FDA panel's vote on Avandia reveals mixed opinions on diabetes drug's safety

By Rob Stein
Washington Post staff writer
Thursday, July 15, 2010

Federal advisers delivered a mixed verdict Wednesday on the diabetes drug Avandia, with a significant number of experts voting to recommend that it be pulled from the market because of safety concerns but a majority urging to keep it available, perhaps with tough new restrictions and new warnings.

The highly anticipated recommendations by the Food and Drug Administration advisory panel mark a crucial development in the long debate over Avandia, which was once the world's most popular diabetes drug but has become the focus of intense debate because of concerns that it increases the risk for heart attacks and strokes.

FDA Commissioner Margaret A. Hamburg will make the final decision about Avandia's future. Hamburg has pledged to make drug safety a priority, and many observers are watching what the agency does about Avandia as a potentially key moment for the FDA under the Obama administration. Agency scientists are divided about the drug's safety.

"Any action taken by the FDA after this vote, and after the agency's record with this drug, will be closely watched by physicians and patients who need to feel confident that the FDA has put science and safety first," said Sen. Charles E. Grassley (R-Iowa), who has been investigating Avandia.

In the most closely watched of a series of votes at the conclusion of an unusual two-day hearing, 12 of the 33 members of the FDA panel voted to withdraw Avandia. But 10 voted that it should remain available, with serious label revisions and possible restrictions on its sale. Seven voted to add further warnings to the drug's label. Three voted to continue to allow sales without any change in its status. One member abstained.

The votes came after the panel concluded that there was sufficient evidence to be concerned that Avandia increases the risk of heart attacks and strokes but insufficient evidence that the drug increases the risk of death.

The mixed vote illustrated the intensity of the debate over the drug. Critics, who were disappointed by the panel's vote, argued that the drug was clearly dangerous and unnecessary. Others expressed concern about pulling a drug that might be useful to some diabetics, who frequently need to try more than one medication.

The committee, which reviewed more than 1,000 pages of information and heard from 18 speakers who presented more than 500 slides of data, also voted to recommend that the FDA allow a large new international study by GlaxoSmithKline, the maker of Avandia, to proceed. The study is intended to help settle the issue by directly comparing the safety of Avandia with Actos, another popular diabetes drug. The study is controversial because of concerns that it would be unethical to give some patients a drug with known safety concerns.

Many panel members expressed frustration over the lack of clear evidence about the drug's safety or risks, especially given how long it has been used.

Approved in 1999, Avandia quickly became the world's most popular drug to treat Type 2 diabetes, the most common form of the disease and on the increase because of the obesity epidemic. But in 2007, Cleveland Clinic cardiologist Steven E. Nissen published a study concluding that the drug significantly increased the risk of cardiovascular problems, the leading cause of death among diabetics.

Sales of Avandia plummeted, and the FDA issued strong new warnings about the drug's safety. But after a panel of advisers voted later that year to keep the drug on the market, the FDA decided not to pull it, and hundreds of thousands of diabetics still use the drug.

Critics have argued that the decision to keep Avandia on the market illustrates the agency's failure to protect the public from dangerous drugs, especially in the wake of high-profile safety concerns about the painkiller Vioxx and other medications.

Since then, more evidence has accumulated about the drug's risks, as well as allegations that GlaxoSmithKline knew about the dangers but hid them from regulators and the public. The company has denied the charges and has defended the drug's safety.

"We will, of course, continue to work with the FDA in the best interest of diabetes patients who face this chronic and serious disease," GlaxoSmithKline's Ellen Strahlman said in a statement. "Patients taking Avandia should speak with their physician about their treatment and any questions they may have regarding the safety of the medicine."

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