She says the company looks forward to “participating in a rigorous scientific discussion of the data on the cardiovascular safety of Avandia with the FDA advisory committees.”
Nissen called the upcoming FDA hearing a litmus test for the administration.
“This is a defining moment now for the new leadership for the FDA,” he says. “Will they act decisively? We have people with a public health background now heading up the FDA. Will it be enough to overcome the inertia and get the drug off the market?”
Avandia is reportedly at the center of a furious debate within the FDA, with some officials calling for its removal from the market and others arguing the risks are not proven.
After Nissen’s 2007 study, an FDA advisory panel said that Avandia does raise risks to the heart but voted to keep it on the market. A few months later the agency added a black-box warning about potential heart risks of the drug.
In 2009 about 2 million prescriptions for Avandia costing $663 million were sold in the United States, about a fifth of its peak sales of $3.2 billion in 2006.
Earlier this year, the Senate Committee on Finance reported that GlaxoSmithKline misrepresented findings that the drug may increase cardiovascular risk and “sought ways to downplay findings that a competing drug might reduce cardiovascular risk.”
At the time, the company disagreed with the Senate’s conclusions and pointed out that the FDA had decided the drug should remain on the market based on all the available evidence.
Avandia the new Vioxx?
Graham has been an outspoken critic of the FDA’s process for evaluating drugs’ safety once they are on the market. His estimates of the dangers of the arthritis drug Vioxx were instrumental in its demise. He compares Avandia to Vioxx, the drug that Merck finally pulled from the market after studies showed it increased the risk of heart attack and strokes.
“The people who put Avandia on the market are the people responsible for deciding whether Avandia stays on the market or leaves the market. The country was defenseless against another Vioxx,” Graham says.
Sidney Wolfe, M.D., director of Public Citizen’s Health Research Group, a consumer watchdog group, says the FDA has been “absolutely reckless” in delaying decisive action because of the “overwhelming evidence” that Avandia is dangerous and—importantly—has no benefit over alternative drugs.
Wolfe is on the FDA’s drug safety advisory committee, but he is not going to take part in its upcoming meeting because of Public Citizen’s 2008 petition to the agency to withdraw the drug from the market.
Wolfe and others have also called on the FDA to halt a large-scale clinical trial, known as the TIDE trial, testing the safety of Avandia. The trial, originally requested by the FDA, is set to recruit 16,000 patients at hundreds of sites around the world.
Karen Riley, an FDA spokesperson, says the two new studies published today are “part of a much broader FDA evaluation of the available data” that will be presented at the joint meeting of two FDA advisory committees. Scientists at the meeting will present their evidence and their views on the safety of the drug.
“Drug safety is a core charge for the FDA,” Riley says. Although the agency only approves drugs for the market after it has decided that the benefits of the drug outweigh any risks, safety issues can emerge “because the real world is simply different from the world studied in a clinical trial.”
Riley says the agency will act as quickly as it can after this month’s advisory committee meeting. “More data has been flowing in, and the right way to handle it is to have a vigorous scientific discussion, which we are going to have,” she says.
Nathan of Harvard says after Nissen’s 2007 study in the New England Journal of Medicine and other research called into question Avandia’s safety, many doctors stopped prescribing it. He says he presumes many current Avandia prescriptions are for patients already taking the medication.
“Whether there are new prescriptions being written for that is a real issue,” he says. “It just doesn’t seem sensible to me.… It’s a triumph of advertising over maybe common sense.”
Elizabeth Agnvall is a contributing editor at the AARP Bulletin. Katharine Greider, who lives in New York and writes about health and medicine, contributed to this story.