FDA panel says Avandia should stay, but with restrictions

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Faced with conflicting and less-than-conclusive scientific evidence, a Food and Drug Administration advisory panel recommended Wednesday that the controversial diabetes drug Avandia remain on the market — but with tighter supervision and increased warnings about the danger of heart attacks.

Advisory recommendations are not binding and the FDA is expected to take at least several weeks to consider its response, but the panel’s expression of increased concern is likely to further reduce doctors’ reliance on what was once the drug of choice for treating Type II diabetes.

Reflecting the difficulty of balancing potential risks and benefits for individual patients, 10 members of the 33-member panel voted to keep Avandia on the market under close supervision, seven voted to permit continued marketing but with stronger label warnings, and three favored the status quo. One member abstained. Twelve members voted to remove the drug from the market.

Several panelists said they were persuaded to vote in favor of limiting or eliminating Avandia because another drug, Actos, works as well but has not shown as many side effects.

The votes by a majority of the committee’s members essentially affirmed a recommendation by a similar panel in 2007 that concluded Avandia could increase the risk of heart attacks but nonetheless should remain on the market.

Also known as rosiglitazone, Avandia is used to control blood sugar by making the body more sensitive to insulin. Unlike patients with Type I, or juvenile diabetes, patients with Type II continue to produce insulin, but their bodies do not use it effectively.

Reliance on Avandia has dropped sharply in recent years as evidence began to accumulate linking it to increased risk of heart attack.

At the peak of its popularity in 2006, 13 million prescriptions were written, according to IMS Health, a pharmaceutical market research company. By 2009, the number had declined to about 2.6 million, the firm said. GlaxoSmithKline, the drug’s maker, said about 550,000 Americans took medications containing Avandia in the last year.

Dr. Jacob Warman, chief of endocrinology at the Brooklyn Hospital Center in New York, said he expected use of the drug to drop further.

“There is so much negative press that lay people are going to say, ‘Why are you giving that to me? Why don’t you give me the other drug?’ Doctors are not going to fight the patients,” he said.

“It’s not officially dead in the water, but practically speaking, it should be,” he added.

But opinions among diabetes specialists were divided.

The FDA’s decision was “probably very appropriate,” said Dr. Robert Greenfield, a cardiologist at MemorialCare Heart & Vascular Institute at Orange Coast Memorial Medical Center in Fountain Valley. “When you use Avandia … in the proper patients, you can get very good results,” particularly in those with high cholesterol, he said.

“For a relatively young diabetic patient that needs additional control, it is a very reasonable medication,” Greenfield said. “For an older patient with complications, maybe it is not such a good choice.

“I’m happy that we will continue to have it as a tool in our toolbox to use in appropriate cases,” he said.

Several members of the FDA’s advisory panel expressed frustration at the lack of clear-cut data despite 18 presentations, about 500 slides and 1,000 pages of background material laid before the committee in the course of its two-day hearing.

“We’ve seen enough ambiguity to last a lifetime,” said Dr. Sanjay Kaul, a cardiovascular specialist at Cedars-Sinai Heart Institute.

Dr. Clifford Rosen of the Maine Medical Center Research Institute said: “The totality of evidence is now stronger. It’s not absolute, but it’s stronger” that Avandia is a problem.

Cleveland Clinic cardiologist Dr. Steven Nissen, whose 2007 analysis of several Avandia studies touched off much of the controversy over the drug, said after the panel’s vote, “They gave the leadership of FDA enough ammunition to withdraw the drug if they want to withdraw it.”

Nissen’s review found that the drug increased the risk of heart attack by roughly a third compared with recipients of other medications or a placebo.

Last month, an updated analysis by Nissen published in the Archives of Internal Medicine confirmed that finding.

Yet another report, a study of Medicare patients overseen by FDA researcher David Graham and published in the Journal of the American Medical Assn., found that Avandia boosted the chance of stroke by 27% and heart failure by 25% compared with Actos, made by Takeda Pharmaceuticals North America.

But GlaxoSmithKline pointed to other studies that it said showed that rates of cardiovascular events were comparable between Avandia users and people taking other diabetes medicines.

And a study released last month at an American Diabetes Assn. meeting concluded that Avandia did not trigger cardiovascular events more than other diabetes medications.

Zajac reported from Washington and Maugh from Los Angeles.