FDA Staff Cite Avandia Concerns, As Advisory Panel Prepares to Discuss Drugâ€™s FateJul 9, 2010 | Parker Waichman LLP
Avandia continues to raise safety concerns with staff at the Food & Drug Administration (FDA), according to a 756-page briefing posted on the agency’s Website. The documents were posted in advance of an advisory panel meeting next week that could help determine whether or not Avandia, known generically as rosiglitazone, will stay on the market.
According to The Wall Street Journal, one of the documents included in the posting is a memo discussing the RECORD trial, an Avandia study paid for by GlaxoSmithKline, the manufacturer of the controversial diabetes drug. RECORD, which involved 4,500 patients, compared Avandia to patients receiving other diabetes drugs, metformin and sulfonylurea, for an average of 5.5 years. Released in 2009, RECORD did not show an increased heart-attack risk that has been seen in some other Avandia studies.
According to the Journal, the memo included in the FDA briefing was written by Thomas Marciniak, a medical team leader in FDA’s division of cardiovascular and renal products. He writes that RECORD was “inadequately designed and conducted to provide any reassurance about the CV (cardiovasular safety) of rosiglitazone.” He goes on to write that the RECORD results “confirm and extend the recognized concerns regarding heart failure” and possibly suggest an increased risk for heart attacks, the Journal said.
In addition to the RECORD study, the FDA advisory panel scheduled to meet next week will also look at a study conducted by Dr. David Graham of the FDA’s Center for Drug Evaluation and Research. It found that patients in the U .S. Medicare system who took the drug may have suffered as many as 48,000 heart attacks, strokes and other problems between 1999 and 2009. Graham’s study involved 227,500 patients, making it the largest to date, and found that patients who took Avandia were 27 percent more likely to suffer a stroke, 25 percent more likely to develop heart failure and 14 percent more likely to die compared with those who took another drug called Actos.
According to The Wall Street Journal, the FDA advisory panel will be asked to vote on several actions the FDA could take in regards to Avandia. These include allowing the product to stay on the market or adding restrictions on the use of the product such as only allowing certain doctors to prescribe the medication. The meeting will take place over two days, and the vote will occur next Wednesday. While the FDA is not required to follow the advise of such panels, it usually does so.
Avandia has been the subject of safety concerns for several years. In November 2007, a black box warning – the FDA’s strongest safety warning – detailing Avandia’s association with myocardial ischemia was added to the drug’s labeling. The black box was added after the Cleveland Clinic published a meta- analysis of 42 clinical trails that showed patients taking Avandia had a 43-percent higher risk of having a heart attack.
Last week, Dr. Stephen Nissan, who conducted that study, released a follow-up to it. The update looked at 56 clinical studies involving 35,500 patients, including RECORD, and found an increased heart attack risk of 28 percent. Without RECORD, the risk of heart attacks rose to 39 percent, according to study.
Since November 2007, Avandia’s label has included a black box warning – the FDA’s strongest safety warning – detailing Avandia’s association with heart attacks. The black box didn’t satisfy many Avandia critics, however, who continue to advocate that it be pulled from the market.