WASHINGTON – Two scientific studies published today are reinforcing serious health warnings about a heavily marketed diabetes drug, Avandia, which is manufactured by GlaxoSmithKline.
The studies increase the pressure on the Food and Drug Administration as the agency prepares for a meeting July 13 to consider halting a controversial clinical trial and withdrawing the drug from the market.
“We are taking the question of Avandia safety very seriously,” Dr. Joshua M. Sharfstein, the FDA’s principal deputy commissioner, said in response to the new studies. He declined to discuss details.
“I don’t want to pre-judge the full scientific debate that is going to happen” on July 13, he said.
GlaxoSmithKline said in a brief statement that its analysis of the accumulating research shows that its drug carries no greater risk.
Avandia and a competitor drug, Actos, which is manufactured by Takeda Pharmaceutical Co., of Japan, are prescribed to treat type-2 diabetes which typically strikes people who are overweight. The drugs work by making the body more sensitive to insulin.
Actos has not been associated with the same negative health effects, however, leading to questions about why FDA should allow Avandia to remain on the market when there is an apparently safer drug that treats the same problem.
In one of the two studies released today, a review by government researchers of data for 227,000 Medicare patients taking either Avandia or Actos found that Avandia increased the risk of heart attack, stroke, heart failure, or death by 17 percent. The study was published today in JAMA, the Journal of the American Medical Association.
One of the researchers on that study wrote an email to FDA officials earlier this month that the study indicated that Avandia caused an estimated 48,000 additional cardiovascular events among Medicare patients.
“Look at our study, and then ask yourself, ‘Why would you want to take Avandia?’” Dr. David Graham, the FDA’s co-author who has urged the agency to force the drug off the market, said in an interview.
The second study was performed by Cleveland Clinic cardiologist Dr. Steven Nissen, who was the first to publish a broad analysis of clinical trials in 2007 that said Avandia raised the risk of a heart attack.
Nissen’s study published today in the Archives of Internal Medicine, analyzing outcomes of 56 separate clinical trails involving 35,000 patients, confirms those findings of three years ago. The study found elevated risk of heart attack of 28 to 39 percent.
The growing body of evidence, and FDA’s evolving response, is reminiscent of the controversy leading up to Merck’s withdrawal of Vioxx in 2004. But a key difference, say specialists, is that Vioxx was taken to control pain across a healthier population. Type-2 diabetes patients are far sicker, so an increase in cardiovascular risk carries even greater impacts.
“When you have a drug that increases heart attack by a third in diabetics, it has enormous public health consequences, so it is obviously very concerning,” Nissen said in an interview.
Nissen, who has repeatedly called for Avandia’s withdrawal from the market, has been critical of FDA’s slow response. He will be a key scientist testifying at the FDA’s July 13 advisory committee meeting.
FDA in 2008 required GlaxoSmithKline to conduct a clinical trial directly comparing the safety of Avandia and Actos, but it has been slow to recruit patients and critics say it is unethical.
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