Three years ago, in one of the more notable drug-safety scandals in recent history, the diabetes drug Avandia was all but banned from use in the United States after researchers found that thousands of people had heart problems after taking it. Today, it is a drug of last resort for people with diabetes who are so sick that a heart attack is worth the risk.
But now, in a highly unusual move, the Food and Drug Administration has decided to reopen the case on Avandia and will ask a panel of experts this week whether the agency must reconsider the restrictions on the drug.
That is just one of several options before the advisory committee, but lifting the limits would amount to a major policy reversal and could be a huge victory for the drugs maker, GlaxoSmithKline, which has its U.S. headquarters in Research Triangle Park. Avandia was once a top-selling drug, reaching more than $3 billion in sales in 2006 before controversy flared. It could also help rewrite one of the most embarrassing chapters in the FDAs recent history.
But critics, like Dr. Steven Nissen, the Cleveland Clinic cardiologist who was the first to sound a public alarm about the drug, say it is far too dangerous to use in diabetes treatment. He said an analysis of more than 50 studies linked Avandia to an elevated risk of heart attack; one study linked the drug to more than 47,000 cases of heart attack, stroke or heart failure from 1999 to 2009.
Nissen and others contend that the FDAs decision to revisit the drug is more about saving face than protecting patients. The efforts to whitewash this entire affair is really an unacceptable misuse of their regulatory role, Nissen said. He added 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.
Dr. Janet Woodcock, the FDAs top drug official, said the two-day meeting that begins Wednesday was convened to weigh a review she requested in 2010 of an earlier clinical trial that GSK itself had conducted. Past findings were riddled with questions, she said, and the agency has an obligation to try to answer them.
I made the decision last time about Avandia, and its not that it was an open-and-shut case, she said in an interview. What were trying to do here is resolve that uncertainty as much as we can with all the available data.
The FDA typically follows the recommendations of its advisory panels. While experts said widening access to the drug would be unlikely, many found it puzzling that it was even under consideration. The process and its outcome are likely to be among the most closely watched drug-safety cases in recent years.
Avandias troubles began in 2007, eight years after it was approved by the FDA, when 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 agencys oversight of prescription drugs. It has reshaped the regulatory landscape for diabetes drugs at a time when an estimated 26 million Americans have the disease: Companies are now required to show that new drugs do not hurt the heart.
In 2010, European regulators removed Avandia from the market, and its use was severely restricted in the United States. The loss of sales led to lay offs at GSK, including in Zebulon where the drug was packaged. That year, the FDA ordered an outside review of GSKs 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 GSKs website, the review found previously unreported cases of heart complications and deaths, but not enough to change the GSK trials conclusions that Avandia did not significantly raise the risk of cardiovascular harm. However, some outside experts have said that the GSK trial was seriously flawed. Some also question the independence of the Duke review, which was paid for by GSK.
In 2012, GSK reached an agreement with the 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. Dr. Murray Stewart, a senior vice president at GSK, rejected criticisms of the companys 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. Its the most robust evidence weve got, he said.
He said the analysis confirmed the companys longstanding position that Avandia was safe, but declined to say whether GSK would support lifting the restrictions. I think thats speculation at this stage, he said.
News & Observer staff writer Mary Cornatzer contributed