Avandia Raises Heart Risk, FDA Panel Finds

WEDNESDAY July 14, 2010 -- A U.S. government advisory panel weighing the fate of the diabetes drug Avandia has voted that the medication does raise users' odds for heart attack more than other medications of its kind but does not increase the risk of death.

A decision on whether or not the drug should be banned from the market is expected by late Wednesday at the end of the two-day meeting.

According to the New York Times, 18 members of the U.S. Food and Drug Administration panel voted Wednesday afternoon that Avandia might up the risk of heart attack, six said they weren't concerned about a raised risk, while nine said they were unsure.

On their second vote, however, only one member of the committee thought that Avandia increases the risk of death when compared with older medicines, 20 said it did not increase the risk of death, and 12 remained unsure.

The panel seemed more decided when comparing Avandia's safety risks to its sister medication, Actos. Twenty panel members voted that Avandia was more likely to cause heart attack than Actos, 4 voted that it was no more likely to do so, and 8 said they didn't know, the Associated Press reported.

The final vote could still go either way, said Dr. Alan Kadish, president and CEO of Touro College, based in New York City and operator of several medical colleges. But he added, the fact that the committee overall did not think the drug increased the risk of death and the fact that so many people are taking it indicated there might be "a small preference for keeping it on the market."

The committee has been meeting intensively since early Tuesday morning, hearing differing opinions not only from outside experts and pharmaceutical representatives but also from within the FDA itself.

The safety of the blood-sugar-lowering drug, part of the thiazolidinedione family, has been in question for years.

In 2005, the FDA asked Avandia's maker, GlaxoSmithKline (GSK), to conduct a meta-analysis of all its clinical trials on the drug.

The analysis, which did show a signal of increased risk of heart attack, was submitted to the FDA the following year.

FDA then did its own analysis while a number of other trials came out also showing signals of heart troubles.

In November of 2007, FDA added a boxed warning to the drug saying that there was a potential risk of increased cardiovascular ischemic events with Avandia.

The current expert panel is focusing much of its attention on the results of the highly publicized RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes), announced in June of 2009. It found that Avandia significantly raises the risk of heart failure (and bone fractures) though not cardiovascular disease or death.

Both Avandia and Actos, which is made by Takeda, came with warnings regarding heart failure when they were first approved.

The drama intensified considerably just before the advisory meeting began. Last Friday, an FDA official posted statements on the agency's web site questioning the design and interpretation of the pivotal RECORD trial.

Then in a report released early Tuesday, the Times said that GSK knew more than a decade ago that Avandia caused an increased risk of heart problems but covered up the information.

Glaxo, in a prepared statement, said that, "The RECORD study was conducted according to good clinical practices and the data are reliable. . . RECORD demonstrated that Avandia was not associated with an overall increase in cardiovascular hospitalization or cardiovascular death compared to [diabetes drugs] metformin and sulfonylureas."

The committee's options, according to statements made by Dr. Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, at a Thursday teleconference "range from allowing the continued marketing of Avandia and revising the label to remove the boxed warning all the way to withdrawal from the U.S. market."

The FDA is not obligated to follow the recommendations of its expert panels, but it usually does.

More information

There's more on the thiazolidinedione class of diabetes drugs at the U.S. National Library of Medicine.

Posted: July 2010


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