In 2010 the drug Avandia (rosiglitazone) was restricted in the US and banned in EU, after researchers found that patients were possibly subject to increased risk of heart problems after taking it. Today, Avandia is a drug of last resort in many parts of the World for people with diabetes who are so sick that a heart attack is worth the risk.
In a highly unusual move, the Food and Drug Administration has decided in April to reopen the case on Avandia and will ask a panel of experts next week whether the agency must reconsider the restrictions on the drug.
Lifting restrictions would amount to a major policy reversal and could be a huge victory for the drug’s maker, GlaxoSmithKline. Avandia was once a top-selling drug, reaching more than $3 billion in sales in 2006 before the controversy started. It could also have consequences on Europe’s EMA’s position on the drug.
In 2010, European regulator EMA withdrew Avandia from the market, and its use was severely restricted in the United States. That year, the F.D.A. ordered an outside review of Glaxo’s clinical trial, which had lasted six years and whose results were published in 2009. It is that review, conducted by researchers at Duke University, that experts are being asked to consider this week. According to a preliminary summary posted on Glaxo’s Web site, the review found previously unreported cases of heart complications and deaths, but not enough to change the Glaxo trial’s conclusions that Avandia did not significantly raise the risk of cardiovascular harm. However, some outside experts have said that the Glaxo trial was seriously flawed. Some also question the independence of the Duke review, which was paid for by Glaxo.
Critics, like Dr. Nissen and others state that the F.D.A.’s decision to revisit the drug is wrong and that he would be “horrified” if the panel were to recommend that the restrictions be removed. “The evidence against this drug is overwhelming,” he said.
Avandia’s troubles began in 2007, eight years after it was approved by the F.D.A., when Dr. Nissen published evidence showing that the drug raised the risk of heart attack by more than 40 percent. A Senate inquiry ensued, and the episode exposed what many said were serious gaps in the agency’s oversight of prescription drugs.
In 2012, Glaxo reached an agreement with the US federal government to pay $3 billion in fines because of practices involving several drugs, including a failure to report safety updates about Avandia. The settlement was the largest ever involving a pharmaceutical company. Some researchers who served on previous panels asked why the agency would reopen the book on a drug that everyone thought had been closed. Some other experts said there was value in reviewing the trial. Dr. Sanjay Kaul, a cardiologist who served on the 2010 panel, said previous studies of Avandia’s heart risks were of lesser quality than the Glaxo clinical trial that is being re-evaluated.
Dr. Murray Stewart, a senior vice president at Glaxo, rejected criticisms of the company’s trial or the review, saying that the Duke researchers had been independent and that the company had handed over files on more than 4,000 people involved in the trial. “It’s the most robust evidence we’ve got,” he said. He said the analysis confirmed the company’s longstanding position that Avandia was safe, but declined to say whether Glaxo would support lifting the restrictions. “I think that’s speculation at this stage,” he said.