MinTankesmie

Avandia (rosiglitazone) - informasjon versus kunnskap og visdom - hvem visste hva?

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).)

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 noen 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 analysere 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: Noen 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 (...)

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." (...)

(Anm: Association between industry affiliation and position on cardiovascular risk with rosiglitazone: cross sectional systematic review. BMJ 2010;340:c1344 (18 March).)

(Anm: Sakkyndige legers integritet, partiskhet og habilitet versus løgn i rettssalen (sakkyndighet) (mintankesmie.no).)

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.)

(Anm: Association between industry affiliation and position on cardiovascular risk with rosiglitazone: cross sectional systematic review. BMJ 2010;340:c1344 (18 March).)

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. (...)

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 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 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