Avandia Survives

GlaxoSmithKline's Avandia should remain on the market--but with new warnings. That was the 21-1 vote recommendation of a joint meeting of FDA's Endocrinologic and Metabolic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee, which met July 30 to consider the fate of the drug. Avandia (rosiglitazone) has been under fire since a study in the May 21 New England Journal of Medicine (NEJM) found that the diabetes drug--GlaxoSmithKline's second-best seller--substantially increased the rate of heart attack in patients that took it.

"The advisory committee recommended additional warnings, some suggesting a boxed warning," said Robert J. Meyer, MD, director of FDA's Office of Drug Evaluation II for the Center for Drug Evaluation and Research, in a press conference following the meeting. "Likewise, there were many who recommended limiting the use of the drug with insulin and in patients with severe heart disease, but many did not specifically cite a firm contraindication. FDA will take this advice into due consideration in reaching its internal decisions on how to best respond."

As many observers had expected, a substantial part of the presentation on the drug was devoted to critiquing the data. Questions were raised about both the meta-analysis by controversial cardiologist Steven Nissen, which formed the basis of the NEJM article, and GSK's record study, which painted the most favorable picture of rosiglitazone.

"The reason you see this repeatedly at the advisory committees is if we have a clear answer, we don't take the issue to the advisory committee," said Meyers. "Part of the problem with some of the long-term randomized control trials here is they were not specifically designed to answer this question. If we had the foresight eight years ago to have known that, in 2007, we'd be grappling with this, this would've been a different issue."

GSK spokeswoman Mary Anne Rhyne estimated that 1 million patients were currently taking Avandia. She said that she could not speculate on the future sales of Avandia following the allegations cited in the NEJM article but stated that GSK had agreed to look at the totality of the data.

"We've already studied 1.3 million patients in a clinical setting to evaluate Avandia's effectiveness, and it's clear to us that there is a need for Avandia as a treatment option," Rhyne said. "It's interesting--there were a number of patients at the hearing speaking about how difficult it is to control diabetes. One was an amputee, and one had lost his vision because of diabetes. And they were asking for the availability of options to control the effects of diabetes."

In terms of making a final decision regarding Avandia, Meyer said: "The FDA will consider the advice in an expedient manner and move forward accordingly on this important matter, but there is no set time frame."

Although FDA is not required to follow the advice of its advisory panels, historically, it has done so.