grassley and Max Baucus sent to the FDA can all be found here. A New York Times story on differences of opinion detailed in the report is here. Update: And here is Glaxo's response. (...)
Tags: Avandiapanel (...)
Research Ties Diabetes Drug to Heart Woes (Forskning knytter diabeteslegemiddel til hjertelidelser)
NYTIMES.COM 19.2.2010
Hundreds of people taking Avandia, a controversial diabetes medicine, needlessly suffer heart attacks and heart failure each month, according to confidential government reports that recommend the drug be removed from the market. (...)
“Rosiglitazone should be removed from the market,” one report, by Dr. David Graham and Dr. Kate Gelperin of the Food and Drug Administration, concludes. Both authors recommended that Avandia be withdrawn. (...)
GSK says latest Avandia findings are flawed
pharmatimes.com 20.8.2009
GlaxoSmithKline’s diabetes drug Avandia is once again under the spotlight following the release of a study which associates the treatment with a higher risk of heart failure and death among older patients compared with Takeda’s Actos. (...)
As for GSK, spokeswoman Mary Anne Rhyne told Bloomberg that the findings are at odds with three previous studies that showed no difference in heart failure rates between Avandia and Actos. She added that the Canadian study was flawed because it did not properly take into account the different doses of the drugs. (...)
Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study (Uheldige kardiovaskulære hendelser i løpet av behandling med pioglitazone (Actos) og rosiglitazone (Avandia): befolkningsbasert kohortstudie)
BMJ 2009;339:b2942 (18 August)
Objective To compare the risk of acute myocardial infarction, heart failure, and death in patients with type 2 diabetes treated with rosiglitazone and pioglitazone. (...)
Conclusions Among older patients with diabetes, pioglitazone is associated with a significantly lower risk of heart failure and death than is rosiglitazone. Given that rosiglitazone lacks a distinct clinical advantage over pioglitazone, continued use of rosiglitazone may not be justified. (...)
Glaxo's Emails on Avandia Reveal Concern (Glaxos e-poster om Avandia avslører bekymringer)
online.wsj.com 14.1.2009
When a study linking GlaxoSmithKline PLC's diabetes treatment Avandia to increased heart-attack risk was published in 2007, the pharmaceutical giant publicly responded by denouncing the researchers' conclusions. But internal emails indicate some of the company's own scientists were concerned that Glaxo's data were showing the same thing.
"The numbers are the numbers, the analysis is very similar to our own," wrote the company's senior consultant in an email days before the study was published in the New England Journal of Medicine. He added that Glaxo couldn't "undermine" the figures but might find a way to (...)
Doctors Claim Glaxo Dismissed Worries on Avandia (Lege hevder Glaxo avviste bekymringer om Avandia)
wsj.com 19.11.2008
Drug Maker Tried to Make Physician at Maryland Hospital Stop Talking About Concerns; Company Defends Its Effort
HAGERSTOWN, Md. -- Last year, after news broke that the diabetes drug Avandia was linked to a high risk of heart attacks, reports that the drug's maker had tried to stifle safety questions from a prominent Duke University researcher years earlier provoked a furor.
Nå viser det seg at forskeren ved Duke ikke var alene om å antyde mulige hjerteproblemer. En lege ved et lite sykehus linket Avandia til kongestiv hjertesvikt i 2000, men legemiddelprodusenten, GlaxoSmithKline PLC, avviste hennes advarsel og forsøkte å hindre henne å snakke om det med andre leger og sykehus. (...) (Now it turns out that the Duke researcher wasn't alone in suggesting a tie to heart problems. A doctor from a small Maryland hospital linked Avandia to congestive heart failure in 2000, but the drug's maker, GlaxoSmithKline PLC, rejected her warning and tried to make her stop talking about it with other doctors and hospitals, according.)
(Anm: kongestiv hjertesvikt; insufficientia cordis congestiva; stuvingssvikt, svikt i hjartet si pumpeevne som fører til oppstuving av blod i lungene, venene og i levra (som kan blir stor) og andre lekamsdelar; kan føra til ødem (vatersott) både i lungene og i lågtliggjande kroppsdelar – særleg anklane; tilstanden ter seg med tung pust i kvile eller ved små kroppsrøyningar, ortopné (s d), hoste stundom med blodig oppspytt, cyanose m v; TNF, IL-1, IL-6 og andre cytokin innverkar på tilstanden; jf hjartesvikt EN congestive heart failure Kilde: Norsk medisinsk ordbok.)
More objections to Avandia suppressed by Glaxo
fiercehealthcare.com 19.11.2008
We haven't heard anything for a while about Avandia, GlaxoSmithKline's diabetes drug that has been linked to a higher risk of heart attacks, but that doesn't mean no one has been paying attention. Actually, there's been an ongoing investigation in the Senate and House over whether GlaxoSmithKline actively suppressed information about the drug's link to heart attacks, and also whether the FDA ignored what evidence it did have. (...)
Avandia Data Withheld from the FDA
philadelphia.injuryboard.com 6.8.2008
Avandia drug manufacturer, GlaxoSmithKline, failed to disclose several studies about Avandia to the FDA. Earlier this year, the FDA issued a warning letter to GlaxoSmithKline for postmarketing safety reporting failures. This letter can be viewed at http://www.fda.gov/foi/warning_letters?s6714c.pdf. (...)
Avandia: “Starting to Sound A Lot Like Vioxx”
lawyersandsettlements.com 22.12.2008
(...) "It's starting to sound a lot like Vioxx, where statements are made that the risks outweigh the benefits. (...)
FDA review also shows Glaxo diabetes drug risk (FDAs gjennomgåelse viste også risiko for diabeteslegemiddel)
today.reuters.com 25.5.2007
WASHINGTON (Reuters) - En
foreløpig analyse utført av Food and Drug Administration fant en risiko for hjerteanfall for GlaxoSmithKline Plcs diabeteslegemiddel Avandia liknende den som ble rapportert i en studie tidligere denne uke, bekreftet byrået på fredag. (...) (WASHINGTON (Reuters) - A U.S. Food and Drug Administration preliminary analysis found a level of heart-attack risk with GlaxoSmithKline Plc'sdiabetes drug Avandia similar to what was reported in a study earlier this week, the agency confirmed on Friday.)
Forsker innrømmer at han lekket diabetesstudie
NEJM läckte negativ studie till företag
lakemedelsvarlden.se 6.2.2008
Flera veckor innan en mycket negativ studie om diabetesläkemedlet Avandia publicerades fick företaget Glaxosmithkline läsa den. Det gjorde dem väl förberedda på kritiken och personen som läckte studien till företaget är nu i blåsväder.
DIABETES Det är den konkurrerande tidskriften Nature som avslöjat att en medarbetare på New England Journal of Medicine, NEJM, skickade en kritisk studie om Avandia (rosiglitazon) till företaget flera veckor innan publiceringen. Forskaren var en av dem som granskande artikeln för tidskriften, och eftersom allt forskningsmaterial är under strikt embargo fram till dess att det publiceras får han inte sprida resultatet till någon. (...)
Doctor Accused of Leak to Drug Maker (Lege anklaget for lekasje til legemiddelprodusent)
nytimes.com 31.1.2008
A leading member of the Senate said Wednesday that a prominent diabetes expert had leaked an unpublished and confidential medical journal article to GlaxoSmithKline last year, tipping the company to the imminent publication of safety questions involving the company’s diabetes drug Avandia.
The expert, Dr. Steven M. Haffner of the University of Texas Health Science Center in San Antonio, faxed the article to the drug maker after agreeing to read it as part of the peer-review process for The New England Journal of Medicine, according to a statement Wednesday by Senator Charles E. Grassley, Republican of Iowa. (...)
Researcher Admits Leaking Diabetes Study (Forsker innrømmer at han lekket diabetesstudie)
washingtonpost.com 30.1.2008
-- A Texas doctor leaked confidential research to the makers of the popular diabetes drug Avandia weeks before a study was published tying the drug to higher heart risks, the scientific journal Nature reported Wednesday. (...)
Haffner admitted faxing the study to a former colleague now at Glaxo, says the report published online Wednesday in the news section of Nature.
"Why I sent it is a mystery. I don't really understand it. I wasn't feeling well. It was bad judgment," Nature quotes Haffner as saying.
It's not clear that Glaxo took any action after getting the confidential information. Most scientific journals have outside scientists, "peer reviewers," who study research to be sure it is solid before it is published. (...)
Leaked NEJM Manuscript on Rosiglitazone (Avandia) Puts GSK Under Scrutiny
medpagetoday.com 30.1.2008
WASHINGTON, Jan. 30 -- Citing a bad case of poor judgment, an independent reviewer for the New England Journal of Medicine has conceded that he leaked privileged information to GlaxoSmithKline last May on a meta-analysis that cast the company's diabetes drug rosiglitazone (Avandia) in a bad light. (...)
About two months before the rosiglitazone analysis was published, Martin Leon, M.D., an interventional cardiologist at Columbia University, leaked details of the COURAGE trial. (COURAGE Embargo Break: Slip of the Tongue or Sabotage?)
When the Courage data were leaked, Dr. Leon was charged with an embargo break and he was sanctioned by the American College of Cardiology and the NEJM said it would no longer allow him to review manuscripts. Additionally, he would not be permitted to submit editorials, review articles, or commentaries for at least five years. (See: ACC Sanctions Martin Leon, M.D., for COURAGE Embargo Break) (...)
GSK sent Avandia meta-analysis before publication
pharmatimes.com 31.1.2008
GlaxoSmithKline’s Avandia is once again making the headlines after it was revealed that the peer reviewer looking at the now-notorious meta-analysis on the diabetes drug’s safety profile leaked a confidential copy of the article to the firm before it was published in the New England Journal of Medicine. (...)
Dr Nissen has expressed his disappointment over the confidentiality breach, as has Sen Grassley, a fierce critic of the relationship of the pharmaceutical industry with doctors and regulators. He said that “the most troubling aspect of this situation is that the integrity of another aspect of the scientific process is called into question - scientific peer review”. (...)
Hva visste Glaxo?
What Did Glaxo Know? (Hva visste Glaxo?)
forbes.com 21.5.2007
(...) GlaxoSmithKlines egen analyse av diabeteslegemidlet Avandia viste at medisinen deres økte risikoen for hjerteanfall med en tredjedel. (...) (GlaxoSmithKline's own analysis of its diabetes drug Avandia showed that the medicine increased the risk of heart attacks by a third.)
FDA Issues Safety Alert on Diabetes Drug
forbes.com 21.5.2007
(...) Several experts said Avandia was another example of the FDA failing to detect a safety problem early enough.
Glaxo's shares trading in the United States fell $3.85, or 6.6 percent, to $53.89 in afternoon trading.
The report on the diabetes drug's risks follow Glaxo's $2.5 million settlement of a lawsuit filed by former New York Attorney General Eliot Spitzer over the release of data on the safety and effectiveness of its drugs. Spitzer, now New York governor, accused Glaxo of fraudulently withholding some results of studies that had examined the safety of prescribing the antidepressant Paxil to children. (...)
DEMS PLEDGE AVANDIA INVESTIGATION
UPI.COM 21.5.2007
WASHINGTON, May 21 (UPI) -- Two House Democrats have pledged to investigate GlaxoSmithKline and the U.S. Food and Drug Administration over the diabetes drug Avandia.
A Cleveland Clinic study released Monday by the New England Journal of Medicine found that found the drug increases diabetics' chances of heart attack, stroke and death by 40 percent. (...)
Diabetes drug linked to heart attack risk (Diabeteslegemiddel linket til anfallsrisiko)
latimes.com 21.5.2007
A new analysis links the widely prescribed diabetes drug Avandia to greater risk of heart attack and possibly death. (A new analysis links the widely prescribed diabetes drug Avandia to greater risk of heart attack and possibly death.)
More than 6 million people worldwide have taken the GlaxoSmithKline drug since it came on the market eight years ago. Pooled results of dozens of studies revealed a 45 percent greater risk of heart attack, according to the analysis, published online today by the New England Journal of Medicine. (...) (More than 6 million people worldwide have taken the GlaxoSmithKline drug since it came on the market eight years ago. Pooled results of dozens of studies revealed a 45 percent greater risk of heart attack, according to the analysis, published online today by the New England Journal of Medicine.)
Several experts said it was another Vioxx-like example of the government failing to detect a safety problem until millions had taken a drug. Vioxx was a blockbuster arthritis medicine until it was withdrawn in 2004 when heart problems came to light. (...) (Several experts said it was another Vioxx-like example of the government failing to detect a safety problem until millions had taken a drug. Vioxx was a blockbuster arthritis medicine until it was withdrawn in 2004 when heart problems came to light.)
Glaxo's Drug Disaster? (Glaxos legemiddelkatastrofe?)
forbes.com 21.5.2007
The biggest-selling diabetes drug in the world dramatically increases the risk of heart attacks and death from heart problems, according to an analysis by a top cardiologist published online in The New England Journal of Medicine.
Millions of patients have been prescribed the pill, Avandia, since it was introduced eight years ago. Drug maker GlaxoSmithKline (nyse: GSK - news - people) stands to lose much of the $3 billion it makes annually on the pill if the criticisms prove true. Heart attacks are the leading cause of death in patients with diabetes. Rival Actos, from Japanese drug maker Takeda, does not seem to cause heart attacks and may prevent them.
If Avandia does boost heart risk, the repercussions will reach far beyond GlaxoSmithKline or even the patients who may have been harmed by the drug. Right now both houses of Congress are debating bills that would reform the U.S. Food and Drug Administration; these bills must be passed by September or the FDA will have inadequate funds.
A drug safety scandal could reignite the congressional debate, putting Big Pharma back on the defensive. Some of the toughest reforms, like a proposal to create a separate FDA office that would track side effects and yank products from the market, have fallen by the wayside.
Steven Nissen, chairman of cardiology at the Cleveland Clinic, performed the analysis by combing through 42 already completed studies of Avandia. Nissen has become one of the most prominent drug safety advocates in the U.S. since he warned in 2001 that Merck's (nyse: MRK - news - people) painkiller Vioxx caused heart problems. Vioxx was pulled from the market three years later.
Nissen began to worry about Avandia last September when he saw the results of a 5,000-patient clinical trial, called DREAM, that showed Avandia prevented diabetes. Despite this benefit, patients on Avandia were 37% more likely to have heart problems, although the result was not statistically significant.
The DREAM results were "very troubling," Nissen told Forbes.com at the time (see: "Glaxo's Faustian Pill"). In a December letter to The Lancet, the medical journal that published DREAM, he went further, saying the result raised "serious questions about the safety of this agent." Also in December, he became more troubled when another study, meant to show that Avandia worked better than either of two cheaper generic diabetes drugs, also pointed to increased heart problems.
But putting together all of the data proved difficult. With his Vioxx work, Nissen was able to use data that had been presented at an FDA meeting. This time, he had to find studies that had been conducted by Glaxo after Avandia was approved.
Through a Google (nasdaq: GOOG - news - people) search, Nissen found a Web site put up by Glaxo that contained results from all of its clinical trials. The site had been created as a result of a settlement with former New York Attorney General Elliot Spitzer. He found the 42 studies, and he and statistician Kathy Wolski did the analysis and wrote the paper in a matter of days.
In an editorial in the New England Journal, two other veterans of the Vioxx controversy--Bruce Psaty of the University of Washington and Curt Furberg of Wake Forest University--write that there is no clear reason to prescribe Avandia at all now. They call for the FDA to take action and complain that bigger and better studies of the drug should have been completed earlier.
Nissen is doing a study of Actos for Takeda and consults for most major pharmaceutical firms, but he gives all the fees drug makers send him to charity.
Analyses like the one Nissen conducted are fraught with weaknesses; combining data from different studies creates all kinds of statistical problems.
But they have become one of the main ways of raising concerns about risky medical drugs and devices.
Before Vioxx, such combined studies raised concerns about links between common antidepressants and suicidal thoughts. Later, combined data from different studies prevented Pargluva, a medicine from Bristol-Myers Squibb (nyse: BMY - news - people) that was meant to work in a way similar to Avandia, from being approved, also because of heart risks.
More recently, data re-analysis started the debate about the safety of the drug-coated stents made by Johnson & Johnson (nyse: JNJ - news - people) and Boston Scientific (nyse: BSX - news - people), and led the FDA to force Zelnorm, a constipation drug from Novartis (nyse: NVS - news - people), off the market.
One key measure of reform bills in Congress is that they would give the FDA more money to conduct these kinds of analyses. Another, major part of the Senate bill would force companies to make all study results public, making it easier for researchers like Nissen to conduct their own analyses.
Still, James Underberg, a cardiologist at the New York University Medical School, warned that "doctors have to be very careful not to overreact" to this kind of statistical data until statisticians have combed the data.
"It's great that they're identifying a potential problem, but to have it as a lead article in The New England Journal is not sensitive to the consequences" for patients who might stop taking their medicine, says Stuart Weiss, and NYU endocrinologist. Both Weiss and Underberg do speaking or consulting for drug makers; Underberg does not work with Glaxo.
If Avandia is a risky drug, there is perhaps a dark irony to its story. Avandia was invented in the laboratories of Smithkline Beecham, a Glaxo predecessor, two decades ago as one of a class of medicines meant to treat diabetes. But a rival drug, Rezulin, from Pfizer (nyse: PFE - news - people), beat it to market in 1997.
The FDA may have felt pressure to approve Avandia two years later because safety problems were starting to show up with Rezulin. The Pfizer drug was pulled from the market in 2000 because it caused liver problems.
The FDA and Glaxo were unable to comment in time for this story. (...)
Rosiglitazone and Cardiovascular Risk
Published at www.nejm.org May 21, 2007 (10.1056/NEJMe078099)
(...) In this issue of the Journal, Nissen and Wolski1 report the results of a meta-analysis of treatment trials of rosiglitazone, as compared either with other therapies for type 2 diabetes or with placebo. Eligible studies included randomized trials that lasted for at least 24 weeks. The prespecified primary end points of interest were myocardial infarction and death from cardiovascular causes.
(...)
The meta-analysis has a number of strengths. Among these were the effort to include unpublished studies, the prespecified analysis plan, the use of major cardiovascular events as the primary outcome, and an analysis in which rosiglitazone was compared with placebo. In the latter analysis, the odds ratio for myocardial infarction was 1.80 (95% CI, 0.95 to 3.39; P=0.07), and the odds ratio for death from cardiovascular causes was 1.22 (0.64 to 2.34; P=0.55). (...)
Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes
Published at www.nejm.org May 21, 2007 (10.1056/NEJMoa072761)
(...) Conclusions Rosiglitazone was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that had borderline significance. Our study was limited by a lack of access to original source data, which would have enabled time-to-event analysis. Despite these limitations, patients and providers should consider the potential for serious adverse cardiovascular effects of treatment with rosiglitazone for type 2 diabetes. (...)
Diabetes Expert Raised Issue
Of Avandia Heart Risk in 2000
wsj.com 24.5.2007
By ANNA WILDE MATHEWS and JEANNE WHALEN
A leading diabetes expert wrote to the Food and Drug Administration in 2000, raising concerns about a potential heart risk tied to the diabetes drug Avandia.
But, underscoring the debate now playing out over the safety of the GlaxoSmithKline PLC medication, he says he isn't sure if the worries he raised then are valid. (...)
John Buse, a professor at the University of North Carolina who is president-elect of the American Diabetes Association, told the FDA seven years ago that he was concerned about a "worrisome trend in cardiovascular deaths and severe adverse events" in the data submitted to win FDA approval for Avandia. He also warned of "rampant abuse of clinical-trial data" by then-maker SmithKline Beecham, saying the company had "overstated the safety of the drug with respect to cardiovascular issues." (...)
An FDA spokeswoman said the agency at the time "provided a general response thanking him for the letter" and also sent Dr. Buse copies of FDA news releases that explained the agency's actions.
Dr. Nissen said his article pointed out the limits of his analysis, but he added that he "thinks the findings are going to hold up very well in the long run." (...)
Glaxo publiserte ikke risiko for Avandia
Glaxo, Top Ad Spender, Didn't Publicize Avandia Risks(Update4) (Glaxo, toppannonsør, publiserte ikke risiko for Avandia)
By Andrea Gerlin
bloomberg.com 1.6.2007
June 1 (Bloomberg) -- GlaxoSmithKline Plc was the drug industry's top advertiser last year, promoting its asthma and diabetes treatments to patients and doctors.
nformation the company didn't make well known is now drawing more attention.
London-based Glaxo knew its Avandia diabetes pill posed a risk for heart and circulatory complications as early as 1999, when the medicine won U.S. approval. The cardiovascular concern wasn't widely disseminated until May 21 when a Cleveland Clinic Foundation analysis reported that Avandia may cause a 43 percent higher risk of heart attacks than other drugs.
A similar review, begun in 2005 by Glaxo, found that Avandia raised the risk of reduced blood flow to the heart, including heart attacks, by 31 percent. The company gave the review to U.S. regulators and put it on its Web site last year amid more than 2,000 studies. Glaxo says the heart-risk studies, including its own, are flawed and it isn't obligated, or legally required, to highlight every study done on its drugs.
“Why would you publicize it?,'' Glaxo Chief Executive Officer Jean-Pierre Garnier told reporters at the company's annual meeting May 23 in London. "We don't publicize every submission we make to the Food and Drug Administration.''
Glaxo, the world's second-largest drugmaker after New York- based Pfizer Inc., spent $849 million on consumer advertising last year, the most of any pharmaceutical company, according to Nielsen Monitor Plus, a unit of New York-based Nielsen Media Research Inc. (...)
Company sales representatives who knew the risks "denied their existence'' three months later in oral presentations at the American Association of Clinical Endocrinologists' meeting in San Antonio, Texas, FDA officials noted in a July 2001 letter to Glaxo. (...)
Study Cites Safety Questions About Diabetes Drug
Study Cites Safety Questions About Diabetes Drug
nytimes.com 22.5.2007
An article released today by The New England Journal of Medicine raised safety questions about the widely-used diabetes pill Avandia. An analysis of clinical trials concluded that the drug might significantly increase the risk of heart attacks.
Related
GlaxoSmithKline Responds to NEJM Article on Avandia (pdf)
The Food and Drug Administration issued what it called a “safety alert” in response, advising patients who are taking Avandia, particularly those at high risk for a heart attack, to seek advice from their doctors. (...)
The journal’s editor, Dr. Jeffrey M. Drazen, said: “We view this as the best publicly available data on a very important question. It shows what we regard as a preliminary, but worrisome, signal about cardiovascular toxicity of this drug.” (...)
Det viktigste er at pasienter som står på vippen til å begynne med insulin nå får et nytt alternativ, sier Åge Nærdal, administrerende direktør i GSK
Pilleprodusent må betale for feil resepter
aftenposten.no 24.2.2007
For å holde legemiddelindustrien i ørene har Statens legemiddelverk inngått den første refusjonskontrakten. Firmaet må betale gebyr hvis legene ikke følger kriteriene for hvilke pasienter som skal ha medisin på blå resept. (...)
Først ute. GlaxoSmithKline (GSK) er først ut i Norge med å inngå refusjonskontrakt med Statens legemiddelverk. Den gjelder legemiddelet Avandia for diabetes type 2-pasienter. Medisinen skal kun brukes av pasienter der tradisjonelle medisiner ikke virker godt nok, som et alternativ til å begynne med insulinbehandling.
- Vi er fornøyd. Kontrakten er fair. Det viktigste er at pasienter som står på vippen til å begynne med insulin nå får et nytt alternativ, sier Åge Nærdal, administrerende direktør i GSK. (...)
Lege sa at GlaxoSmithKline forsøkte å kneble hans kritikk av Avandia
Diabetes expert accuses drug company of "intimidation" (Diabetesekspert anklager legemiddelfirmaer for "trusler")
BMJ 2007;335:1113 (1 December)
The former chairman of research and development at GlaxoSmithKline, Tadataka Yamada, has been asked by a US Senate committee to explain his role in what it describes as the "intimidation" of John Buse, a professor of medicine at the University of North Carolina.
In 1999 Dr Buse raised questions about the cardiovascular safety of the diabetes drug rosiglitazone, which is marketed as Avandia (BMJ 2007;334:1237 doi: 10.1136/bmj.39244.394456.DB). He was speaking at a symposium organised by the American Diabetes Association. (...)
Expert Says Drug Company Threatened Him (Ekspert sa at legemiddelfirma truet ham)
forbes.com 6.6.2007
The controversy surrounding GlaxoSmithKline's diabetes drug Avandia mounted Wednesday as a medical expert prepared to tell lawmakers executives threatened him with legal action when he first raised questions about the treatment's safety.
Dr. John Buse was contacted by SmithKline Beecham in 1999 after drawing attention to a trend in heart problems among patients using Avandia, according to testimony he was prepared to give a House committee. Buse says the representatives from SmithKline, which combined with GlaxoWellcome in 2000, mentioned that some in the company wanted to hold him accountable for hurting sales of the drug.
Buse, soon to become president of the American Diabetes Association, said he eventually signed a clarifying statement with the company that was used to ease concerns from investors.
One year later, Buse sent a letter to the Food and Drug Administration raising the same concerns. (...)
Avandia Maker Threatened to Sue Critic
forbes.com 6.6.2007
The controversy surrounding GlaxoSmithKline's diabetes drug Avandia grew Wednesday as a medical expert told Congress that executives threatened to sue when he first raised questions in 1999 about the treatment's safety.
That testimony, coupled with a recent medical journal analysis highlighting the heart attack risks associated with Avandia, prompted some Democratic lawmakers to rebuke the Food and Drug Administration for failing to protect consumers, and to call for stricter industry regulation. (...)
Dr. John Buse told lawmakers that after he drew attention in 1999 to heart problems among some patients using Avandia, SmithKline Beecham, which later combined with GlaxoWellcome, warned him that some executives wanted to hold him accountable for a $4 billion drop in the company's stock. (...)
Doctor Says Drug Maker Tried to Quash His Criticism of Avandia (Lege sa at legemiddelprodusent forsøkte å kneble hans kritikk av Avandia)
nytimes.com 2.6.2007
When a Congressional committee holds a hearing next Wednesday, the subject will be the safety of the diabetes drug Avandia and whether federal drug regulators have paid close enough attention to its potential risks.
But for one witness who is scheduled to appear, Dr. John B. Buse, a nationally noted diabetes specialist, the hearing will take a different turn, focusing on whether he was the target of an effort by the drug’s maker, GlaxoSmithKline, to silence his criticism of the drug. (...)
Avandia Maker Tried to Silence Critic, Feds Allege
Avandia Maker Tried to Silence Critic, Feds Allege
lawyersandsettlements.com 19.11.2007
November 19, 2007. By Gordon Gibb RSS digg Del.icio.us Seed Newsvine Facebook Washington, DC: A noted physician who has been warning about the dangerous side effects of Avandia since 1999, and who was the target of alleged intimidation by Avandia manufacturer GlaxoSmithKline (Glaxo) (GSK), was vindicated Thursday by the US Senate Finance Committee.
Operating within its jurisdiction over Medicare and Medicaid, the government committee concluded November 15th that Dr. John Buse, a diabetes expert, suffered at the hands of the multinational drug manufacturer, through its attempts to silence its critic and discredit his findings.
Dr. Buse, Professor of Medicine with the University of North Carolina in Chapel Hill, and volunteer President of Medicine and Science for the American Diabetes Association, first raised concern surrounding Avandia in 1999, not long after the oral diabetes drug first came on the market and rose to become a popular drug therapy for those suffering from Type 2 Diabetes.
Rather than consider the merits of an alternative medical opinion, the Committee found that GlaxoSmithKline, through two of its executives, engaged in a campaign to silence and discredit Dr. Buse in an effort to protect their high-flying drug Avandia.
The Committee Report alleges that GlaxoSmithKline's Chief Executive Officer Dr. Jean-Pierre Garnier, and former head of research Dr. Tachi Yamada were behind the intimidation tactics.
Yamada, currently serving as president of the global health program with the Bill and Melinda Gates Foundation, could not be reached for comment. As for Dr. Garnier, according to a Glaxo spokesperson there would be no comment forthcoming from him.
Dr. Yamada has previously denied any and all wrongdoing, as it relates to Dr. Buse. (...)
"...I can assure you that the manufacturer of Avandia™ has said there is nothing to worry about..."
YOUR PHARMACIST MAY HATE YOU
BLOGSPOT.COM 26.5.2007
The Bullshit Exposure Through Dramatization Players Explain What's Going On With Avandia In A Way Everyone Can Understand. (...)
(...) Ms. McDonalds: It's just that....I saw the article in The New England Journal of Medicine, and....
Doctor: Ms. Mcdonalds, I can assure you that the manufacturer of Avandia™ has said there is nothing to worry about, and if there is anyone known for their integrity and honesty, it is large pharmaceutical companies. I know personally I have never had a sales representative from a drug maker in my office who has ever tried to distort or present data in a misleading way in all my years of practicing medicine. You can trust Big Pharma far more than you can some fly by night medical magazine that isn't allowed outside of New England.
Ms. McDonalds: I see that you are a wise clinician. (...)
- De som trenger medisinene, får i dag en mye dårligere behandling enn de ville fått hvis disse medisinene var på blå resept, sier generalsekretær Bjørnar Allgot i Norges Diabetesforbund
Endelig på blå resept
24.8.2004
Etter en lang kamp kommer legemiddelet Avandia nå på blå resept, for enkelte pasientgrupper. (...)
Pasienter i skvis
vg.no 9.11.2003
Flere tusen diabetespasienter får ikke to nye medisiner på blå resept, til tross for at et enstemmig storting i fjor sa ja til det.
Årsak: Helsemyndighetene greier ikke bli enig med produsentene.
- De som trenger medisinene, får i dag en mye dårligere behandling enn de ville fått hvis disse medisinene var på blå resept, sier generalsekretær Bjørnar Allgot i Norges Diabetesforbund.
- Jeg fatter ikke hvordan Stortinget kan akseptere at Helsedepartementet bruker ett år på å gjennomføre et vedtak, sier han. (...)
Avandia's Real Warning Should Be About FDA And Pharma Symbiosis
Avandia's Real Warning Should Be About FDA And Pharma Symbiosis
opednews.com 4.8.2007
They're just dropping like Chinese imports--prescription drugs that turn out to be deadly after FDA approval.
Not just Vioxx--recently found to cause kidney problems on top of the heart attacks for which it was pulled--but its seven deadly sisters named by the FDA's Dr. David Graham before Congress in 2004: Crestor, Meridia, Serevent, Lotronex, Arava, Accutane and Bextra.
After a post-Vioxx damage control campaign--"FDA has confidence in the safety and efficacy of Crestor" read AstraZeneca ads which the FDA pulled; it wasn't that confident--the cholesterol drug Crestor was found in the heart journal Circulation to be eight times more likely to cause rhabdomyolysis, kidney failure or spillage of protein in the urine than other cholesterol drugs. (...)
(Anm: Autoimmune attack underlying kidney failure. Interstitial nephritis, a common cause of kidney failure, has a complex and largely unknown pathogenesis. In a new published paper in The Journal of the American Society of Nephrology, a team of researchers led from Karolinska Institutet shows how interstitial nephritis can develop from an autoimmune attack on the kidney's collecting duct. (medicalnewstoday.com 24.3.2016).)
- FDA-studie viser Avandia-risiko
FDA finally finds the truth about the Diabetes drug Avandia
americanchronicle.com 26.5.2007
This has become repetitive as a drug on the market consumed by millions has been found to cause sever risks not noted when cleared by the FDA for sales. This again shows the lack luster way that your medicines are studied originally. Despite this new charge of a 43% greater risk of a heart attack the FDA fell short of calling for a warning label change at this time. (...)
At the Center of Rosiglitazone Storm, Steven Nissen, M.D., Focuses on Safety
medpagetoday.com 25.5.2007
CLEVELAND, May 25 -- Here, there, and everywhere this week, it was hard to miss Steven E. Nissen, M.D., the Cleveland Clinic cardiologist who revealed heart risks associated with still another prescription drug.
His latest target was rosiglitazone (Avandia), and earlier he set his sights on muraglitazar (Pargluva), a once promising diabetes drug that Dr. Nissen help derail when it was a hair away from FDA approval, and rofecoxib (Vioxx) the Cox-2 inhibitor that was eventually withdrawn from the market.
As director of cardiovascular medicine at the Cleveland Clinic, which is rated as the top heart center in the U.S. by U.S. News and World Report, Dr. Nissen is no stranger to a camera and a microphone. He, personally, is number 72 on Time magazine's list of the 100 most influential people in our world.
But the dustup created this week by his meta-analysis of published data from 42 randomized controlled trials of rosiglitazone has placed him squarely in the glare of critics who charge that Dr. Nissen is an anti-pharmaceutical crusader.
The analysis found a 43% increase in the relative risk of myocardial infarction among diabetics randomized to rosiglitazone (P=0.03). There was also an increase in the number of cardiovascular deaths in the rosiglitazone group, but that didn't reach statistical significance (P=0.06).
Nothing, Dr. Nissen said, could be farther from the truth. "I'm actually a great believer in the value of drugs," he said. "I've devoted most of my life to studying the biology of cardiovascular drugs in an attempt to find new, effective agents."
But at the same time, he has been a leading critic of the Prescription Drug User Fee Act (PDUFA), that allows the FDA to charge drug companies user fees that the agency then uses to pay for its research into drug safety.
Congress is slated to re-authorize PDUFA this year and Dr. Nissen is one of a number of physician-researchers who have been pressing the Democratic majority to re-work the legislation to allow for tougher post-marketing surveillance of new drugs. (...)
Avandia Reax From Congress, Wall Street
Posted by Ed Silverman
pharmalot.com 21.5.2007
(...) Sen. Chuck Grassley, a Republican and ranking finance commitee member:
“We need to know if this is another Vioxx, where the FDA sat on its hands and endangered lives. The FDA has talked a good game about how it’s beefed up post-market surveillance over the last two years, but a case like this undermines that claim. It’ll take more than administrative reforms to fix the system within the FDA. (...)
Sid Wolfe, Public Citizen:
"The New England Journal of Medicine study...should come as no surprise either to the FDA or to Glaxo. In animal studies done prior to its approval, one of the most constant findings was damage to the heart, and within the first six years of approval there have been 689 cases of heart failure reported to the FDA in patients using the drug. In addition, there have been reports of anemia which, along with heart failure, increases the risk for a heart attack. (...)
FDA Study Said to Show Avandia Risk
forbes.com 25.5.2007
The government's own preliminary evaluation of the diabetes pill Avandia confirms the heart risks reported in a study earlier this week and suggests that as many as 60,000 to 100,000 heart attacks might be linked to its use since it came on the market eight years ago, a leading member of Congress said Thursday.
In a floor statement placed in the Senate record, Sen. Charles Grassley also said that safety watchdogs within the federal Food and Drug Administration "several months ago" recommended a "black box" on the drug's label - the strongest possible warning.
It is the first confirmation that the FDA's own analysis of Avandia shows a similar magnitude of heart attack risks - dangers that were first publicly raised in a medical journal report published earlier this week.
Grassley complained that FDA higher-ups have said they want to wait for results of an ongoing study that will not be available for two more years before making a decision.
"That's a long time from now when you have millions of Americans taking this drug," said the statement by the Iowa Republican. "Those numbers seem like a high enough threshold to me for the FDA to warn the American people of the possibility of a problem." (...)
FDA spokeswoman Julie Zawisza confirmed Thursday the internal analysis that Grassley's statement revealed, but added, "we have conflicting data" from individual studies, and therefore "are continuing to review the results of GSK's ongoing trial to determine the actual risk."
She said she could not discuss "ongoing regulatory matters" like the black box warning that Grassley's statement says was urged months ago by the FDA's Division of Drug Risk Evaluation. (...)
Unsafe At The FDA
forbes.com 31.7.2007
Avandia, GlaxoSmithKline's controversial diabetes drug, looks likely to stay on the market with just a warning. And the biggest loser from the debate over the pill is the U.S. Food and Drug Administration itself, which has now had its internal conflicts and past mistakes put on public display.
Two months ago, The New England Journal of Medicine published an article that charged that the top-selling diabetes drug in the world elevated the risk of heart attacks. (...)
Nonetheless, Avandia is now likely to have a warning that its main competitor won't. Many panelists said regulators should take strong steps to warn patients, especially those taking insulin, that Avandia poses a risk to the heart.
The biggest damage from the proceedings, though, may be to the FDA itself.
During the day-long meeting, the agency displayed its weaknesses on drug safety and the wounds that have been caused by years of controversy, giving the agency's critics more ammunition.
Conflicts within the FDA were writ large. David Graham, a drug safety reviewer who played a key role in the mounting criticisms of Vioxx, told the advisory panel that Avandia should be pulled off the market. His boss, Gerald Dal Pan, head of the FDA's Office of Surveillance and Epidemiology, backed him up. But Robert Meyer, a top official in the office that approves drugs, took a more tempered stance, admitting there were fundamental disagreements at the FDA about what to do with Avandia. (...)
–Dette er overraskende resultater, sier avdelingsoverlege Steinar Madsen i Statens legemiddelverk (SLV)
Øker rosiglitazon faren for hjertesykdom?
legemiddelverket.no 22.5.2007
En ny samleanalyse viser at langtidsbehandling med diabeteslegemidlet rosiglitazon (Avandia) kan øke risikoen for hjerteinfarkt og død av hjertekarsykdom. –Dette er overraskende resultater, sier avdelingsoverlege Steinar Madsen. Bedre blodsukkerkontroll slår i dette tilfellet tilsynelatende ikke ut ved mindre hjertekarsykdom. (...)
(Anm: Når man vet at de data, som Statens legemiddelverk selv sitter på viser at det er en mulig økt risiko for hjerteanfall, er det vanskelig (for ikke å si umulig) å forstå at det nevnte resultatet er spesielt overraskende.
Når SLV bruker American Diabetes Association (ADA) som referanse, er dette litt merkverdig, ettersom nevnte forening er sponset av legemiddelfirmaene, dvs. inhabil.)
"...the heart risks reported in a study earlier this week and suggests that as many as 60,000 to 100,000 heart attacks might be linked to its use since it came on the market eight years ago..."
FDA Study Said to Show Avandia Risk
washingtonpost.com 25.5.2007
The government's own preliminary evaluation of the diabetes pill Avandia confirms the heart risks reported in a study earlier this week and suggests that as many as 60,000 to 100,000 heart attacks might be linked to its use since it came on the market eight years ago, a leading member of Congress said Thursday. (...)
‘I was truly frightened on behalf of our patients’
‘I was truly frightened on behalf of our patients’
timesonline.co.uk 29.5.2007
When he first saw the results of his study two weeks ago, Steven Nissen said that he felt sick and was unable to sleep.
“It was very striking,” he said after the publication of his report on Avandia, the diabetes medicine that is GlaxoSmithKline’s second-bestselling drug. “When you see a signal this strong, I was truly frightened on behalf of our patients.”
The outcome of his “meta-analysis” of 42 clinicial trials was, indeed, troubling. It indicated a 43 per cent increase in the risk of heart attacks and a 64 per cent increase in the risk of death from cardiovascular causes connected to the drug. (...)
"...is a sign that doctors probably were unaware of the drug's possible role in their patients' heart problems"
Diabetes Drug Side Effect Reports Triple
forbes.com 13.7.2007
In the month after a surprising analysis revealed possible heart risks from the blockbuster diabetes drug Avandia, reports of side effects to federal regulators tripled.
The sudden spike is a sign that doctors probably were unaware of the drug's possible role in their patients' heart problems and therefore may not have reported many such cases in the past, several experts said.
It also shows the flaws of the safety tracking system and suggests that a better one might have detected a potential problem before the drug had been on the market for eight years.
Avandia is used to control blood sugar, helping more than 6 million people worldwide manage Type 2 diabetes, the kind that is linked to obesity. These people already are at higher risk for heart attacks, so news that the drug might raise this risk by 43 percent was especially disturbing.
In the 35 days after May 21, when the New England Journal of Medicine published the analysis on the Internet, reports of heart attacks, deaths and hospitalizations leaped. The sharp rise in reports of heart problems appears in data obtained by The Associated Press through a Freedom of Information Act request to the federal Food and Drug Administration. (...)
"...en av 50 pasienter med type 2 diabetes, som inntar disse legemidler, vil utvikle hjertesvikt innen 26 måneder..."
Two Diabetes Drugs Double Heart Failure Risk: Study (Studie: To diabeteslegemidler dobler risiko for hjertesvikt)
forbes.com 27.7.2007
FRIDAY, July 27 (HealthDay News) -- Patients taking either of the diabetes drugs Avandia or Actos face twice the risk of developing heart failure compared to people not on the popular medications, a new study finds.
This means for every 50 patients with type 2 diabetes taking these drugs, one patient will develop heart failure within 26 months, according to the report released Friday and published in the August issue of Diabetes Care. (...)
The government study, by a medical and safety review team at the Food and Drug Administration, found that patients are at much higher risk of heart problems if they take Avandia, compared to patients taking Actos. Avandia is especially hazardous to patients who are already on insulin, the report found, whereas Actos users can take insulin as well without fearing cardiac side effects, the New York Times reported.
That data could help decide whether or not Avandia remains on drug store shelves, experts said. (...)
On Thursday, Mary Anne Rhyne, a spokeswoman for GlaxoSmithKline, which makes Avandia, responded to the new government review by saying the company continued to believe Avandia was safe, the Times reported. (...)
(Anm: Thiazolidinediones and Heart Failure. Diabetes Care 2007;30:2148-2153.)
Advisers: Avandia Should Stay on Market
Advisers: Avandia Should Stay on Market
forbes.com 30.7.2007
WASHINGTON -
The widely used diabetes drug Avandia should remain on the market, government health advisers overwhelmingly recommended Monday, saying evidence of an increased risk of heart attack doesn't merit removal.
The nonbinding recommendation to the Food and Drug Administration came on a 22-1 vote by the panel.
"We're being asked today to take a very draconian action based on studies that have very significant weaknesses and are inadequate for us to make that kind of decision," said Rebecca Killion, a diabetic from Bowie, Md., and the panel's patient representative.
However, in an earlier 20-3 vote, the panelists said that available data show the drug does increase heart risks.
Panelists said the drug's label should include a so-called "black-box" warning, the most severe the FDA can require, to flag that risk. Some suggested the label caution against using the drug together with insulin because doing so may elevate heart risks. That joint use is currently FDA-approved. The experts also asked that the drug be studied further.
The FDA isn't required to follow the advice of its advisory committees but usually does. (...)
Expert: Diabetes Drug Should Be Pulled
Expert: Diabetes Drug Should Be Pulled
forbes.com 30.7.2007
WASHINGTON - The widely used diabetes drug Avandia should be pulled from the market because of heart risks, a federal scientist said Monday.
Those risks, combined with no unique short-term benefits in helping diabetics control blood-sugar levels, fail to justify keeping Avandia on the market, according to a copy of a slide presentation by Food and Drug Administration scientist Dr. David Graham. (...)
FDA Probes Diabetes Drug
forbes.com 30.7.2007
WASHINGTON -
Government health advisers are being asked Monday to consider whether heart risks associated with the widely used diabetes drug Avandia outweigh its benefits in helping some or all patients. (...)
Glaxo, meanwhile, says its own data show no increase in heart risks with Avandia compared with other diabetes drugs. (...)
Diabetes Drug Avandia Should Be Removed From the Market, Public Citizen Tells FDA Advisory Committee
citizen.org 30.7.2007
Popular Drug Associated With Risks to Multiple Organ Systems Has No Benefit Over Older, Safer Type 2 Diabetes Drugs (...)
Diverse artikler
GlaxoSmithKline to Pay $229 Million to Settle U.S. Avandia Suits
online.wsj.com 24.7.2013
GlaxoSmithKline PLC has agreed to pay $229 million to settle lawsuits in which several U.S. states accused the drug maker of deceptively marketing the diabetes treatment Avandia.
The lawsuits generally alleged the U.K. company misrepresented the safety and efficacy of the drug, which has been linked to increased risk for heart attacks and strokes. The company didn't admit to any wrongdoing or liability under state laws in the settlements.
Glaxo is settling the state Avandia matters to avoid the expense and uncertainty of protracted litigation and trial, a company spokeswoman said Wednesday. The cost of the settlements will be covered by existing provisions, she said. (...)
Glaxo Pays $90 Million to Settle States’ Avandia Claims (Glaxo betaler 90 millioner dollar for å forlike Avandia-krav)
businessweek.com 15.11.2012
GlaxoSmithKline Plc (GSK), the U.K.’s biggest drugmaker, agreed to pay $90 million to settle claims by 37 U.S. states and the District of Columbia that the company illegally promoted the Avandia diabetes medicine.
The settlement resolves claims by state attorneys general that Glaxo misled consumers about whether Avandia caused heart attacks and strokes to pump up sales. The company already has paid more than $3 billion to resolve government probes of its marketing of Avandia and other medications, as well as patient lawsuits over the diabetes drug.
“This settlement, which is covered by existing provisions, marks an important step in resolving long-standing legal matters,” Bernadette King, a U.S.-based spokeswoman for the company, said in an e-mailed statement. (...)
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pharmpro.com 1.6.2012
BATON ROUGE, La. (AP) — GlaxoSmithKline has filed suit against Louisiana Attorney General Buddy Caldwell, alleging that private attorneys hired by Caldwell to prosecute the state's lawsuit against the company have a "personal financial interest" in the suit's outcome.
The Advocate reports (http://bit.ly/N3dWEp) GlaxoSmithKline claims the fee agreement Caldwell has with the attorneys violates the state Constitution and the company's constitutional rights. The firm wants a judge to bar Caldwell from prosecuting the state's suit through private attorneys.
State Attorney General's Office spokeswoman Amanda Larkins issued a statement that read, "We have total confidence in the procedures relied upon to institute this important work for the State."
The state sued GSK in February 2011, alleging the firm misrepresented the safety and efficacy of its prescription diabetes drug Avandia. (...)
RD Legal Funding Offers Lawsuit Financing to Plaintiff Attorneys with Avandia Settlements
marketwatch.com 29.3.2012
CRESSKILL, N.J., March 29, 2012 /PRNewswire via COMTEX/ -- Even after published studies described Avandia's dangerous side effects, Type 2 diabetes sufferers, who are at the highest risk of developing fatal heart disease, were prescribed the drug in order to lower their blood sugar levels. Tens of thousands of suits have been settled by GlaxoSmithKline to resolve claims that its drug Avandia increased the risk of heart attack in Type 2 diabetes patients. Plaintiff attorneys with Avandia settlements, who are still waiting to get paid, are encouraged to contact RD Legal Funding, LLC ("RD Legal"), one of the nation's leading providers of lawsuit funding to attorneys. (...)
GlaxoSmithKline Agrees to Settlement in 20,000 Avandia Lawsuits
openpr.com 5.2.2012
(openPR) - Nadrich & Cohen, LLP reports that GlaxoSmithKline has agreed to settle approximately 20,000 Avandia side effects lawsuits.
Los Angeles, CA, February 3, 2012 – UK drug-maker GlaxoSmithKline has agreed to settle 20,000 Avandia side effects lawsuits. According to a Bloomberg report, the company previously agreed to pay at least $700 million to settle more than 15,000 claims on behalf of patients who said that the drug caused heart attacks, strokes and other complications.
Avandia (rosiglitazone) was first approved by the FDA in 1999 to treat Type 2 diabetes in adult patients. The drug hit the market the same year as another popular diabetes drug, Actos (pioglitazone). The maker of Actos, Takeda Pharmaceuticals, is now facing numerous lawsuits from patients who claim the drug caused them to develop bladder cancer. (...)
Avandia Statute of Limitations Motion to Dismiss Denied by MDL Judge
aboutlawsuits.com 20.9.2011
A federal judge has rejected an attempt by GlaxoSmithKline to throw out dozens of Avandia lawsuits, which the drug maker attempted to argue were filed after the statute of limitations expired.
U.S. District Judge Cynthia M. Rufe, who is presiding over the federal Avandia litigation, denied a motion to dismiss 60 lawsuits filed by former Avandia users who claim the diabetes drug caused them to suffer heart problems.
GlaxoSmithKline argued that the Avandia statute of limitations, which dictates the amount of time an injured party has to file their lawsuit, should have started as early as May 2007, when a study was released that linked Avandia to an increased risk of heart attacks and heart failure.
For purposes of deciding the motion, Judge Rufe applied Pennsylvania law, which generally requires a lawsuit for personal injury or wrongful death to be filed within two years from when the plaintiff sustained their injury. However, under the “discovery rule” in Pennsylvania, the statute of limitations for an Avandia lawsuit would not begin running until the plaintiff knew or reasonably should have known that their injury was caused by side effects of the medication. (...)
SC prosecutor suing GlaxoSmithKline over Avandia
pharmpro.com 1.6.2011
British drug maker GlaxoSmithKline PLC improperly marketed the diabetes drug Avandia to South Carolina consumers, hiding the medication's harmful side effects, according to a lawsuit filed by the state's top prosecutor.
A spokeswoman for the company, however, said GlaxoSmithKline supports both its drug and the ways in which it was marketed.
In a lawsuit filed May 17 in Spartanburg County, Attorney General Alan Wilson argued that the drug maker acted negligently when it claimed that Avandia did not put patients' hearts at risks and could actually reduce the potential for heart problems.
"GSK did not just fail to disclose the potential cardiovascular risks Avandia posed, which include heart attacks and sudden cardiac death, it affirmatively represented that Avandia could reduce diabetics' cardiovascular risks," Wilson wrote. "GSK knew or should have known that these representations were not true and likely to deceive."
First approved by the Food and Drug Administration in 1999, Avandia quickly became the top-selling diabetes pill in the world. The drug works by increasing the body's sensitivity to insulin, a key protein needed for digestion that diabetics don't adequately produce. (...)
Louisiana AG sues GlaxoSmithKline over Avandia
forbes.com 17.2.2011 (Associated Press)
BATON ROUGE, La. -- Louisiana Attorney General Buddy Caldwell is suing British drug maker GlaxoSmithKline PLC, claiming the company hid harmful side effects of the diabetes drug Avandia.
The lawsuit, filed in civil district court this week, accuses Glaxo of illegally marketing, pricing and promoting Avandia and violating Louisiana's consumer protection and unfair trade practices laws. (...)
Glaxo Suit on Avandia Heart Attack Death Settled on Trial's Eve (Glaxo-søksmål om dødsfall grunnet hjerteinfarkt utløst av Avandia forliket like før rettssaken skulle starte)
bloomberg.com 31.1.2011
GlaxoSmithKline Plc said it settled on the eve of trial a lawsuit alleging its Avandia diabetes drug caused a North Carolina man to die of a heart attack, avoiding a jury determination over risks associated with the medicine.
The U.K.’s biggest drugmaker resolved the suit by the family of James Burford, an Avandia user who died in 2006. The company declined to provide details of the accord’s terms. The resolution eliminates the risk Glaxo would face a large jury award, said Navid Malik, a drug-industry analyst at Matrix Corporate Capital in London.
Investors worried it “could lead to substantial punitive damages,” Malik said in a Jan. 25 interview. The company has already agreed to pay almost half a billion dollars to resolve claims it hid the drug’s health risks. “GSK needs to successfully settle as many of these cases as possible.” (...)
Diabetesmidler trukket fra markedet
vg.no 25.10.2010
Diabetesmidler som trolig gir økt fare for hjerte- og karsykdom, ble trukket fra det norske markedet mandag.
Diabetesmidlene Avandia, Avandamet og Avaglim ble trukket fra markedet mandag, og legene må nå forskrive alternative medikamenter, skriver Dagens Medisin.
Midlene inneholder rosiglitazon, som trolig øker risikoen for hjerte- og karsykdom. Fordelene med behandlingen oppveier dermed ikke risikoen, ifølge Statens legemiddelverk. (...)
Avandia, Pharma, and the New FDA
blog.pharmexec.com 6.10.2010
The Harvard prof who wrote the book on FDA (literally) deconstructs the decision on Avandia—and its future implications.
GlaxoSmithKline’s diabetes drug Avandia became mired in such controversy regarding its safety in recent years that it was dubbed “another Vioxx”—exactly what the pharmaceutical industry had vowed never to produce. Two weeks ago, FDA’s decided to restrict access to Avandia, earning it “drug of last resort” status. This long-awaited decision was expected, but there were many unexpected aspects to the way the agency made its decision public.
Pharmaceutical Executive asked Daniel Carpenter, a professor of government at Harvard University and the author of a big new book about FDA called Reputation and Power (Princeton University Press) that is getting a lot of attention in the press, for his take on how the Avandia story has played out—and what it may mean for both FDA and pharma in the future. (...)
GSK regulatory update on Avandia following EMA and FDA reviews
pharmanews.eu.com 27.9.2010
GlaxoSmithKline (GSK) confirms that following a review of Avandia® (rosiglitazone maleate) by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), each agency has announced their individual regulatory decisions and the resulting actions. In the European Union*, the EMA has suspended the marketing authorisation for all rosiglitazone-containing medicines (Avandia, Avandamet® and Avaglim®). As a result, physicians in Europe are being advised that affected patients need to be transitioned to alternative treatment options. The EMA has stated that the suspension will remain in place unless convincing data are provided that identify a group of patients in whom the benefits of the medicine outweigh its risks. (...)
Financial Information
Total sales of Avandia products in the first half of 2010 were £321m (-18%); US £164m (-23%); Europe £72m (-17%); Emerging Markets £37m (-5%); RoW £48m (-6%)**. As a result of the regulatory updates in both the US and EU, GSK now expects global sales of Avandia products to be in a range of approximately £100m - £150m in the second half of 2010 and with minimal annual sales thereafter. These estimates are net of customer returns of product previously sold. Associated one-off costs in 2010 comprising stock write-offs, asset write-offs and other related one-off costs are currently expected to be approximately £100m on a pre-tax basis.
To access the full EMA announcement visit www.ema.europa.eu.
To access the full FDA announcement visit www.fda.gov. (...)
The End Of Drug Withdrawals?
blogs.forbes.com 24.9.2010
If the Food and Drug Administration won’t withdraw marketing approval for GlaxoSmithKline’s diabetes pill Avandia, will it ever yank any drug?
Sure, some side effects will make a medicine too dangerous to keep around. But the decade-long age of mass-market drug recalls – in which an average of one medicine a year has been withdrawn from the U.S. market – looks to be ending thanks to new powers the FDA was granted by a 2007 law, the Food and Drug Administration Amendments Act (FDAAA). Big, headline-grabbing drug withdrawals that affect millions of patients, like those of Baycol, Vioxx, and Zelnorm, could become a thing of the past. (...)
BBC Panorama: "A Risk Worth Taking?" Programme. GlaxoSmithKline Right of Reply Statement
pharmatimes.com 7.9.2010
(...) Allegations that GSK attempted to suppress Dr Nissen's findings
In 2007, Dr. Nissen contacted GSK during the development of his meta-analysis to request information. We directed Dr Nissen to the wealth of information contained within our Clinical Study Register. The site includes study protocols and result summaries, including the results of our own meta-analysis of 42 double-blind, controlled clinical trials of Avandia posted in 2006.
Prior to the publication of Dr Nissen's findings, GSK received an unsolicited copy of the manuscript. Upon reviewing the manuscript, GSK disagreed, and continues to disagree with Dr. Nissen that a meta-analysis of this type can definitively determine risk.
Inadequate warnings for patients with congestive heart failure
Congestive heart failure (CHF) is a well characterised side-effect associated with both of the drugs in the thiazolidinedione class, Avandia and Actos, and this is clearly indicated in the approved labelling for these products. The absence of head-to-head clinical data precludes an accurate estimate of the relative difference in the incidence of CHF between these two medicines. (...)
FDA hearings leave doctors, patients in limbo on Avandia
CMAJ 2010; 182 (12) (September 7)
Amidst allegations of concealed data, increased health risks and biased trials, two days of hearings into the safety of a leading type 2 diabetes drug have left doctors and patients in limbo about continuing to prescribe or take the medicine.
A majority of the 33 experts meeting in Washington, DC July 13 and 14 advised the United States Food and Drug Administration either to withdraw rosiglitazone (Avandia) or add sterner warnings and restrict its use. During a complicated series of nine votes, 12 of the 32 committee members who voted (one abstained) recommended taking the controversial drug off the market. Ten others advised allowing its continued sale, but voted for the warnings.
In another vote, 18 of 31 experts found evidence that rosiglitazone raises the risk of heart attack relative to older medicines and to piaglitazone (Actos), its major competitor. (...)
Nya Avandiadata väger lätt
lakemedelsvarlden.se 26.8.2010
En ny studie som visar liknande hjärt-kärlrisker mellan diabetesmedlen rosiglitazon och pioglitazon kommer inte att få så stor betydelse i den europeiska utredningen om preparatets säkerhet. Det säger Tomas Salmonson vid Läkemedelsverket.
riskbedömning Tomas Salmonson, senior expert vid Läkemedelsverket och vice ordförande i det europeiska läkemedelsverket EMA:s vetenskapliga kommitté, CHMP vill inte kalla den nya studien för någon vågskålstippare. Resultaten, som publicerades på onsdagen på tidskriften Cardiovascular Quality and Outcomes webbplats, är en registerstudie genomförd av USA:s största sjukförsäkringsföretag, Wellpoint.
Deras forskare har jämfört närmare 29 000 försäkringstagare i fyra delstater som behandlats med antingen rosiglitazon (Avandia) eller pioglitazon (Actos) i snitt i 14 månader och sedan följt dem ytterligare 19 månader efter avslutad behandling. Resultatet visar att risken att drabbas av hjärtinfarkt, akut hjärtsvikt eller död är, i princip, densamma i båda grupperna – 4,16 procent i rosiglitazongruppen och 4,14 procent i pioglitazongruppen. (...)
FDA Reviewer, Expert Panelists, Not Happy with Avandia Letter
medpagetoday.com 25.8.2010
Within the next few weeks, the FDA will make a much-anticipated decision on the fate of rosiglitazone (Avandia), the diabetes drug that was the subject of a heated two-day FDA advisory panel meeting in July.
But there's been no quiet before the storm (or light rain, depending on what the FDA decides): A reviewer at the agency is peeved at rosiglitazone-maker GlaxoSmithKline for sending a "misleading" letter to investigators conducting the company's ongoing head-to-head trial -- called TIDE -- which is comparing rosglitazone with competitor pioglitazone (Actos). (...)
FDA reviewer David Graham, MD, called the trial "unethical and exploitative," at the hearing, and said the TIDE trial should be shut down.
He told the New York Times that the summary letter GlaxoSmithKline sent to investigators is "biased, misleading and not truthful." (...)
Whistleblower News Roundup 8.16.10
whistleblower.org 16.8.2010
TIME: After Avandia - Does The FDA Have a Drug Problem?
This article investigates how drugmaker GlaxoSmithKline, producer of the diabetes drug Avandia, convinced the FDA to keep the medication on the market for years by hiding and downplaying important evidence linking Avandia to heart problems, and calling the evidence "inconclusive."
The FDA's handling of the Avandia case (which greatly involves GAP client and noted whistleblower Dr. David Graham) highlights large systemic problems with the agency, including its reliance on drug companies for safety testing and reporting, and an approval process that is not tough enough. GAP's 2009 report, The ABCs of Drug Safety -- Accountability, Balance, and Citizen Empowerment, discusses these issues. (...)
Avandia panel member may be investigated for possible conflicts of interest (Panelmedlem kan bli gransket for mulige interessekonflikter)
BMJ 2010;341:c4083 (3 August)
The US Food and Drug Administration has asked its parent department to investigate possible conflicts of interest relating to one of the members of the panel that recently recommended further restrictions on the drug rosiglitazone (marketed as Avandia), manufactured by GlaxoSmithKline (GSK) and used to control type 2 diabetes (BMJ 2010;341:c3862, 16 Jul, doi:10.1136/bmj.c3862).
After an internal review of disclosure forms the FDA asked the Office of the Inspector General of the Department of Health and Human Services to investigate disclosure or non-disclosure of conflicts of interest by the panel member David Capuzzi.
The Wall Street Journal reported that Dr Capuzzi, a Philadelphia endocrinologist, was one of three panel members who voted to keep rosiglitazone on the market with no additional warnings and said that he defended the drug (http://online.wsj.com, 20 Jul, "Panelist who backed Avandia gets fees from Glaxo"). The drug lowers blood sugar concentrations in patients with type 2 diabetes, but there are questions about whether it increases the risk of cardiovascular disease. (...)
(Anm: Uredelighet og fusk (juks/forskningsjuks) i medisinsk forskning. (mintankesmie.no).)
New Data Supports Link Between Diabetes Drugs, Fractures (Nye data støtter link mellom diabeteslegemidler, benbrudd)
drugs.com 29.7.2010
THURSDAY, July 29 -- New research finds that two widely prescribed diabetes drugs may raise the risk of broken bones in postmenopausal women with type 2 diabetes.
There was also a fracture risk seen among men who had been prescribed either Avandia or Actos plus a loop diuretic.
This isn't the first time such an association has been seen, raising doubts as to whether these drugs, which belong to the class of medications known as thiazolidinediones (TZDs), should be the first choice for treating type 2 diabetes. (...)
Avandia's Exception
forbes.com 27.7.2010
Usually the FDA decides whether to approve drugs by comparing them with sugar pills. But that's not what's happening with GlaxoSmithKline's diabetes drug.
The FDA's experience with Avandia is quite a saga. Two years ago a prominent study revealed that Avandia, a drug used to control blood sugar in diabetics, posed a risk of heart attacks. Then it came out that Avandia's producer, GlaxoSmithKline, hid other data about the risk of heart attacks from the FDA. Two weeks ago an advisory committee of the FDA voted to keep Avandia on the market despite its side effects, evoking sharp reactions from consumer groups and academics. And last week it came out that one of the advisory committee members was a paid speaker for GlaxoSmithKline and another was a paid speaker for its competitor Takeda Phamaceuticals. The FDA knew this but did not inform the committee. (...)
FDA puts rosiglitazone post-marketing trial on hold
BMJ 2010;341:c4017 (26 July)
The US Food and Drugs Administration has suspended a post-marketing trial of the thiazolidinedione rosiglitazone while it looks at whether to withdraw the drug or keep it on the market.
The thiazolidinedione intervention with vitamin D evaluation (TIDE) trial was designed to compare the cardiovascular safety of rosiglitazone (marketed as Avandia) and pioglitazone (Actos) in patients with type 2 diabetes. It was set up at the FDA’s request in 2007.
The FDA has placed a "partial clinical hold" on the trial, which means that no new patients can be enrolled until further notice. Patients already enrolled in the trial will be allowed to continue. (...)
Rosiglitazone Revisited
Arch Intern Med. 2010;170(14):1191-1201 (July 26)
An Updated Meta-analysis of Risk for Myocardial Infarction and Cardiovascular Mortality
Context Controversy regarding the effects of rosiglitazone therapy on myocardial infarction (MI) and cardiovascular (CV) mortality persists 3 years after a meta-analysis initially raised concerns about the use of this drug. (...)
Conclusions Eleven years after the introduction of rosiglitazone, the totality of randomized clinical trials continue to demonstrate increased risk for MI although not for CV or all-cause mortality. The current findings suggest an unfavorable benefit to risk ratio for rosiglitazone. (...)
European Medicines Agency update on ongoing benefit-risk review of Avandia, Avandamet and Avaglim
ema.europa.eu 22.7.2010 (press release)
Doctors reminded to follow current restrictions for rosiglitazone-containing anti-diabetes medicines until further notice
The European Medicines Agency is currently reviewing rosiglitazone to determine the impact of new data from recent publications on the risk of cardiovascular problems on the benefit- risk profile of these medicines. Prescribers in the European Union are reminded to strictly follow the current restrictions in the product information. (...)
Endocrinologist Reflects on Rosiglitazone
medpagetoday.com 22.7.2010
WASHINGTON -- As the FDA processes the vote and discussion from last week's advisory committee meeting on rosiglitazone (Avandia), an endocrinologist who has twice voted to keep the diabetes drug on the market dissected what the recent vote meant in a Perspective published in the New England Journal of Medicine.
Based on the last week's vote, the FDA has two choices, said Clifford Rosen, MD, an endocrinologist and senior scientist at the Maine Medical Center Research Institute in Scarborough.
Either it should add stronger warnings to rosiglitazone's label and create a registry for compassionate use of the diabetes drug, or it should remove the drug from the market, he wrote. (...)
FDA Statement on Avandia TIDE Trial
fda.gov 21.7.2010
The U.S. Food and Drug Administration today informed GlaxoSmithKline (GSK), the manufacturer of the diabetes drug Avandia (rosiglitazone), that the postmarketing trial known as TIDE (Thiazolidinedione Intervention With Vitamin D Evaluation) has been placed on partial clinical hold.
Under the partial clinical hold no new patients may be enrolled into the trial until further notice from the FDA. Patients already enrolled in the trial will be allowed to continue to participate. (...)
FDA committee urges tight restrictions on rosiglitazone
BMJ 2010;341:c3862 (16 July)
An advisory committee to the US Food and Drug Administration has recommended further restrictions on the drug rosiglitazone (Avandia), used to control type 2 diabetes. The decision came after two days of intense hearings on 13-14 July, outside Washington, DC. (...)
Steven Nissen, a cardiologist who has been in the forefront of highlighting the risks of rosiglitazone and who testified to the committee, told the BMJ that the committee’s decision "was about as good as we could have hoped for at this time. It is virtually unprecedented to get an advisory committee to vote to withdraw a drug." (...)
Glaxo Rival Paid Fees to Doctor Who Voted Against Avandia (Glaxo-rival betalte honorar til lege som stemte mot Avandia)
online.wsj.com 20.7.2010
A doctor who voted against the diabetes drug Avandia at a Food and Drug Administration advisory panel last week said he earlier served a paid speaker for the maker of a rival drug.
The statement by Abraham Thomas, head of the endocrinology and diabetes division at Henry Ford Hospital in Detroit, follows the disclosure Monday that another doctor on the panel, David Capuzzi of Philadelphia, is a paid speaker for the maker of Avandia, GlaxoSmithKline PLC. Dr. Capuzzi said in an interview that he hasn't given talks to doctors promoting Avandia but spoke on behalf of a different Glaxo drug. (...)
FDA Orders Enrollment Freeze on Rosiglitazone Trial (FDA ber om at innrullering (verving) fryses for rosiglitazone (Avandia)-forsøk)
medpagetoday.com 21.7.2010
WASHINGTON -- The FDA has ordered GlaxoSmithKline, the maker of rosiglitazone (Avandia), to stop enrolling patients in its ongoing head-to-head outcomes trial comparing the drug with pioglitazone (Actos).
The decision comes after a 19-11 vote last week by the agency's expert advisory panel to keep the trial open. The panel voted 20-12 at the same meeting to recommend that rosiglitazone remain on the market despite an increased risk of cardiovascular events.
Patients currently enrolled in the trial, called TIDE, can continue to participate, the FDA said in a statement posted on its website.
The head-to-head trial was begun at FDA request following an advisory committee meeting in 2007 and has been hampered by sluggish enrollment practically since the beginning, possibly because of safety concerns.
In briefing documents released in advance of last week's advisory committee meeting, FDA reviewer David Graham, MD, called the trial "unethical and exploitative," because its main purpose is to look for a safety signal for rosiglitazone.
He also said the informed consent form for the trial obscures the risks of rosiglitazone while focusing too heavily on a more innocuous portion of the study -- a piece designed to detect vitamin D's effect on cancer.
Graham argued that the trial should be shut down.
"Is it ethical to enroll patients in a clinical trial where the goal is to prove harm?" he asked during last week's joint meeting of the Endocrinology and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee.
"Going into a trial as a human, you expect to get something good out of it," Graham said. "It's a bad deal trial. The best they can hope for is to not get a drug that causes a problem." (...)
Revisiting the Rosiglitazone Story — Lessons Learned
Clifford J. Rosen, M.D.
NEJM 2010 (Published July 21)
In July 2007, 24 members of the Endocrinologic and Metabolic Drug Advisory Committee (EMDAC) and the Drug Safety and Risk Management Advisory Committee of the Food and Drug Administration (FDA) held a joint meeting, which I chaired, and concluded that rosiglitazone, an insulin-sensitizing agent used in treating type 2 diabetes mellitus, was associated with an increased risk of myocardial ischemia.1 This conclusion was based on concordant evidence from three independent meta-analyses performed by the drug's sponsor, the FDA, and Nissen and Wolski.1,2 Nevertheless, the committee voted, as did I, to keep rosiglitazone on the market, although we recommended enhancing efforts to inform patients and providers about potential cardiovascular risk. The committee also recommended more studies to refine the risk estimate, including a complete analysis of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial and large observational cohort studies. (...)
Avandia: A scandalous past and an uncertain future (Avandia: En skandaløs fortid og en usikker fremtid)
postscript.communitycatalyst.org 19.7.2010
Last week’s article by New York Times reporter Gardiner Harris exposed Glaxo SmithKline’s (GSK) flagrant disregard for patient safety. For 11 years GSK suppressed internal studies showing that the world’s former best selling diabetes drug, Avandia, posed a much higher risk of heart attack than its main brand-name competitor, Actos.
Last Wednesday, an FDA advisory review panel concluded a two-day hearing by recommending 20 to 12 that Avandia remain on the market with label revisions and other restrictions. This deeply divided panel included 17 votes to add warnings or restrictions on the drug, and 12 votes to remove the drug from the market.
The members voting for Avandia’s removal said the drug “has no unique benefits and therefore the benefits of the drug do not outweigh the risks.” They also pointed out that Avandia’s primary competitor, Actos, is an acceptable alternative to Avandia and therefore there is no therapeutic necessity to keep Avandia on the market.
Even the use of Actos has been called into question. Harvard researchers based at the Independent Drug Information Service (www.RxFacts.org), note that “in mid-2007 the FDA added black-box warnings cautioning that both rosiglitazone (Avandia) and pioglitazone (Actos) increase the risk of congestive heart failure. These safety concerns, along with an increased risk of fracture, have greatly dampened enthusiasm for use of both of these drugs. (...)
FDA committee urges tight restrictions on rosiglitazone
BMJ 2010;341:c3862 (16 July)
An advisory committee to the US Food and Drug Administration has recommended further restrictions on the drug rosiglitazone (Avandia), used to control type 2 diabetes. The decision came after two days of intense hearings on 13-14 July, outside Washington, DC. (...)
US close: Google disappoints, Goldman pays up and BP caps leak
sharecast.com 15.7.2010
(...) Drugs firm GlaxoSmithKline expects to record legal costs for the second quarter of 2010 of £1.57bn. These relate to an investigation by the US Government into the company's former manufacturing site at Cidra, Puerto Rico; product liability and anti-trust litigation relating to Paxil (paroxetine), and product liability cases regarding Avandia (rosiglitazone) and other products. (...)
(Anm: Seroxat (Paxil) (paroxetine; paroksetin) (SSRI) (mintankesmie.no).)
(Anm: ACS Publications- søk paroxetine (Seroxat; Paxil etc.) (pubs.acs.org).)
(Anm: ACS Publications- søk sertraline (Zoloft) (pubs.acs.org).)
Rosiglitazone Hearing Reveals Not-So-Rosy Rifts at FDA
medpagetoday.com 16.7.2010
This week's FDA advisory committee meeting on rosiglitazone (Avandia) drew back the curtain on the agency's internal politics but left its final decision shrouded in uncertainty.
On Wednesday, the panel voted 20-12 in favor of rosiglitazone's continued availability on the market, although 17 of the 20 supporters called for tougher warnings on the drug's label.
The inconclusive voting came as little surprise given the inconclusive and flawed evidence available, noted endocrinologist David Nathan, MD, of Massachusetts General Hospital in Boston.
Although the FDA usually follows its advisory committee recommendations, the lack of unanimity leaves the agency largely free to do what it wants in deciding the fate of rosiglitazone, Nathan said in an interview.
But what that might be remains anyone's guess, as FDA staffers revealed an unprecedented level of infighting over the embattled drug. (...)
Risiko for AMI, apopleksi, hjertesvigt og død ved behandling med rosiglitazon og pioglitazon
irf.dk 15.7.2010 (Institut for Rationel Farmakoterapi (IRF)
(...) Det mener IRF
• Undersøgelsen tyder på større risiko for apopleksi, hjertesvigt og død ved behandling med rosiglitazon frem for pioglitazon, om end der er tale om en ikke-randomiseret, observationel undersøgelse.
• Ødemer og hjertesvigt er kendte bivirkninger ved glitazoner. Hyppigheden af bivirkninger er ikke detaljeret beskrevet i undersøgelsen. IRF har tidligere tilrådet tilbageholdenhed med anvendelsen af begge glitazoner. IRF finder ikke anledning til at ændre denne advarsel. (...)
Diskussion
Der er tale om en ikke-randomiseret, observationel undersøgelse med risiko for uerkendt bias og confounding.
Perifere ødemer og hjerteinsufficiens er kendte og veldokumenterede bivirkninger ved glitazoner.
IRF har tidligere tilrådet tilbageholdenhed med anvendelsen af begge glitazoner ud over i helt specielle tilfælde, indtil bedre effekt- og sikkerhedsdata foreligger (2). Denne undersøgelse har ikke registreret bivirkninger ved rosiglitazon og pioglitazon. (...)
FDA Joint Advisory Committee Allows GSK Avandia To Stay On Market
regulatoryaffairs.pharmaceutical-business-review.com 15.7.2010
FDA's joint advisory committee has voted to allow GlaxoSmithKline's (GSK) Avandia to remain on the market. The recommendations voted by the committee members range from making no changes to the current label, to revising the label with additional warnings and restrictions to withdrawal from the US market. (...)
FDA Reviews Diabetes Drug Risks
pharmpro.com 13.7.2010
WASHINGTON (AP) — Federal health advisers meet Tuesday to discuss the fate of GlaxoSmithKline's diabetes pill Avandia — once a blockbuster drug that has fallen out of favor since showing potential ties to heart attacks.
After two days of debate, the Food and Drug Administration will ask more than 30 expert physicians to vote on a series of options for Avandia, ranging from new warning labels to pulling the drug from the market.
The agency has been down this road before. In 2007 the FDA assembled a similar group of experts to vote on Avandia's safety, after an analysis of dozens of studies suggested it increased the risk of heart attack.
That group voted 22-1 in favor of keeping Avandia on the market, with additional safety warnings.
The FDA's new panel will be larger — 33 voting members — half of the whom appeared at the 2007 meeting. (...)
A.M. Vitals: Avandia, Avandia, Avandia!
online.wsj.com 13.7.7.2010
New Info: A two-day FDA advisory hearing on the safety of Avandia kicks off today, and there’s fresh fodder for those who would like to see the diabetes drug pulled from the market or its use restricted. The WSJ reports that Sen. Charles Grassley sent the agency a letter that included allegations by a former FDA official that GlaxoSmithKline withheld information about the drug’s cardiac risk, as well as other internal company communications about the product’s safety. Meantime, the New York Times cites documents that show the company “had data hinting at Avandia’s extensive heart problems almost as soon as the drug was introduced in 1999, and sought intensively to keep those risks from becoming public.” A company spokeswoman told the NYT the company didn’t report those data because they didn’t add any new information to what was already known. (...)
Avandia on Trial: Glaxo's Defense Part II
blogs.forbes.com 13.7.2010
At the FDA panel over Avandia, which I'm covering via webcast, GlaxoSmithKline has drawn its line in the sand: it is the Record trial, the biggest study of Avandia's heart risk. We know that later on today, and FDA official will present a pretty blistering attack on this study.
Philip Home, the professor of diabetes medicine from Newcastle upon Tyne in the UK who headed this trial, made a pointed defense of his study. A New England Journal of Medicine editorial recently said that Glaxo had too much influence over the independent researchers running Record, including the data safety monitoring board, or DSMB. One of the authors of that paper, Curt Furberg, is on the FDA panel. (...)
Tags: Avandiapanel (...)
Avandia On Trial
blogs.forbes.com 13.7.2010
This morning, consultants to the Food and Drug Administration are beginning a two-day meeting to decide whether GlaxoSmithKline's Avandia, which may cause heart attacks, should stay on the market.
All ready, the meeting, which I am watching via a webcast, is raising the veil on an internal battle within the FDA. Drug safety officials have now said for years that the signs that Avandia causes heart attacks are grave enough to warrant pulling the drug. Officials who handle reviews of drug efficacy say that the data do not provide enough certainty to warrant taking this step. (...)
Tags: Avandiapanel (...)
Glaxo on red alert as FDA scrutinises diabetes drug Avandia (Kipper Williams)
guardian.co.uk 12.7.2010
The FDA is holding a hearing into Glaxo's controversial blockbuster diabetes drug Avandia to decide if is a potential killer (...)
Glaxo has been accused of trying to silence scientists and of endangering the lives of patients since a 2007 study by a cardiologist at Cleveland Clinic suggested Avandia could raise the incidence of heart attacks by 43%. Britain's biggest drugs company has vigorously defended its drug, producing studies suggesting Avandia is safe, but the pill's sales have halved from £1.4bn in 2006 to £771m last year.
"Since 2007 we have seen results from six controlled clinical trials looking at the cardiovascular safety of Avandia and together they show this medicine does not increase the overall risk of heart attack, stroke or death," said Murray Stewart, Glaxo's vice-president for clinical development. (...)
GSK EU regulatory update on Avandia (rosiglitazone)
pharmanews.eu 12.7.2010
GlaxoSmithKline (GSK) confirmed that on behalf of the European Medicines Agency (EMA), the Committee for Medicinal Products for Human Use (CHMP) is to review the benefit/risk profile of Avandia (rosiglitazone). This follows the recent publication of an observational study and a meta-analysis regarding Avandia since the CHMP last reviewed the product in early 2010. All data generated by the Company has previously been submitted to the EMA.
The Committee is expected to review and discuss the data with the company during its scheduled meeting on 19-22 July.
FDA Advisory Committees are also scheduled to convene 13-14 July to review all the latest available data on Avandia. (...)
Advisory Panel Faces Tough Call on Rosiglitazone, Experts Say
medpagetoday.com 12.7.2010
WASHINGTON -- Despite hints that the FDA may be leaning toward pulling rosiglitazone (Avandia) from the market, it's going to be a tough decision for the advisory committee slated to begin meeting on Tuesday, and things could still go either way, leading endocrinologists predict.
"I think the FDA advisory committee is going to struggle with this because none of the data is conclusive," endocrinology expert David Nathan, MD, of Massachusetts General Hospital in Boston said in an interview with MedPage Today.
However, "damning" conclusions reached in the briefing documents "may provide more support to the advisory committee to [recommend pulling] the drug," Nathan suggested.
The FDA posted a 765-page briefing document on Friday, in advance of this week's hearing. In the document, FDA staff reviewers came down hard on rosiglitazone, saying it should be pulled from the market because of serious cardiovascular risks.
The document included an analysis of the controversial RECORD trial, which GlaxoSmithKline has leaned on for proof of the cardiovascular safety of rosiglitazone. FDA staff reviewers, led by Thomas Marciniak, MD, strongly criticized the trial's design, conduct, and results. (...)
Mixed messages from FDA staff over Avandia safety
pharmatimes.com 12.7.2010
Staffers at the US Food and Drug Administration are divided as to what action, if any, should be taken on GlaxoSmithKline’s Avandia ahead of an eagerly-anticipated advisory committee meeting concerning the diabetes drug this week.
The FDA has released documents ahead of a joint meeting of the Endocrinologic and Metabolic Drugs and the Drug Safety and Risk Management advisory committee on July 13-14 to evaluate Avandia (rosiglitazone). The review will focus primarily on the cardiovascular safety of the drug and panelists will look at results from the RECORD study, and different meta-analyses, some comparing Avandia to Takeda’s Actos (pioglitazone). (...)
UPDATE 1-US experts urge limits for some drug safety trials
reuters.com 9.7.2010
(...) In its report, the IOM said randomized controlled trials should only be done when "a responsible policy decision cannot be made based either on the existing evidence or on evidence from new observational studies."
It also said studies of real world use of a drug -- known as observational studies and often done by reviewing insurance claims and other databases -- can yield strong data.
In separate FDA documents released on Friday, FDA staff scientists were split over whether the TIDE trial should continue just as they are divided over whether another major Glaxo trial, RECORD, showed excessive heart-attack risks with Avandia. (...)
EU to investigate safety of GSK’s Avandia
pharmatimes.com 9.7.2010
Regulators in Europe have this morning announced a safety review of GlaxoSmithKline’s controversial diabetes drug Avandia, sending the firm’s shares down.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is investigating the Avandia (rosiglitazone) range of products to determine whether new data on the risk of cardiovascular problems have an impact on their benefit-risk profile. The investigation will cover the drug sold in combination with metformin (Avandamet) and with glimepiride (Avaglim).
In 2008, the CHMP concluded that “on the basis of the available evidence and with the restrictions in place, rosiglitazone retained a small, if diminishing, place in diabetes type 2 therapy”. Now it is looking at new data and will discuss the issue at its next meeting on July 19-22.
The agency adds that “once all relevant data on the benefits and the risks of rosiglitazone have been looked at, the CHMP will issue an opinion on whether or not the marketing authorisations for these medicines should be revoked, suspended or changed”. (...)
A Fix For The Avandia Mess
forbes.com 29.6.2010
If the FDA and GlaxoSmithKline want to extricate themselves from their current public relations predicament surrounding the diabetes drug Avandia, they should put all the data that has been collected about the drug into the public domain.
Avandia effectively lowers blood sugar and is taken by millions of patients. This week, safety concerns were raised again by two prominent studies, followed by calls from members of Congress for the drug to be taken off the market. Meanwhile the company claims that Avandia is safe. (...)
Latest Study on Diabetes Drug Avandia Finds No Heart Risks
businessweek.com 29.6.2010
Report in direct contrast to other new research that found the opposite (...)
"Our observational study does not suggest a significant cardiovascular hazard and may suggest a beneficial effect on ischemic cardiovascular events associated with treatment with rosiglitazone among patients with type 2 diabetes and established coronary artery disease," said Dr. Richard Bach, an associate professor of medicine at Washington University School of Medicine in St. Louis.
Bach presented the findings at a news conference late Monday afternoon, during the American Diabetes Association (ADA) annual meeting in Orlando, Fla.
But on Monday morning, two other major studies came out with findings showing that Avandia increased the risk of cardiovascular trouble when compared to both a placebo and to Actos. Those studies appeared in the Journal of the American Medical Association and the Archives of Internal Medicine. (...)
Although this latest study is much smaller than those presented Monday morning, the findings are not to be dismissed, said Dr. Kirk Garratt, clinical director of interventional cardiovascular research at Lenox Hill Hospital in New York City. (...)
Fra undring til uro
LEDERE Fra Redaktøren
C Haug
Tidsskr Nor Lægeforen 2007; 127:1763 (28.6.2010)
(...) I New England Journal of Medicine ble det 21.5. 2007 publisert en artikkel som viste at rosiglitazon (Avandia) kunne øke risikoen for hjertesykdom hos pasienter med diabetes type 2 (1). Førsteforfatter var Steven Nissen, den samme kardiologen som varslet om mulige bivirkninger av Vioxx i 2001 (2). Tre uker senere avdekket en høring i den amerikanske kongressen at en forsker allerede i 1999 var blitt truet til taushet da han forsøkte å varsle om mulige ugunstige effekter av rosiglitazon på hjertet (3). New England Journal of Medicine publiserte en interimsanalyse av langtidseffektene av rosiglitazon sammen med flere lederartikler allerede i juni 2007 (4, 5). Artiklene beroliger ikke. (...)
Risk of Acute Myocardial Infarction, Stroke, Heart Failure, and Death in Elderly Medicare Patients Treated With Rosiglitazone or Pioglitazone
JAMA. 2010;304(4):(June 28)
Context Studies have suggested that the use of rosiglitazone may be associated with an increased risk of serious cardiovascular events compared with other treatments for type 2 diabetes. (...)
Conclusion Compared with prescription of pioglitazone, prescription of rosiglitazone was associated with an increased risk of stroke, heart failure, and all-cause mortality and an increased risk of the composite of AMI, stroke, heart failure, or all-cause mortality in patients 65 years or older. (...)
Rosiglitazone and the Case for Safety Over Certainty
JAMA. 2010;304(4):(June 28)
Approximately 10 years ago, the thiazolidinediones rosiglitazone and pioglitazone were introduced for the treatment of type 2 diabetes. Like their forerunner troglitazone, which was removed from the market following reports of hepatotoxicity, these drugs act on the gamma subtype of peroxisome proliferator-activated receptors (PPAR-) in the cell nucleus, resulting in heightened insulin sensitivity and improved glycemic control.1 Because insulin resistance is a common feature of type 2 diabetes, the biological effects of thiazolidinediones made these drugs appealing to patients with diabetes and to their physicians who were looking for yet another way to avoid the need for insulin. Within a few years, both drugs became multibillion-dollar products despite no direct evidence that they actually prevented the complications of diabetes. (...)
Glaxo Struggles To Recruit Patients For Avandia Trial (Glaxo sliter med å rekruttere pasienter til Avandia-forsøk)
pharmalot.com 20.5.2010
The big drugmaker is having difficulty recruiting patients for the TIDE trial, which compares the Avandia diabetes pill with Takeda Pharmaceutical’s Actos, but there are ongoing concerns that the study is unethical because it tests a drug with known cardiac risks with what appears to be a safer alternative. And now investigative sites have withdrawn due to poor enrollment, The Wall Street Journal reports. (...)
WSJ: FDA may stop clinical trial on GlaxoSmithKline diabetes drug Avandia (WSJ: FDA kan stoppe klinisk forsøk på GlaxoSmithKlines diabeteslegemiddel Avandia)
news.moneycentral.msn.com 19.4.2010
The U.S. Food and Drug Administration is considering cutting short trials on GlaxoSmithKline’s diabetes treatment Avandia, The Wall Street Journal is reporting.
The drug has been linked to increased risk of heart attack, and some experts have questioned whether it is ethically responsible to test the drug on humans given the potential side effects, The Wall Street Journal reports. The trial was testing the safety of Avandia compared to Takeda’s Actos, another diabetes drug.
Calls to GSK (NYSE: GSK) were not immediately returned Monday morning
If the FDA cuts short the drug trials, it is likely the regulatory agency also would ask GSK to stop selling Avandia, the Journal said in a blog entry Monday. (...)
FDA mulls killing Avandia safety study: report (FDA vurderer å stanse sikkerhetsstudie på Avandia)
reuters.com 18.4.2010
(Reuters) - U.S. regulators are considering ending a safety study on GlaxoSmithKline's diabetes drug Avandia, the Wall Street Journal reported on Sunday, saying the move could also jeopardize the drug's presence in the U.S. market. (...)
UBS weighs Glaxo's Avandia liability
forbes.com 5.3.2010
LONDON -- GlaxoSmithKline PLC could be facing liabilities up to $6 billion over personal injury lawsuits relating to its diabetes drug Avandia, UBS analysts said in a note made public on Friday. (...)
County files lawsuit against drug giant over diabetes medication
tradingmarkets.com 27.2.2010
Feb 27, 2010 (San Jose Mercury News - McClatchy-Tribune Information Services via COMTEX) --
Claiming that a major drugmaker made billions of dollars on a diabetes medication that caused heart attacks and strokes, Santa Clara County on Friday filed a lawsuit charging a decade of false advertising and seeking compensation on behalf of patients and providers in California.
Although patients have filed many personal-injury
lawsuits against Pennsylvania-based GlaxoSmithKline over its drug Avandia, this is the first governmental lawsuit claiming the drugmaker falsely advertised Avandia's benefits and concealed its risks, according to Tamara Lange, Santa Clara County's lead deputy county counsel.
The county alleges that GlaxoSmithKline earned billions of dollars on Avandia and cited an estimate that the drug caused 60,000 to 200,000 heart attacks, strokes and cardiovascular deaths nationwide from 1999 to 2006. (...)
FDA continues review of Avandia, saying nothing until July
pharmatimes.com 23.2.2010
The US Food and Drug Administration says it is not going to be rushed into any action on GlaxoSmithKline’s Avandia amid renewed calls from across the Atlantic that the diabetes drug be withdrawn. (...)
Will GlaxoSmithKline's Blood Money Go Unpunished?
seekingalpha.com 22.2.2010
In the 1970s, economist Milton Friedman penned an opinion piece in The New York Times Magazine that discussed his view on corporations' social responsibilities. Friedman's take on corporate social responsibility was summed up in his famous quote - "There is one and only one social responsibility of business - to use its resources and engage in activities designed to increase its profits so long as it stays within the rules of the game, which is to say, engages in open and free competition without deception or fraud." If the recent years have demonstrated anything, it's that without strong regulations, empowered enforcers, and lawmakers providing legitimate public service as opposed to lining their own pockets and shilling for large companies, corporations will freely and enthusiastically engage in competition utilizing deception and fraud in order to drive profits. (...)
Will GSK Take Avandia Off the Market or Not?
seekingalpha.com 22.2.2010
The Senate report that leaked on Avandia (rosiglitazone) over the weekend has made plenty of headlines. It quotes an internal FDA report that recommends flatly that the drug be removed from the market, since its beneficial effects can be achieved by use of the competing PPAR drug Actos (pioglitazone), which doesn't seem to have the same cardiovascular risks. The two drugs have been compared (retrospectively) head to head, and Avandia definitely seems to have come out as inferior due to safety concerns. (...)
GSK rejects conclusions of Senate Committee on Finance Staff Report on Avandia
worldpharmanews.com 22.2.2010
The Staff Report of the Senate Committee on Finance draws conclusions on the safety of Avandia (rosiglitazone) that are based on analyses that are not consistent with the rigorous scientific evidence supporting the safety of the drug. In addition, the report cherry-picks information from documents, which mischaracterizes GlaxoSmithKline's comprehensive efforts to research Avandia and communicate those findings to regulators, physicians and patients. In fact, the safety and effectiveness of Avandia is well characterized in the label approved by the FDA. (...)
RECORD studiet - rosiglitazons kardiovaskulære risikoprofil
irf.dk 2.9.2009 (Institut for Rationel Farmakoterapi (IRF)
Kort om studiet
• Undersøgelsen er en firma-sponsoreret, ublindet sammenligning af den kardiovaskulære sikkerhed af rosiglitazon + metformin/SU vs. metformin + SU (1).
• Forfatterne konkluderer, at rosiglitazons overordnede kardiovaskulære sikkerhedsprofil ikke er væsentlig dårligere end kontrolbehandlingens.
• Non-inferioritet kan ikke fastslås i forhold til risikoen for letal eller ikke-letal myokardieinfarkt.
Det mener IRF
• Resultaterne er behæftet med nogen usikkerhed på grund af det ublindede design og det lave antal hændelser.
• Rosiglitazon tilbyder ingen klare kliniske fordele, men medfører en øget risiko for hjertesvigt og knoglebrud. Derudover har RECORD ikke formået at afkræfte mistanken om en øget risiko for AMI.
• Glitazonbehandling er forbundet med øget risiko for hjertesvigt, vægtøgning og frakturer. Da der yderligere ikke er dokumenterede positive effekter på primære kardiovaskulære endepunkter, bør glitazoner kun anvendes undtagelsesvist. (...)
Canadian Researchers Question Safety of GSK's Avandia
pharmpro.com 19.8.2009
TORONTO — A group of Ontario researchers is calling into question the continued use of the controversial diabetes drug Avandia, saying a competing drug in the same class is as effective and less dangerous.
The scientists, from Toronto's Institute for Clinical Evaluative Sciences, said people taking Actos or pioglitazone for Type 2 diabetes are 23 per cent less likely to be hospitalized for heart failure and 14 per cent less likely to die than people taking Avandia or rosiglitazone.
"I can't imagine why a patient would want to take rosiglitazone (Avandia) or a doctor would want to prescribe rosiglitazone," principal investigator Dr. David Juurlink said in an interview. (...)
Glaxo’s Avandia Fails to Benefit Alzheimer’s Patients in Study (Glaxos Avandia har ifølge studie ingen nytte for Alheimers pasienter)
bloomberg.com 12.7.2009
July 12 (Bloomberg) -- GlaxoSmithKline Plc’s diabetes drug Avandia failed to benefit patients with Alzheimer’s disease, according to a company-funded study.
The findings are another setback for Avandia, once the biggest-selling drug for diabetes in the world, and raise questions about the theory that Alzheimer’s is a form of diabetes of the brain. Sales of Avandia haven’t recovered since a study linked the drug to heart attacks in May 2007. It generated 805 million pounds ($1.3 billion) last year, down 40 percent from a year earlier.
Analysts and investors hoped Avandia would effectively treat Alzheimer’s disease, and estimated it would generate as much as $300 million annually for the condition. London-based Glaxo halted worldwide development of Avandia for Alzheimer’s disease in April, Bloomberg data shows.
Insulin doesn’t work properly in the brains of patients with Alzheimer’s disease, and previous research suggested Avandia improved mental function in patients without a gene variation linked to the disease. (...)
Glaxo Fails To Learn Lesson of Avandia
forbes.com 6.6.2009
Disclose, disclose, disclose. And definitely don't leave out key facts when you publish your clinical trial.
Today, GlaxoSmithKline is unveiling results of a large clinical trial it says exonerates its Avandia diabetes pill of the charge that it raises the risk of heart attack.
But the scientific paper detailing the results is missing a key fact: 40% of patients analyzed in the study were not taking Avandia at the study's end.
The 4,447-patient study, called RECORD, shows no difference in the rates at which patients were hospitalized for or killed by heart disease whether they were on a drug combination that contained Avandia or not. The study is being published in The Lancet and presented at the annual meeting of the American Diabetes Association in New Orleans.
That would seem to conflict with the headline-grabbing analysis published on May 21, 2007 by Steven Nissen of the Cleveland Clinic, which indicated, based on a pooled analysis of Glaxo's data, that patients who took Avandia were 43% more likely to have heart attacks or strokes. (...)
Some Doctors Question Safety Study on Glaxo's Avandia
online.wsj.com 6.6.2009
A large clinical study designed to test whether GlaxoSmithKline PLC's diabetes drug Avandia can be harmful to the heart appears to have raised more questions than it has answered, with some physicians calling the study flawed.
Safety concerns have dogged Avandia since 2007, when an analysis of the drug suggested that people taking it had a higher chance of suffering a heart attack than people taking other diabetes pills. That analysis helped cut Avandia's sales in half, from £1.65 billion ($2.67 billion) in 2006 to £805 million last year, and it sent researchers scrambling to scrutinize the drug. (...)
Glaxo touts diabetes drug study; critics scoff
philly.com 6.6.2009
The firm said Avandia was found not to raise heart-related hospitalizations. Others cited flaws in the study's design.
GlaxoSmithKline P.L.C.'s diabetes drug Avandia does not increase the risk of heart-related hospitalizations and deaths, according to a company-funded study released yesterday.
Critics said flaws in the study design rendered the results meaningless, and the authors of the paper, published in the British journal Lancet, acknowledged that the data on heart-attack risks were "inconclusive."
Avandia generated $2.2 billion in 2008 sales, but those numbers have been falling since 2007, when Cleveland Clinic cardiologist Steve Nissen published research saying that Avandia increased the risk of heart attacks by about 40 percent. Some of Glaxo's own research has shown increased heart-attack risk. (...)
ADA: Rosiglitazone Increases Risk of Heart Failure, but Not Mortality (ADA: American Diabetes Association Meeting)
medpagetoday.com 5.6.2009
NEW ORLEANS, June 5 -- The final results of the RECORD trial, presented here today, showed no increased overall cardiovascular morbidity or mortality associated with use of the rosiglitazone (Avandia).
There was, however, twice the risk of heart failure and an increased risk of distal fracture in women, Philip D. Home, M.D., Ph.D., of Newcastle University in England and chairman of the RECORD steering committee, said at a press briefing at the American Diabetes Association meeting.
There was not sufficient evidence to draw conclusions about myocardial infarction risk associated with use of the drug, Dr. Home said. (...)
Certain Diabetes Drugs May Pose Eye Risk
healthfinder.gov 7.4.2009
Use of Avandia, Actos tied to a retinal disorder, study finds.
(SOURCE: Elsevier, news release, April 2, 2009)
TUESDAY, April 7 (HealthDay News) -- A class of diabetes drugs called glitazones are associated with an increased risk of a vision-threatening complication called diabetic macular edema (DME), which features swelling and fluid accumulation in the retina.
Glitazones are a newer class of diabetes drugs that includes medicines such as pioglitazone (Actos) and rosiglitazone (Avandia).
The U.S. study of 996 DME patients found that those who took glitazones were 2.6 times more likely to develop DME than those who didn't take the drugs. Even after adjusting for other factors, the risk of DME remained 60 percent higher for patients who took glitazones, said the researchers at the Southern California Permanente Medical Group. (...)
The study, published in the April issue of the American Journal of Ophthalmology, isn't the first to suggest a link between glitazones and DME. But it does confirm that the drugs are "modestly associated" with increased risk of DME, which is a common complication of diabetes. (...)
Study on Avandia
galvestonbay.injuryboard.com 22.2.2009
According to the New England Journal of Medicine, 42 studies in which users of Avandia were compared to people who were not on the medication showed that there was a 43% increase of heart attack in the people who used Avandia. There was also a 64% increased risk of dying from cardiovascular causes while taking the drug. (...)
Chicago sales of diabetes drug remain steady despite report of side effects
news.medill.northwestern.edu 14.1.2009
Iowa Senator Chuck Grassley is preparing a report critical of GlaxoSmithKline PLC and the Food and Drug Administration in connection with Glaxo's top-selling diabetes drug Avandia, which was the subject of a 2007 journal article suggesting that side effects of the drug can lead to heart problems.
The article, in the New England Journal of Medicine, caused Avandia sales to drop, but most Chicago drug stores say sales haven't been affected. (...)
Thiazolidinediones: Do harms outweigh benefits?
CMAJ 2009; 180 (1). (January 6)
(...)
There has been recent debate about the risks and benefits of the use of thiazolidinediones (rosiglitazone and pioglitazone) to treat diabetes. Similar to all other drugs used to treat diabetes, thiazolidinediones were approved by drug regulatory bodies based on their ability to improve glycemic control, rather than based on long-term clinical benefit. However, recent evidence suggests that these drugs may be associated with an increased risk of cardiovascular events and fractures, leading to heightened controversy regarding the appropriate role of thiazolidinediones in the treatment of diabetes. In this issue of CMAJ, Loke and colleagues1 report the findings of a meta-analysis of the impact of thiazolidinediones on risk of fracture and bone loss among patients with diabetes. (...)
Diabetes drugs Avandia and Actos double risk of fractures in women (Diabeteslegemidlene Avandia og Actos dobler risiko for brudd hos kvinner)
pharmatimes.com 10.12.2008
Questions are being asked about GlaxoSmithKline’s and Takeda’s Type 2 diabetes drugs after a study found the medicines were linked to higher bone fracture rates in women.
The study, published in the Canadian Medical Association Journal, found long-term use of Avandia (rosiglitazone) and Actos (pioglitazone) doubled the risk of fractures in women with Type 2 diabetes, without a significant increase in fracture risk in men.
The researchers estimate a fracture would occur in every one in 21 high-risk women – particularly those over the age of 70 – taking either of the drugs for one year. For women with a lower risk, the incidence was still one fracture in every 55 women taking the drugs for more than a year. (...)
GlaxoSmithKline Shareholders File Class Action
avandialawyers.blogspot.com 28.11.2008
It wasn’t just physicians and patients who reacted to the May 2007 report in the New England Journal of Medicine that linked the diabetes drug Avandia to an increased risk of heart attacks. Shareholders of the GlaxoSmithKline, the company that manufacturers Avandia, also had a negative reaction to the news.
The shareholders filed a class action lawsuit in U.S. District Court alleging that GlaxoSmithKline violated securities law by manipulating information that it had on the Avandia drug and by publicly making false and misleading statements about Avandia. Specifically, the shareholders alleged that GlaxoSmithKline did not sufficiently disclose the fact that it had performed a meta-analysis on Avandia that showed an increased risk of heart attacks. (...)
Safety risks higher with Avandia than Actos: study
reuters.com 24.11.2008
CHICAGO (Reuters) - Older diabetics who took GlaxoSmithKline's Avandia to control their blood sugar had a higher risk of death and heart failure while on the drug than those who took Takeda Pharmaceutical's Actos, a drug in the same class, U.S. researchers said on Monday.
They said the head-to-head comparison confirms prior analyses finding Avandia carries greater risks than Actos, particularly in older diabetics.
Surprisingly, the study found no difference in heart attack and stroke risks. But since 75 percent of diabetics die from heart-related causes, the researchers think heart attacks and strokes likely contributed to the overall increased deaths in the Avandia group. (...)
GSK’s Avandia fails in atherosclerotic plaque study
pharmatimes.com 13.11.2008
GlaxoSmithKline’s diabetes drug Avandia (rosiglitazone) has failed to show it can significantly reduce atherosclerosis in patients with type 2 diabetes.
While study results, presented at the American Heart Association scientific meeting, demonstrated the endpoint did not reach statistical significance, the drug giant is maintaining it is “encouraged” by the findings suggesting that treatment with Avandia “may stall the progression of coronary atherosclerosis”.
“This study supports but does not prove the hypothesis that rosiglitazone has greater anti-atherosclerotic effect than glipizide in patients with type 2 diabetes,” said lead study investigator Dr Richard Nesto, Reuters reported.
The study is not good news for GSK, as Avandia has failed to produce positive results in a number of clinical trials and has even been linked to an increased risk of heart attack. (...)
Is Avandia All It's Plaqued Up To Be?
forbes.com 12.11.2008
AHA Conference
Glaxo says a new study provides evidence for the diabetes drug. Two top cardiologists disagree.
GlaxoSmithKline says a new study shows controversial diabetes drug Avandia may clear heart attack-causing plaque out of the arteries.
But an outside researcher called the results "inconclusive" and said Avandia should not be used. Avandia sales have fallen by approximately half since an analysis last May linked it to an increased risk of heart attacks. (...)
Major US consumer group asks FDA to ban drug for diabetes
BMJ 2008;337:a2401 (5 November)
Public Citizen, a US national consumer advocacy group, has petitioned the US Food and Drug Administration to ban the drug rosiglitazone (sold as Avandia), which is prescribed for type 2 diabetes.
The group said that liver failure, often fatal, was a newly documented risk with the drug, which is made by GlaxoSmithKline. Previously the drug had been linked to an increased risk of heart attacks, heart failure, bone fractures, and eye problems, Public Citizen said.
The drug now carries a "black box" warning from the FDA, saying that it may cause heart attacks and congestive heart failure (BMJ 2007;334:1237, doi:10.1136/bmj.39244.394456.DB). (...)
Consumer Group Calls for Ban on Rosiglitazone (Forbrukergruppe ber om forbud mot Rosiglitazone (Avandia))
medpagetoday.com 30.10.2008
WASHINGTON, Oct. 30 -- The consumer advocacy organization Public Citizen has petitioned the FDA to ban the diabetes drug rosiglitazone (Avandia) because of its "life-threatening risks that far outweigh its benefits."
The petition follows just a week after the American Diabetes Association and the European Association for the Study of Diabetes bumped rosiglitazone off a 2006 list of recommended type 2 diabetes treatments. (See: Guidelines Drop Rosiglitazone as Recommended Diabetes Agent)
"The scientific consensus against Avandia is overwhelming," said Sidney Wolfe, M.D., director of Public Citizen's Health Research Group. "The timing of these findings should give the FDA the momentum it needs to act swiftly to prevent further needless deaths and health damage by banning this drug." (...)
Consumer Group Seeks FDA Ban on Avandia
healthfinder.gov 30.10.2008
Public Citizen cites liver failure deaths, other risks of adverse events for diabetes drug.
THURSDAY, Oct. 30 (HealthDay News) -- The diabetes drug Avandia should be banned in the United States because it can cause death from liver failure and poses many other life-threatening risks that greatly outweigh its benefits, the advocacy group Public Citizen said Thursday.
The group said it has identified 14 cases of Avandia-induced liver failure, including 12 deaths. The cases were found in the U.S. Food and Drug Administration's Adverse Event Reporting System. (...)
Avandia Heart Risks Cause Diabetes Associations to Recommend Against Using the Drug (Hjerterisiko medfører at diabetesforeninger fraråder bruk av Avandia)
aboutlawsuits.com 24.10.2008
As a result of serious concerns about the side effects of Avandia, which include an increased risk of heart attacks, congestive heart failure and other serious injuries, the American Diabetes Association and the European Association for the Study of Diabetes have dropped the drug from their consensus statement on type 2 diabetes treatments, unanimously advising against use of the drug.
Statements were published online in Diabetes Care and Diabetologia, updating the groups’ recommendations for treating type 2 diabetes. (...)
ADA: VA Diabetes Trial Appears to Vindicate Rosiglitazone (Avandia) Safety
medpagetoday.com 8.6.2008
SAN FRANCISCO, June 8 -- The last of three major studies of tight glucose control in type 2 diabetes reported at the American Diabetes Association meeting here contained a stunning surprise as a bonus -- an apparent cardiovascular exoneration of rosiglitazone (Avandia).
Like ADVANCE and ACCORD, the other trials, the nearly 1,800-patient Veterans Affairs Diabetes Trial (VADT) found no significant reduction in cardiovascular deaths or events over 7.5 years in patients treated aggressively for glycemic control compared with standard therapy, reported William C. Duckworth, M.D., of the University of Arizona. (...)
But the study's chief statistician, Thomas E. Moritz, M.S., of the Hines VA Hospital in Hines, Ill., dropped a bombshell when he reported that the much-debated drug rosiglitazone (Avandia) did not appear to cause excess cardiovascular events and may have been somewhat protective.
The report was quickly decried as "statistical nonsense" by a prominent cardiovascular specialist, Steven Nissen, M.D., of the Cleveland Clinic.
More than 80% of patients in both arms were taking rosiglitazone. Dr.
uckworth reported that only about 500 patients had cardiovascular events in both groups, with six years of follow-up, well short of the 650 to 700 the investigators expected. (...)
Another Legal Battle for GlaxoSmithKline
avandialegalrights.com 30.4.2008
GlaxoSmithKline faces yet another legal battle, after an Oklahoma man filed a lawsuit claiming Avandia, a popular diabetes medication caused him to experience heart problems that required bypass surgery. The plaintiff alleges in the lawsuit that GlaxoSmithKline should have known that Avandia was linked with a substantial increased danger of (...)
Glitazones as Monotherapy Viewed as No Better than Older Drugs for Type 2 Diabetes
medpagetoday.com 10.4.2008
LONDON. April 10 -- The class of glitazone diabetes drugs offer no benefits as monotherapy compared with older, less expensive drugs, according to the authors of an analysis of data from recent clinical trials. (...)
The FDA has required rosiglitazone packaging to include a black-box warning about a possible increased risk of myocardial infarction. (...)
FDA hits GSK with warning letter over Avandia study data
pharmatimes.com 9.4.2008
GlaxoSmithKline shares have fallen 4% on the news that the firm has been severely criticised by US regulators for inadequate disclosure of data concerning the controversial diabetes drug Avandia.
The US Food And Drug Administration has sent a warning letter to GSK following an inspection at its corporate headquarters in Research Triangle Park, North Carolina. The probe focused on postmarketing reporting requirements relating to Avandia (rosiglitazone) and the company has not complied with FDA regulations.
Specifically, the investigation revealed that between 2001 and 2007, data from 11 clinical studies were omitted from the company's annual reports to the FDA, although the agency acknowledged that the information was disclosed in other ways. Furthermore, the letter stated that nine other studies of the drug were not reported to the agency until September 2007. (...)
FDA: Glaxo Did Not Report Avandia Data (FDA: Glaxo rapporterte ikke Avandia-data)
forbes.com 8.4.2008 (Associated Press)
WASHINGTON -
Federal regulators have issued a warning to GlaxoSmithKline for not reporting safety results on its diabetes pill Avandia, which received a prominent warning label last year.
The Food and Drug Administration said that between 2001 and 2007 the drug maker did not update the agency on more than 10 ongoing studies of Avandia, as required by regulations.
While FDA acknowledges information from the studies was disclosed in other notices to the government, the omissions "are serious and may be symptomatic of underlying post-market reporting failures."
FDA posted the warning letter, dated March 25, to its Web site Tuesday.
Glaxo's shares fell $1.58, or 3.5 percent to $43.45 percent in late morning trading.
Last November, Avandia received a black box warning, the most serious a drug can carry. The labeling alerts doctors and patients that the drug could increase the risk of heart attacks, though the evidence is inconclusive. (...)
Lawsuit Filed Against GlaxoSmithKline by Heart Bypass Patient
lawyersandsettlements.com 16.2.2008
Philadelphia, PA: On February 12, 2008, a lawsuit was filed in the U.S. District Court for the Eastern District of Pennsylvania by Pat and Sandra Kelly of Grove, Oklahoma against GlaxoSmithKline, the maker of the poplar diabetes drug, Avandia. The lawsuit states that GSK was negligent, committed fraud, breached its warranty, failed to warn about the risks associated with the drug, and neglected pharmaco-vigilance. The plaintiffs state that these factors led to the serious injury of Mr. Kelly. (...)
Drugmaker Sued Over Diabetes Pill
money.cnn.com 14.2.2008
NEW YORK (Associated Press) - An Oklahoma man is suing drugmaker GlaxoSmithKline in federal court, claiming its popular diabetes pill gave him heart problems that required bypass surgery.
Attorneys for Grove residents Pat and Sandra Kelly allege in the lawsuit that the drugmaker should have known that Avandia was associated with a significant increased risk of heart failure, heart attack and stroke, among other side effects. (...)
Avandia Drug Company GlaxoSmithKline gets a Helping Hand it Didn’t Deserve
lawyersandsettlements.com 3.2.2008
San Antonio TX: Avandia's manufacturer, GlaxoSmithKline, got an unfair helping hand while many diabetics just got sicker. The diabetes drug Avandia has been linked to heart attacks and other serious physical ailments. But recently, the drug maker got a shot in its own arm when it received advance notice of a peer-review article that was then-to be published in the New England Journal of Medicine. That article was to mention adverse safety concerns surrounding the drug Avandia.
This unfair advantage allowed GlaxoSmithKline to prepare its public strategy to deal with the fall-out from the story well in advance of any negative publicity. That's akin to knowing the score before the game's over. The drug company's sales fell, partly due to the Avandia situation, though the company denies that any senior executive traded stock based on its advance notice of the publication of the study. (...)
Nurse’s Family Files Avandia Wrongful Death Lawsuit against GlaxoSmithKline
lawyersandsettlements.com 18.12.2007
Los Angeles, CA: Rogelio Larosa and his adult son, Eric, of National City, San Diego County, California, filed a lawsuit on Monday, December 17, 2007, against Philadelphia-based GlaxoSmithKline ("GSK"), the maker of Avandia (rosiglitazone maleate), in U.S. District Court, Southern District of California (San Diego) accusing GSK of causing the wrongful death of a Chula Vista nurse due to its negligence, fraud, breach of warranty and a failure to warn about the risks of its drug, Avandia. (...)
Use Of Diabetes Medication By Older Adults Linked With Increased Risk Of Heart Problems, Death
sciencedaily.com 12.12.2007
ScienceDaily (Dec. 12, 2007) — Older patients treated with the diabetes medications known as thiazolidinediones (which include rosiglitazone) had a significantly increased risk of heart attack, congestive heart failure and death, compared with the use of other hypoglycemic drugs, according to a study in the December 12 issue of JAMA. The authors suggest that these results provide further evidence that this class of medication may cause more harm than good. (...)
New Avandia study reaffirms heart risk
usatoday.com 12.12.2007
A new study finds older patients who took Avandia had a higher risk of heart attacks, congestive heart failure and death than those on other diabetes pills. (...)
Canadians Document Excess Mortality with Rosiglitazone (Avandia)
medpagetoday.com 11.12.2007
TORONTO, Dec. 11 -- More than three years of thiazolidinedione monotherapy for diabetes was associated with a 40% increase in relative risk of myocardial infarction and a 29% increase in relative risk of death, researchers here found.
The thiazolidinedione treatment's adverse effects were "primarily with rosiglitazone (Avandia)," Lorraine I. Lipscombe, M.D., M.Sc., of the University of Toronto, and colleagues concluded in the Dec. 12 issue of the Journal of the American Medical Association. There was also a 60% rise in the relative risk of congestive heart failure associated with rosiglitazone. (...)
GSK responds quickly to query Avandia link to osteoporosis
pharmatimes.com 4.12.2007
GlaxoSmithKline has once again jumped to the defence of Avandia, this time in response to a study which claims that treatment with the controversial diabetes drug can lead to an increase in the risk of bone fractures and osteoporosis.
A paper published online in Nature Medicine, involved a study conducted in mice by a team of researchers at the Salk Institute for Biological Studies in La Jolla, California and its senior author Ronald Evans, claimed that long-term Avandia (rosiglitazone) usage in the treatment of type 2 diabetes “may cause osteoporosis due to both increased bone resorption and decreased bone formation”.
However, Prof Evans added that “because Avandia is effective in controlling glucose and restoring the body's sensitivity to insulin, we do not recommend that people stop their treatment. You must balance the benefits against the complications." (...)
Diabetes drug may hike osteoporosis risk
New research finds long-term use of Avandia can lead to brittle bones
msnbc.msn.com 2.12.2007
WASHINGTON - The popular diabetes drug marketed as Avandia may increase bone thinning, a discovery that could help explain why diabetics can have an increased risk of fractures.
New research raises the possibility that long-term treatment with rosiglitazone, as Avandia is also called, could lead to osteoporosis. The diabetes drug is used to improved response to insulin.
While bones seem solid, they constantly are being broken down and rebuilt by the body. Researchers found that in mice, the drug increased the activity of the cells that degrade bones, according to a report in this week’s online issue of Nature Medicine. (...)
Stor belastning å trene i kaldt vær:
- Helsefarlig hardtrening i kulden
vg.no 15.11.2007
Aktiv på ski? Forskere advarer personer som kombinerer mange treningstimer i uka med en krevende jobb på vinteren.
GJELDER IKKE DEN GJENNOMSNITTLIGE MOSJONISTEN: - Det er ingen helserisiko forbundet med trening på moderat intensitet, så lenge man tilpasser forholdene, sier ekspertene. (...)
A Black Box With Shades Of Gray
forbes.com 14.11.2007
After months of controversy, the U.S. Food and Drug Administration and GlaxoSmithKline have added a black box warning--the strongest type--to the product label for Avandia, which until this summer was the top-selling diabetes pill in the world.
Expect even more controversy. (...)
However you slice it, this is a win for GlaxoSmithKline (nyse: GSK - news - people), and it also looks like a political strike-back by the FDA against the outside forces that have been pushing it to be more and more cautious. But it also leaves open space for more battle about this controversial drug. Glaxo will initiate a study comparing Avandia to another drug, but results won't be in until 2014--two years after Avandia goes off-patent.
The decision certainly won't get Congress off the FDA's back. U.S. Sen. Charles Grassley, one of the FDA's biggest critics, said in a statement that the case "was a clear example of the problem within the FDA," because it shows safety reviewers are less powerful than those who put drugs on the market. "The system is off-balance, and that’s not good for public safety.” (...)
Antidiabetikum med økt risiko for karsykdom
Erik Hjelvin
Tidsskr Nor Lægeforen 2007; 127: 2971-2 (15.11.2007)
På bakgrunn av en svært omdiskutert metaanalyse (1) anbefaler Kristian F. Hanssen at «ingen pasienter i Norge bør begynne med glitazoner, og de som bruker slike midler, bør skifte til annen antidiabetisk behandling» (2).
Hanssens konklusjoner går langt utover tilgjengelige data. Å ta medisinene fra velbehandlede pasienter innebærer en risiko og bør ikke gjøres uten god dokumentasjon. (...)
K.F. Hanssen svarer:
Kristian F. Hanssen
Tidsskr Nor Lægeforen 2007; 127: 2972
Det er ikke overraskende at en representant for et legemiddelfirma har en annen oppfatning av et legemiddel enn en som først og fremst skal ivareta pasientens interesse.
Mitt standpunkt er bygd på fem premisser:
- Rosiglitazon er ikke særlig effektivt til å senke HbA1c
Rosiglitazon er vist å kunne utløse hjertesvikt - Rosiglitazon øker bruddforekomsten
- Rosiglitazon har ikke gunstig/ugunstig virkning på hjerte- og karsykdom
- Rosiglitazon er dyrt
Rosiglitazon ville aldri blitt registrert hvis disse forholdene hadde vært kjent på registreringstidspunktet. (...)
Diabetes Drug Gets Heart Risk Warning
forbes.com 14.11.2007
WASHINGTON -
The widely used diabetes drug Avandia got a new warning label Wednesday telling patients that it may, or may not, increase the risk of heart attacks.
Why the confusion? The Food and Drug Administration said studies of the risk are too contradictory to tell if Avandia really is riskier than other medications for Type 2 diabetes.
Still, the FDA put the controversy in a black box on the drug's label - the most severe warning the agency can require - at the behest of its scientific advisers, while it awaits further research to settle the issue. (...)
(Anm: Read the complete MedWatch 2007 Safety Summary including a link to the FDA.
fda.gov (15.11.2007). News Release regarding this issue at:
http://www.fda.gov/medwatch/safety/2007/safety07.htm#Avandia2.)
FDA Puts Black Box On Avandia For Heart Attacks
pharmalot.com 14.11.2007
(...) “FDA has moved expeditiously to review the cardiovascular risks of this drug so that we could inform patients and doctors at the earliest possible time of our findings,” says Janet Woodcock, FDA’s deputy commishr for scientific and medical programs, chief medical officer, and acting director of the Center for Drug Evaluation and Research, in a statement. The “FDA remains committed to making sure that doctors and patients have the latest information about the risks and benefits of medicines.” (...)
Medisin kan gi infarkt
aftenposten.no 12.11.2007
Et hovedpoeng med diabetesmedisiner er å redusere risikoen for hjerteinfarkt. 5000 nordmenn får en pille som nå ser ut til å øke risikoen. (...)
I Norge begynte Staten å betale for medisinen over blå resept i 2004 og legemiddelgiganten GSK startet pågående markedsføring. Mang en norsk lege bruker i dag PC-sekk med Avandia-logo. Salget skjøt i været. (...)
Svak virkning.
- Det er ennå ikke sikkert at Avandia øker risikoen for hjerteinfarkt. At det er usikkert om den kan gjøre det, gjør at den bør tas av markedet.
- De som får medisinen i dag, bør få en annen medisin. Ikke alle er enige med meg i dag, men det tror jeg de er om et år, sier professor Kristian F. Hanssen ved Endokrinologisk klinikk, Aker universitetssykehus.
Han legger til at Avandia heller ikke gir spesielt god demping av blodsukkeret, at det fra før er kjent at den kan bidra til benbrudd hos kvinner og hjertesvikt. (...)
- Gambler ikke leger med folks helse når de fortsatt skriver ut medisinen?
- Ikke hv is den gis til de riktige pasientene og disse følges nøye opp. Altfor høyt blodsukker gir i seg selv dårlig livskvalitet. Hvis andre medisiner ikke virker tilfredsstillende, kan det være nødvendig å bruke medisiner som ikke har gunstig virkning på hjertesykdom. Medisinen balanserer på en knivsegg når det gjelder forholdet mellom nytte og risiko. Det bør ikke komme mange flere negative opplysninger om den, sier Madsen.
Professor Kristian F. Hanssen mener på sin side insulin vil kunne hjelpe mange av dem som bruker Avandia. Hvorfor tør fabrikanten da fortsette salget når risikoen for plutselig død ser ut til å øke?
- Avandia har vært vurdert av europeiske myndigheter nylig. Konklusjonen deres er at nytten er større enn risikoen, sier adm.dir. i GSK Norge, Åge Nærdal.
Fjernet kritiker.
Temperaturen i Avandia-saken økte da en ansatt i det amerikanske legemiddelverket FDA fortalte avisen New York Times at hun ble fjernet fra jobben som sikkerhetskontrollør da hun ba om en advarsel på medisinen.
Avisen beskylder FDA for å ha et for kosete forhold til legemiddelindustrien. Kritikere hevder GSK og andre firmaer lager studier så kortvarige at bivirkninger ikke kan komme til overflaten før de avsluttes. Avandia-saken kan internasjonalt gi skjerpede krav til dokumentasjon før piller når pasient.
- Generelt lager industrien studier som fremhever gunstige virkninger. Studiene er ikke gode nok til å undersøke om medisinene faktisk beskytter mot alvorlig sykdom og død før de slippes på markedet. Det er på høy tid med nye regler for legemiddelstudier og godkjenning av medisiner, sier professor Hanssen. (...)
Lawmaker Probes FDA Decision on Avandia
forbes.com 30.10.2007
Associated Press By MATTHEW PERRONE 10.29.07, 2:31 PM ET
WASHINGTON - A U.S. Senator on Monday asked the Food and Drug Administration to confirm whether its drug safety experts came within one vote of recommending a withdrawal of GlaxoSmithKline's diabetes drug Avandia for safety reasons.
Sen. Charles Grassley of Iowa said his staff learned that an internal panel of government safety experts voted 8-7 to keep the blockbuster pill Avandia on the market earlier this month. In a letter to FDA, Grassley questioned why the agency did not disclose the vote, which reportedly occured at a closed-door meeting Oct. 2.
The Senator did not identify the source of the information. (...)
FDA wants big warning on Glaxo diabetes drug report
reuters.com 24.10.2007
NEW YORK (Reuters) - Food and Drug Administration officials are pushing for a "black box" warning on GlaxoSmithKline Plc's hard-hit diabetes drug Avandia, the Wall Street Journal reported, citing sources.
The warning would be a further blow to the top-selling diabetes drug, which came under pressure last May when a U.S. analysis linked Avandia to a 43 percent higher risk of heart attack in patients. (...)
Nyttan av behandling med Avandia och Actos överväger riskerna
lakemedelsverket.se 22.10.2007
Nyttan med Avandia och Actos vid behandling av typ 2 diabetes, tidigare kallade åldersdiabetes, överväger riskerna. Det fastslår den europeiska läkemedelsnämnden CHMP efter en omfattande utredning. (...)
Bakgrunden till utredningen är information som tydde på en ökad risk för biverkningar vid behandling med dessa läkemedel. Den europeiska utredningen konstaterar att behandling med Avandia kan innebära en ökad risk för kärlkramp och hjärtinfarkt. (...)
Avandia och Actos ska endast användas när annat diabetesläkemedel i tablettform prövats utan önskat resultat. (...)
EMEA says benefit outweighs risk for Avandia and Actos
pharmatimes.com 19.10.2007
European regulators say that the benefits of taking GlaxoSmithKline’s Avandia and Takeda’s Actos outweigh the risks for diabetes suffers but have recommended a label change for the former’s drug.
The European Medicines Agency’s Committee for Medicinal Products for Human Use has completed a review looking at the two thiazolidinediones as part of its “continuous monitoring of the safety of medicines” but that process took on added significance in May when the drug class, but most specifically Avandia (rosiglitazone), was linked to the increased risk of ischaemic heart disease by a meta-analysis published in the New England Journal of Medicine. Information on the risk of bone fractures in women was also looked at. (...)
Alastair Benbow, vice president and European medical director of GSK said that the review shows that the EMEA “recognises the positive benefit risk of rosiglitazone in Europe and its importance in the treatment of patients with type 2 diabetes”. He added that the firm “is confident in the safety profile of rosiglitazone when used appropriately by physicians”, noting that GSK will continue to work with the agency on appropriate wording for the label. (...)
Glitazoner – igjen
Johan Halse
Tidsskr Nor Lægeforen 2007; 127: 2707 (18.10.2007)
Debatten omkring glitazoner i behandlingen av diabetes, spesielt rosiglitazons negative kardiovaskulære profil, går for fullt i medisinske tidsskrifter anført av The New England Journal of Medicine. (...)
Ensuring drug safety: lessons from the thiazolidinediones
The Lancet 2007; 370:1101
(...) These commentators highlight issues that must be taken into account in the ongoing debate about thiazolidinediones. Future trials ought to be designed with these issues firmly in mind. Further, it is no secret that the regulatory system is also in urgent need of repair. Manufacturers must do—in a timely fashion—postmarketing studies that assess the long-term safety of their drugs, and regulatory agencies must hold manufacturers' feet to the fire to ensure that these are performed, performed properly, thoroughly evaluated, and made available to guide decisions about prescribing. Agencies like the US FDA must have the resources and authority to close what is now a potentially dangerous gap. Unless limitations on the understanding, analysis, and communication of drug safety issues are addressed, the thiazolidinediones might simply become the latest in a series of preventable drug disasters. (...)
Actos, Avandia heart failure risks confirmed: study
today.reuters.com 28.9.2007
(...) The latest study in the journal Lancet found heart failure risks are greatest for patients with a history of heart disease and heart failure, but less for those who had no heart problems. Overall the relative risk was 72 percent higher. (...)
Meta -analysis confirms rosiglitazone's poor safety record
BMJ 2007;335:586 (22 September)
Shortcuts from other journals (...)
Rosiglitazone is still approved by the US Food and Drugs Administration (FDA) for the treatment of type 2 diabetes, despite evidence from meta-analyses that it is associated with an increased risk of heart attack and heart failure (...)
More Studies Cast Doubt on Safety of Diabetes Drug
nytimes.com 12.9.2007
Two more studies published in yet another prominent medical journal have raised questions about the safety of Avandia, a once-popular diabetes medicine.
One study found that Avandia, made by GlaxoSmithKline, doubled the risks of heart failure and raised the risks of heart attack by 42 percent. A second study found that Actos, a similar drug made by Takeda, actually lowered the risks of heart attacks, strokes and death but, like Avandia, also raised risks of heart failure.
Taken together, some of the authors said, the two studies in The Journal of the American Medical Association confirm what doctors and patients using Avandia have already done in great numbers, that is, switch to another drug. Sales of Avandia have plunged. (...)
GSK’s Avandia should be pulled from market in light of recent studies, some physicians/experts say
ft.com 19.9.2007
GSK’s Avandia should be pulled from the market in light of recent studies, a number of physicians and industry experts have argued. However, others believe that there is not yet sufficient data to warrant such a conclusion. (...)
Glitazoner og hjertesvigt
irf.dk 31.8.2007
Kort om analysen (...)
Det mener IRF (...)
• At glitazonbehandling øger risikoen for hjertesvigt er veldokumenteret.
• Sammenhængen gælder tilsyneladende både harmløse ødemer og alvorlig, indlæggelseskrævende hjertesvigt.
• Der er data, der taler for, at glitazonbehandling foruden hjertesvigt også kan være associeret med andre alvorlige risici. Det gælder frakturer hos kvinder (2), makulaødem (3) og cancer (4). FDA har konkluderet, at behandling med rosiglitazon er associeret med en øget risiko for myokardieinfarkt (5).
• Alt taget i betragtning vil IRF tilråde en vis tilbageholdenhed med anvendelsen af glitazoner ud over specielle tilfælde, indtil bedre effekt- og sikkerhedsdata foreligger. (...)
The Rosiglitazone Story — Lessons from an FDA Advisory Committee Meeting
NEJM 2007;357:844-846 (August 30)
On July 30, 2007, the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee of the Food and Drug Administration (FDA) convened to discuss the myocardial ischemic risk associated with rosiglitazone treatment in patients with type 2 diabetes mellitus. The joint committee, which I chaired, consisted of 24 experts in cardiovascular disease, epidemiology, biostatistics, and endocrinology. After lengthy discussions, we concluded that the use of rosiglitazone for the treatment of type 2 diabetes was associated with a greater risk of myocardial ischemic events than placebo, metformin, or sulfonylureas. (...)
Glaxo Gets Off With A Warning
forbes.com 7.8.2007
(...) But the panel of scientists were also in broad agreement that the drug does cause an increase in the risk of heart attacks, with some of them recommending that the FDA take some of the strongest steps in its power to limit use of the drug. The FDA is not compelled to follow the advice of its committees, but it usually does. (...)
Unsafe At The FDA
forbes.com 7.8.2007
(...) Monday night, a panel convened by the FDA to weigh the data on the controversial diabetes pill agreed by a 20-3 vote that Avandia does increase the risk of heart attacks, particularly for certain high-risk patients like those who are sick enough to need insulin. But by a 22-1 vote the panel said Avandia should stay on the market, albeit with much stronger warnings. The FDA isn't obligated to follow the advice of its panels, but it usually does. (...)
Survey Report: Future May Be Bleak for Rosiglitizone (Avandia)
medpagetoday.com 6.8.2007
LITTLE FALLS, N.J., Aug. 6 -- Only 9% of the respondents to a MedPage Today poll say they'll continue prescribing rosiglitizone (Avandia) without reservation. One in four think it should be taken off the market. (...)
FDA committees say keep rosiglitazone available but increase warnings
BMJ 2007;335:223 (4 August)
Two Food and Drug Administration advisory committees recommended this week that the FDA should keep rosiglitazone (Avandia), which is used to treat type 2 diabetes, on the market, despite concerns about the raised risk of heart attack in some patients. (...)
David Graham, associate director of the FDA's office of surveillance and epidemiology, told the committee that rosiglitazone should be pulled from the market because, he said, it had caused between 40 000 and 205 000 heart attacks and strokes since 1999. (...)
Glaxo Gets Grilled
forbes.com 30.7.2007
This morning, GlaxoSmithKline defended its controversial diabetes drug, Avandia, in front of a panel of federal advisers convened to decide whether the pill causes heart attacks. (...)
FDA Advisers Vote to Keep Rosiglitazone (Avandia) But Cite Risks
medpagetoday.com 30.7.2007
(...) Members of two FDA advisory panels, meeting jointly, voted 22 to one in favor of continued marketing. Arthur Levin, M.P.H., of the Center for Medical Consumers in New York cast the lone dissenting vote, citing public health issues.
Meanwhile, GlaxoSmithKline, said it applauded the FDA advisers' recommendation as "a positive for patients," according to press release.
Although advisors voted overwhelmingly to recommend that the FDA keep the drug on the market, they also made it clear that they want to see a much narrower market for rosiglitazone. (...)
In an unusual move for agency officials, who normally are reluctant to make on-the-record comments about drugs under review, both Gerald Dal Pan, M.D., M.P.H., director of the FDA's Office of Surveillance and Epidemiology, and David Graham, M.D., M.P.H. associate director of that office, said during the meeting they thought rosiglitazone should be taken off the market.
Dr. Graham said the "point estimates of the relative risk of cardiovascular deaths and non-fatal MIs range from 1.20 to 1.40 to 1.70 for rosiglitazone." (...)
GSK in $1.5b deal with Targacept ahead of Avandia meeting
pharmatimes.com 30.7.2007
FDA questions CV link to Avandia ahead of meeting (...)
The FDA will ask its advisory panel to consider whether the drug's prescribing information should be updated and whether new warnings should be added to Avandia's labelling, though some groups have been calling for a complete withdrawal of the product, a step which is highly unlikely. (...)
Avandia’s safety profile took another bashing on Friday from new research from the UK which suggests that the GSK as well as Eli Lilly/Takeda’s Actos (pioglitazone) double the risk of heart failure, with fluid retention caused by the drugs providing the trigger. Those findings are based on a meta-analysis of more than 78,000 patients, which estimates that one in every 50 patients taking the drugs over a 26-month period will require hospital admission due to heart failure. (...)
FDA Weighs Pulling Avandia Off Market
forbes.com 27.7.2007
WASHINGTON -
The Food and Drug Administration will ask outside experts next week whether the diabetes drug Avandia should be pulled from the market after reviewing studies showing a potential link to increased heart attack risk. (...)
Report Backs Up Warnings About Drug Avandia
nytimes.com 26.7.2007
WASHINGTON, July 26 — Patients who take Avandia, a popular diabetes medicine, face an increased risk of heart attacks while those who take Actos, a similar drug, do not, federal drug reviewers conclude in a new report.
Avandia, made by GlaxoSmithKline, is particularly dangerous to patients who take insulin, the review found, a risk not found with Actos, made by Takeda.
The drugs, which increase the body’s sensitivity to insulin, were each taken by about one million patients last year. (...)
Ahead of the Bell: Glaxo's Avandia
forbes.com 26.7.2007
WASHINGTON -
Government documents due out Thursday will give Wall Street the latest indication of whether GlaxoSmithKline's blockbuster diabetes drug Avandia is headed for new regulatory restrictions. (...)
Bear Stearns analyst Alexandra Hauber cautioned Wednesday that the threat of significant restrictions is real.
"Some seem to assume that Avandia is safe unless the case is proven otherwise," Hauber wrote in a research note. "But the presumption of innocence does not apply to pharmaceuticals."
While FDA is not required to follow the panel's advice, it usually does. (...)
The Nissen Doctrine
forbes.com 24.7.2007
Pharmaceuticals Matthew Herper, 07.25.07, 6:00 AM ET
On Monday, July 30, a panel of academic scientists will meet to advise the U.S. Food and Drug Administration as to what, exactly, the regulator should do about Avandia, the best-selling diabetes drug in the world. (...)
New study slams safety of Glaxo's Avandia drug
reuters.com 17.7.2007
LONDON, July 18 (Reuters) - The safety of GlaxoSmithKline Plc's (GSK.L: Quote, Profile, Research) controversial diabetes drug Avandia was attacked in a new analysis by German researchers on Wednesday, dealing a fresh blow to the group's second-biggest product.
They found little evidence that Avandia improved the quality or length of diabetics' lives and concluded it could actually worsen complications of the disease, after studying pooled data from 18 past trials involving 8,000 patients.
Dr Bernd Richter of Duesseldorf's Heinrich-Heine University, who led the research, questioned whether it was ethical to conduct any further clinical tests with Avandia, since "less dangerous" alternative treatments were available.
Glaxo dismissed his review as misleading and said it strongly disagreed with the conclusions, which were published in the Cochrane Library journal. (...)
GSK defends Avandia over new review - 19/07/2007
pharmatimes.com 19.7.2007
GlaxoSmithKline's controversial diabetes drug Avandia (rosiglitazone) does not have a positive impact on patients' quality of life and is not clinically superior to other antidiabetic drugs, so says a new analysis published by The Cochrane Library this week. But GSK has come out fighting, issuing a statement to say that the limited number of studies evaluated "generate misleading conclusions" and offer "no new evidence" about the drug's use. (...)
Rosiglitazone — Continued Uncertainty about Safety
EDITORIAL
NEJM 2007;357:63-64 (July 5)
(...) As new data about the safety of an approved drug become available, they should not be suppressed. On the contrary, they should be reported to health care professionals, patients, and participants in ongoing clinical trials, even if that means creating uncertainty about the safety of a drug. Although there may be uncertainty about a drug's safety, there should be no uncertainty about the need for open and honest disclosure. (...)
The Record on Rosiglitazone and the Risk of Myocardial Infarction
EDITORIAL
NEJM 2007;357:67-69 (July 5)
(...) Rosiglitazone is also associated with significant weight gain, an adverse effect on low-density lipoprotein cholesterol, an increased risk of heart failure, an increased risk of fractures in women, and an apparent increase in the risk of myocardial infarction.1,2,9,10 Patients should not stop treatment on their own, but if they have concerns, they should consult their physicians. Together, patients and physicians can decide whether they wish to suspend the use of rosiglitazone. (...)
Avandia Fight: Drs. Nissen And Home "Battle" Over Drug
cnbc.com 26.6.2007
(...) Dr. Nissen is one of the world's leading cardiologists from The Cleveland Clinic. He did what's called a meta-analysis (looking at results of more than 40 clinical trials) to glean that Avandia may increase the risk of heart attack and death.
GSK, on the other hand, is in the middle of what's considered to be a gold standard clinical trial designed specifically to measure the cardiovascular side effects of its $3 billion dollar-a-year diabetes drug, Avandia.
But Dr. Nissen told the crowd yesterday he doesn't think that study, known by the acronym RECORD, is up to snuff. "Major errors in design have likely rendered the study futile," he said. (...)
Texas Family Sues GlaxoSmithKline (GSK) Over Man's Heart Attack Death Following Avandia Use (Familie fra Texas saksøker GlaxoSmithKline (GSK) etter at mann døde grunnet hjerteanfall)
drugs.com 20.6.2007
Husband died the same day Avandia heart attack dangers were published
DALLAS, June 20, 2007 /PRNewswire/ -- The widow and son of a Beaumont, Texas, man are suing drug manufacturer GlaxoSmithKline based on claims that the popular diabetes drug Avandia(R) contributed to the man's fatal heart attack.
The lawsuit filed in the United States District Court for the Eastern District of Texas is one of the first against the Philadelphia, Pa.-based pharmaceutical giant since a May 21, 2007, report linked Avandia use to an increased risk of heart attack in patients. (...)
Effekt af rosiglitazon på risiko for AMI og død af kardiovaskulær årsag
Rationel Farmakoterapi nr. 6 (juni 2007)
Rosiglitazon (Avandia) anvendes til behandling af type-2 diabetes. (...)
Der er på det foreliggende ikke grundlag for at fraråde behandling med rosiglitazon, men resultaterne af metaanalysen er tankevækkende.
Første behandling af type-2 diabetes er fortsat metformin og sulfonylurinstof. Behandling med glitazoner medfører øget hyppighed af hjerteinsufficiens, og der er kommet meddelelser om øget hyppighed af frakturer hos kvinder (3).
(...)
FDA places "black box" warning on antidiabetes drugs
BMJ 2007;334:1237 (16 June)
The US Food and Drug Administration has asked the makers of two antidiabetes drugs—rosiglitazone (marketed as Avandia), made by GlaxoSmithKline, and pioglitazone (Actos), made by Takeda—to place "black box" warnings, the most serious kind, on their labels.
The new labels warn of an increased risk of congestive heart failure, because rosiglitazone and related drugs can cause fluid retention. Andrew von Eschenbach, the FDA's commissioner, announced the warning at a hearing of the US House of Representatives' Committee on Oversight and Government Reform last week to examine the FDA's role in evaluating the safety of rosiglitazone.
The new labels do not address the question of whether these drugs pose an increased risk of heart attacks and strokes. (...)
Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes
NEJM 2007;356:2457-2471 (June 14)
(…) Conclusions Rosiglitazone was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that had borderline significance. Our study was limited by a lack of access to original source data, which would have enabled time-to-event analysis. Despite these limitations, patients and providers should consider the potential for serious adverse cardiovascular effects of treatment with rosiglitazone for type 2 diabetes. (…)
GlaxoSmithKline: trouble over Avandia increases
pharmaceutical-business-review.com 13.6.2007
US shareholders have filed a lawsuit against GSK, claiming that the UK drugmaker misled investors over Avandia's safety. Slowing sales of the diabetes drug will impact the company's overall sales performance and although GSK's plans to launch an OTC version of a popular weight-loss pill will go some way to offset these losses, it is unlikely that the drug will sufficiently boost revenues. (...)
Shareholder Lawsuit Caused by GlaxoSmithKline's Avandia Drug
pharmaceutical-int.com 12.6.2007
In the wake of allegations surrounding the harmful effects of its diabetes drug Avandia, GlaxoSmithKline now finds itself being sued by its shareholders. (...)
Although these results were presented to the US Food and Drug Administration in preliminary form in September 2005, and subsequently represented a year later once more established, these, the complaint alleges, were never officially released into the public domain. (...)
GlaxoSmithKline Sued by Shareholder Over Avandia (Update1)
bloomberg.com 11.6.2007
June 11 (Bloomberg) -- GlaxoSmithKline Plc, the world's second-largest drugmaker after Pfizer Inc., was sued by a shareholder claiming the company misled investors about the safety of its diabetes drug Avandia. (...)
FDA scientist says she was reprimanded for warning
usatoday.com 10.6.2007
Rosemary Johann-Liang thought she'd be able to leave her job Friday at the Food and Drug Administration, where she worked for 6½ years, without much fanfare.
"I was trying to leave peacefully," she said in a telephone interview on the eve of her last day as deputy director of the Division of Drug Risk Evaluation, part of the Office of Surveillance and Epidemiology (formerly the Office of Drug Safety). "I had nice parties last week."
But then the popular diabetes drug Avandia began making headlines because a prestigious medical journal aired concerns about its safety. Johann-Liang found herself in the media spotlight.
The reason: She took her staff's advice and recommended in February 2006 that Avandia get a "black box" warning about congestive heart failure. For doing so, FDA staffers told Senate Finance Committee investigators, Johann-Liang was verbally reprimanded and told to talk to her director before making any major recommendations related to drug safety.
FDA spokeswoman Susan Cruzan said Friday that the agency is looking into whether Johann-Liang was reprimanded for her opinion. "We don't know if that's actually the case," Cruzan said. (...)
Drug doubts put lawyers, pharmaceutical companies in motion
chron.com 9.6.2007
Pharmaceutical companies also move quickly when studies hit (...)
The report suggested Avandia, a best-selling diabetes treatment touted in television ads by Della Reese and Jane Seymour, might raise the risk of heart attack by 43 percent and of cardiac-related death by 64 percent. (...)
Settlements become attractive to both sides because pharmaceutical trials are expensive and complex, requiring expert witnesses and detailed records. Fibich said it cost him $1 million to try the first case alleging harmful side effects from the diet drug Fen-Phen.
Only a few lawyers have the talent and the wherewithal to try these cases. (...)
FDA and Glaxo Share Blame for Avandia Disaster
scoop.co.nz 10.6.2007
Opinion: Evelyn Pringle FDA and Glaxo Share Blame for Avandia Disaster (...)
Avandia (rosiglitazone) was FDA approved in 1999 for the treatment of type 2 diabetes, a disease that affects between 18 to 20 million Americans.
When approved, Glaxo promoted Avandia as being safer than Rezulin, a diabetes drug removed from the market in 2000 after serious cases of liver damage developed in patients taking the drug.
Avandia is currently the top selling diabetes drug with total US sales of $2.2 billion in 2006, according to IMS Health, a healthcare tracking information firm. A one-month supply sells for between $90 and $170, the Associated Press reported on May 23, 2007. (...)
(Anm: Chronic liver damage worsened by alcohol-fueled gut bacteria (medicalnewstoday.com 9.2.2016).)
Is Avandia set to be Glaxo's Vioxx?
independent.co.uk 6.6.2007
Sales of Avandia, GSK's blockbuster diabetes pill, have been in sharp decline since a study concluded that it increased the risk of heart problems. Can the drug company launch a fightback to reassure patients and investors about Avandia?
There is no surer sign of a company in crisis mode than a decision to take out full-page adverts in all of America's major newspapers.
At around $100,000 a pop, the ads are an expensive way to try to turn around public opinion - and GlaxoSmithKline had better hope they help. (...)
Pharmaceutical Company Threatened Legal Action Against Physician Who Questioned the Safety of Diabetes Medication Avandia
phoenix.injuryboard.com 7.6.2007
(...) Based upon the sales volume alone, sales of this medication account for a huge source of profit for GlaxoSmithKline. In 1999, apparently after a medical researcher attempted to inform the pharmaceutical company about increased heart risks which have recently been disclosed publicly, company officers allegedly threatened litigation and:
warned him that some executives wanted to hold him accountable for a $4 billion drop in the company's stock.
The medical researcher testified in a congressional hearing this week that he wrote to the company and:
In a letter to SmithKline distributed at the hearing, Buse wrote: "Please call off the dogs. I cannot remain civilized much longer under this kind of heat." (...)
New York Times Examines Drug Company GlaxoSmithKline's Multicultural Advertising for Diabetes Drug Avandia
kaisernetwork.org 7.6.2007
The New York Times on Wednesday examined efforts by GlaxoSmithKline to market its diabetes treatment Avandia to blacks. According to the Times, GSK -- "much more so than any other maker of diabetes drugs" -- "has long placed a marketing focus on" blacks because type 2 diabetes is twice as likely to affect blacks than non-Hispanic whites. (...)
FDA Has Requested Black Box Warnings for Two Diabetes Medications, Agency Commissioner Says at House Committee Hearing
kaisernetwork.org 7.6.2007
FDA has requested a black box warning for the labels of the type 2 diabetes medications Avandia, manufactured by GlaxoSmithKline, and Actos, manufactured by Takeda Pharmaceuticals, because of increased risk for congestive heart failure associated with the medications, agency Commissioner Andrew von Eschenbach announced on Wednesday at a House Oversight and Government Reform Committee hearing, the New York Times reports. FDA issued the request on May 23, according to von Eschenbach. FDA previously had not made the request public (Harris, New York Times, 6/7). (...)
Fireworks fly as lawmakers weigh up Avandia case
pharmatimes.com 7.6.2007
A fiery US House of Representatives committee hearing on GlaxoSmithKline's diabetes treatment Avandia has heard that regulators had decided to call for a strengthening of the drug's label as early as May 23, two days after a meta-analysis called into question the treatment's safety. (...)
F.D.A. Issues Strictest Warning on Diabetes Drugs
nytimes.com 7.6.2007
WASHINGTON, June 6 — The Food and Drug Administration has called for the toughest safety warning on two diabetes drugs, Avandia and Actos, whose health risks have become a focus of Congressional concern. (...)
Diabetes Drug Still Has Heart Risks, Doctors Warn (Diabeteslegemiddel har fortsatt hjerterisiko, advarer leger)
nytimes.com 6.6.2007
A medical study intended to demonstrate the heart safety of a well-known diabetes treatment seems, instead, to have added to the controversy over the drug.
Its manufacturer, GlaxoSmithKline, says preliminary results of the clinical trial provide reassurance that the drug, Avandia, an oral medication for Type 2 diabetes that has been used by an estimated seven million people worldwide, does not raise the risk of a heart attack or death from cardiovascular disease.
Influential doctors said that the data published online yesterday in a major medical journal did nothing to ease their concerns about the heart risks. The doctors raised their concerns in three editorials accompanying the Avandia study in The New England Journal of Medicine. (...)
Avandia's Fine Print
forbes.com 6.6.2007
(...) It might come as a surprise to know, then, that a warning about the risk of heart attacks was already in the FDA-approved product labeling. But it was buried in the fine print, on page 15 of the label.
The exact wording: "In these clinical studies an increased incidence of edema, cardiac failure and other cardiovascular adverse events was seen in patients on Avandia and insulin combination therapy compared with insulin and placebo."
When being questioned, FDA head Andrew Von Eschenbach became a little flustered and was unable to find the warning in the Physician's Desk Reference. When he finally did find it, Rep. Stephen F. Lynch, D- Mass., was incredulous about the text of the warning.
"You are not seriously suggesting that it is the warning?" Lynch said. "This is really absurd, this is ridiculous that you are saying this is a warning." (...)
Lawmakers to grill Glaxo, FDA on diabetes drug
reuters.com 6.6.2007
WASHINGTON (Reuters) - U.S. health officials and drugmaker GlaxoSmithKline Plc are likely to face tough questioning from lawmakers on Wednesday over their handling of data suggesting a heart risk with the widely used diabetes pill Avandia (...)
GlaxoSmithKline steps up defence of Avandia – report
euro2day 6.6.2007
LONDON (Thomson Financial) - GlaxoSmithKline PLC has stepped up its defence of Avandia, the diabetes medicine, after the release of fresh data last night that the company claimed showed little significant difference between the drug''s safety record and that of other common diabetes treatments, The Times reported.
However, critics said that the results were inconclusive and would not end the debate surrounding the drug''s alleged link with an increased risk of heart problems, acvcording to the newspaper. (...)
Medical Expert to Testify Against Glaxo
forbes.com 6.6.2007
The controversy surrounding GlaxoSmithKline's diabetes drug Avandia mounted Wednesday as a medical expert prepared to tell lawmakers the British drug maker threatened him with legal action when he first raised questions about the treatment's safety. (...)
GlaxoSmithKline response to New England Journal of Medicine editorials
gsk.com 5.6.2007
PHILADELPHIA, PA June 5, 2007 The following is GlaxoSmithKline’s [NYSE:GSK] response to editorials written in the New England Journal of Medicine (NEJM) regarding Avandia® for the treatment of type 2 diabetes.
We believe the NEJM editorials are selective in their use of data to support a biased view, and therefore do a disservice to patients, physicians, science and public health. (...)
Glaxo defends Avandia with full-page newspaper ads
reuters.com 5.6.2007
NEW YORK (Reuters) - GlaxoSmithKline Plc fired another salvo in defense of diabetes treatment Avandia on Tuesday by taking out full-page advertisements in at least a dozen major U.S. newspapers in an attempt to reassure patients of the safety of the widely used medicine. (...)
FDA to Form Communication Experts' Panel
forbes.com 4.6.2007
Associated Press Associated Press 06.04.07, 12:45 PM ET
The Food and Drug Administration said Monday it will name a panel of experts to help better communicate with consumers about problems with drugs, food and other products.
The announcement comes as the agency braces for new criticism over how it handled public communications after a recent medical journal article revealed GlaxoSmithKline (nyse: GSK - news - people)'s diabetes drug Avandia may increase the risks of heart attack.
The British drug maker said it provided information cited in the article to the FDA last August. Lawmakers in the House say they plan to investigate why the FDA did not notify doctors and patients about the information earlier. (...)
Avadia puts FDA in spotlight
nj.com 3.6.2007
Heart risks tied to diabetes drug fuels debate on safety, vigilance (...)
Congressional Hearings on Prescription Drug Safety Could Highlight 'Dissention' Among FDA Officials (Kongresshøringer om reseptbelagte legemidler kan rette oppmerksomhet på "dissens" mellom ledere i FDA)
Capitol Hill Watch
kaisernetwork.org 31.5.2007
A House hearing on June 6 to examine FDA's regulation of prescription drugs in the wake of recent safety concerns "may highlight the growing internal dissension between officials who approve drugs and those who track the safety" of approved drugs, the New York Times reports. The Times notes that tension between the drug approval office and drug safety office "has long been common, but in recent months it has erupted into sniping," particularly during an advisory committee hearing last month on Merck's arthritis drug Arcoxia. (...)
Avandia Critic Claims FDA Smear Campaign (Kritiker av Avandia hevder FDA står bak svertekampanje)
abcnews.go.com 30.5.2007
Cardiologist 'Not Backing Down' After Alleged Media Attack by an FDA Spokesman
A study co-authored by Dr. Steven Nissen reported that diabetes patients who took Avandia, made by GlaxoSmithKline, may be more likely to have a heart attack than patients who took other medications or a placebo.
The prominent cardiologist sounding alarms about the diabetes drug Avandia claims he is the target of a smear campaign organized by a top Food and Drug Administration (FDA) spokesman.
Dr. Steven Nissen, chairman of Cardiovascular Medicine at the Cleveland Clinic, showed ABC News an e-mail sent to several health reporters by Douglas Arbesfeld, a senior communications consultant to the FDA.
In the e-mail, entitled "What are St. Steven's feet made of? Clay, perhaps?," Arbesfeld forwarded to reporters a critical news article which included an anonymous blog accusing Nissen of playing favorites among drug companies. (...)
FDA Head Defends Working With Companies
forbes.com 30.5.2007
Associated Press The head of the Food and Drug Administration on Wednesday deflected criticism of his agency's coziness with industry and defended a recent decision not to require new warning labels on a GlaxoSmithKline diabetes drug that may substantially raise the risk of heart attack. (...)
Did the New England Journal of Medicine Really Commit "Journalistic Malpractice"? And Who Says So?
hcrenewal.blogspot.com 30.5.2007
The publication of a meta-analysis which suggested that rosiglitazone (Avandia, made by GlaxoSmithKline [GSK]) may increase cardiac risk has created quite a kerfuffle. (See our posts here and here. The meta-analysis is Nissen SE, Wolski K. Effects of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007; 356, online here) (...)
GlaxoSmithKline says data back Avandia safety profile
marketwatch.com 30.5.2007
Wednesday said additional data from several large clinical trial support the safety profile of diabetes drug Avandia, its second-best selling product.
The U.K. drugmaker said the drug's side effects, highlighted in a recent article published in the New England Journal of Medicine, are comparable to those seen with two other widely used diabetes medicines, metformin and sulfonylurea.
A recent New England Journal of Medicine article, based on an analysis of a number of clinical trials, suggested Avandia could increase the risk of heart attacks by 43% and death from other cardiovascular causes by 64%. (...)
Avandia Still Cardiac Risk Seven Years After Initial Warning
the-injury-lawyer-directory.com 29.5.2007
(...) events" among patients taking the drug.
Both the FDA and the maker of Avandia (GlaxoSmithKline) have known about the risks associated with the drug for seven years but have not adequately warned prescribing doctors and consumers about the deadly effects of the drug.
In 2006, worldwide sales of Avandia exceeded $3 billion, making it one of GlaxoSmithKlines best-selling drugs ever. Clearly, the maker of Avandia will lose quite a bit of money each year if and when Avandia is recalled. (...)
GlaxoSmithKline Slips on Avandia Fallout
forbes.com 29.5.2007
(...) "This reaction is far worse than we had anticipated and suggests that there could be as much as 22 percent downside risk to GSK's near-term earnings, suggesting that there is still further downside to GSK's share price," Deutsche Bank (nyse: DB - news - people) analysts said in a not. (...)
Researchers Find Deadly Prescription Drug Effects Six Years Before FDA
sciencedaily.com 29.5.2007
Science Daily — Northwestern University's Charles Bennett, M.D., is a super sleuth of potentially deadly prescription drug reactions. He leads a national SWAT team of doctors called RADAR (Research on Adverse Drug Events and Reports) based out of Northwestern's Feinberg School of Medicine. They swoop in to investigate early signs of trouble years before the Food and Drug Administration (FDA) takes notice. (...)
GSK admits to diabetes drug risk (GSK innrømmer risiko for diabeteslegemiddel)
cctv.com 28.5.2007
China's medical director for U.K's pharmaceutical giant GlaxoSmithKline admitted on Saturday that the company's widely promoted diabetes drug, Avandia, could create risks to a patient's heart by as much as 30 percent.
But the company denied the recent conclusion made by the authoritative New England Journal of Medicine. The Journal had claimed that the heart risk associated with the drug was about 43 percent. (...)
Safety concerns on GSK's Avandia may have `class effect'
moneycontrol.com 28.5.2007
Safety-concerns over GlaxoSmithKline's diabetes drug Avandia, after reports linked it to a potential heart risk, have brought back memories of Merck's arthritis drug Vioxx (Rofecoxib), globally recalled in 2004. (...)
Test of Drug for Diabetes in Jeopardy
nytimes.com 26.5.2007
A large clinical study meant to test the heart safety of the diabetes treatment Avandia may be in jeopardy as a result of recent reports of the drug’s risks, according to an executive at its maker, GlaxoSmithKline.
Dr. Ronald L. Krall, the medical director for GlaxoSmithKline, said in a telephone interview yesterday that some of the 4,450 patients enrolled in the drug trial, called Record, have dropped out this week because of safety concerns about Avandia. (...)
Study indicates diabetes drug linked to cardiovascular death
BMJ 2007;334:1073 (26 May)
(...) The analysis by Steven Nissen and Kathy Wolski, of the Cleveland Clinic, Cleveland, Ohio, included 15 560 patients randomly assigned to regimens that included rosiglitazone, and 12 283 patients assigned to regimens that did not. The mean age of patients was 56 years, and the mean baseline glycated haemoglobin concentration was about 8.2%.
Patients receiving rosiglitazone had an odds ratio for myocardial infarction of 1.43 (95% confidence interval 1.03 to 1.98, P=0.03). The odds ratio for death from cardiovascular causes was 1.64 (0.98 to 2.74, P=0.06). (...)
Ignoring the Warnings, Again? (Ignorerer advarslene, nok engang)
EDITORIAL
nytimes.com 25.5.2007
The latest findings on Avandia, a top-selling diabetes drug, raise concerns both about its safety and about the way the manufacturer and the Food and Drug Administration have responded to signs of danger. It would be rash to make definitive judgments until the F.D.A. completes a detailed analysis. But the handling of this case bears disturbing resemblances to the Vioxx debacle, in which early warning signs were ignored by its manufacturer until the evidence of serious harm became inescapable and the drug was pulled from the market. (...)
Risky drugs prompt questions, concerns
elpasotimes.com 24.5.2007
How does a drug go from blockbuster to bust?
How can big safety problems go undetected in medicines taken by millions of people for many years, as happened this week with the diabetes pill Avandia and a few years ago with the painkiller Vioxx?
Or with devices like drug-coated stents, which came under a cloud last year after 6 million heart patients had already received them? (...)
Latest drug scare shows need for FDA overhaul
yahoo.com 23.5.2007
Americans ought to be able to feel secure that the medications they take are thoroughly monitored for safety before and after the drugs hit the market. After all, there's a government agency - the Food and Drug Administration -which does that.
Or does it? (...)
Avandia risks exposed under deal to post data
fiercebiotech.com 23.5.2007
GlaxoSmithKline's current woes over a new study linking Avandia to increased cardiac risks among diabetes patients can be attributed to the push for more public disclosure of trial data. Glaxo's settlement agreement three years ago with the state of New York included its agreement to publicly disclose more of its data. (...)
- here's the report on Avandia from The New York Times
ALSO: Public Citizen claims that U.S. regulators were aware of Avandia heart risks five years ago. Report
PLUS: Swiss regulators have approved Glaxo's breast cancer therapy Tykerb. Report (...)
Congress To Examine FDA's Handling of GlaxoSmithKline's Diabetes Drug
seekingalpha.com 23.5.2007
Mark S. Senak submits: I don't know what the record is for announcing a Congressional investigation after breaking news, but the title may go to Congressman Henry Waxman (D-CA), under whose feet no grass grows. I think he may hold the record. (...)
Analysis: Allegations fuel Avandia fire
upi.com 23.5.2007
WASHINGTON, May 23 (UPI) -- The controversy over whether GlaxoSmithKline's diabetes drug Avandia increases the risk of heart problems heated up Wednesday, with allegations the Food and Drug Administration was concerned about the danger years ago, but never took any action. (...)
GlaxoSmithKline says sales of diabetes drug could bounce back after safety scare
iht.com 23.5.2007
LONDON: GlaxoSmithKline PLC Chief Executive Jean-Pierre Garnier said Wednesday it is "very possible" that sales of its diabetes drug Avandia could regain lost ground once safety data the company expects to vindicate the treatment becomes available.
Analysts expect Avandia sales to drop sharply after an article combining results from dozens of studies published in The New England Journal of Medicine on Monday that said people taking the drug have a 43 percent greater risk of heart attack than patients using other diabetes drugs, or no medication.
Glaxo said its own reviews showed the drug increased the risk of heart attack by 30 percent, and said it told the U.S. Food and Drug Administration about that last year. The British drug maker added that it disagreed with the article's conclusions and questioned its methodology.
Garnier acknowledged at the company's shareholder meeting on Wednesday that sales of Avandia could fall, but said that it is too early to predict whether the drug will be the target of product liability lawsuits. (...)
Diabetes-medisin kan gi hjerteproblemer
helserevyen.no 22.5.2007
En ny undersøkelse avdekker at diabetes-medisinen Avandia gir økt risiko for å dø av hjerte- og karsykdommer. I USA krever medisinske eksperter at legemidlet tas av markedet. (...)
Legemiddelselskapet GlaxoSmithKline, som produserer Avandia, har angrepet studien og beskrevet den som en inkompetent analyse av data fra studier det er vanskelig å kombinere. Selskapet omsatte Avandia for hele 2,8 dollar i fjor.
Amerikanske politiske myndigheter tror Avandia kan knyttes til opp til 11 600 hjerteanfall per år i USA alene.
En annen side ved saken er at FDA er kommet i vanry som uegnet til å ivareta befolkningens sikkerhet.
Avandia har vært på blå resept i Norge siden 2004. (...)
Avandia
Open-Source Drug Safety?
forbes.com 22.5.2007
In fall 2005 and again in August 2006, GlaxoSmithKline shared shocking news with the Food and Drug Administration. When 42 different studies of its diabetes drug Avandia were combined, the drug appeared to raise patients' chances of having a heart attack by 30%. (...)
This story has repeated again and again over the past six years. An independent doctor assembles all the available data on a drug or medical device, and finds it dangerous. Vioxx was among the first drugs felled this way (Nissen co-wrote that analysis.) J&J's (nyse: JNJ - news - people) Natrecor, for heart failure, saw its sales plummet after to cardiologists called its safety into question. Pargluva, from Bristol-Myers Squibb (nyse: BMY - news - people), was never approved after such an analysis. It was an analysis of published clinical trials that raised the first big questions about drug-coated stents causing heart attacks in rare cases.
Now, this kind of pharmaceutical vigilantism is set to become the order of the day. Both houses of Congress are expected to pass laws that tweak the way the FDA monitors the safety of new medicines after they are approved. Many of the most radical changes, like a proposal to restrict TV ads and a push from Grassley to set up a separate FDA division to monitor side effects, didn't make it into the Senate version. But the bill would compel drug firms to make all of their data available on public Web sites. That, in turn, would let academic watchdogs like Nissen troll for side effects more easily.
It's an open source approach to drug safety. (...)
Stor økning i salg av Actos og Avandia
legemiddelverket.no 2.1.2005
(...) Salg av Avandia i fjerde kvartal 2003 var omlag 40 000 DDD, mens salg i fjerde kvartal i 2004 var omlag 180 000 DDD, altså en økning på omlag 350 prosent. I samme tidsrom er det en dobling av salg av Actos.
Økningen i fjerde kvartal antas å være en følge av at preparatene ble tatt opp på blå resept i dette tidsrommet. (...)
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