FDA panel: Diabetes drug should stay on market

WASHINGTON (AP) - GlaxoSmithKline's drug Avandia should stay on the market, federal health experts voted Wednesday, but the controversial diabetes pill should be subject to new restrictions due to risky heart side effects.

A panel of Food and Drug Administration advisers voted 20-12 to keep the once blockbuster pill available for diabetics. But 10 panelists also called for limiting who can receive and prescribe the much-debated medication.

The vote marks a tough win for British drugmaker Glaxo, which is facing thousands of lawsuits from patients who say Avandia caused their heart attacks or strokes. While the company may fare better in court due to the panel ruling, sales of Avandia are likely to shrink to minuscule levels.

The FDA is not required to follow the advice of its panelists, though it usually does. FDA officials said they would review the recommendations and make a decision on Avandia as soon as possible.

The vote came despite an earlier ruling by the panel that Avandia appears to increase heart attack risk, underscoring the often contradictory evidence for and against the drug.

Panelists voted 21-4 that Avandia is more likely to cause heart attack than its closest competitor Actos. Eight panelists said there was not enough information to make a decision.

Ultimately though, panelists said the risks were not severe enough to justify removing a drug used by hundreds of thousands of patients.

"I didn't want to take away a drug without definitive evidence that it was bad for those few patients who need it," said University of Missouri Lamont Weide, who voted to leave the drug on the market with new restrictions.

The agency convened the two-day panel meeting to help untangle over 1,000 pages of conflicting evidence about Avandia's risks.

The drug has a long, knotty history at the FDA.

Since diabetics are already predisposed to heart risks it is extremely difficult to tell which heart attacks are drug-related and which are simply caused by the disease.

The task of evaluating Avandia's possible side effects across dozens of studies has dragged on for years without definitive answers.

Three years ago a similar FDA panel voted to keep Avandia on the market and the FDA responded by adding bolder warning labels for the drug.

"In terms of what has changed since 2007, I think the totality of evidence is much stronger," said panelist Clifford Rosen of the Maine Medical Research Institute. "It's still not absolute but it's stronger."

Despite the vote on Avandia's heart risks, panelists didn't reach a firm conclusion on whether it is more likely to cause death than other drugs.

The panel vote to keep Avandia on the market would appear to support FDA leadership, who have been criticized by some members of Congress for not pulling the drug.

But late Wednesday those critics were already questioning the legitimacy of the meeting.

"The result of the advisory committee vote is gravely disappointing and raises serious questions as to whether the science was presented in an unbiased manner," said Congresswoman Rosa DeLauro, D-Conn., who has called for Avandia's withdrawal.

Panelists sat through nearly 20 presentations on Avandia that often drew opposite conclusions.

FDA reviewer David Graham told the panel Avandia's risks were real enough "to put you in a hospital or a cemetery."

Graham, who wants the pill banned, recently published an analysis estimating that as many as 100,000 heart-related problems may have been caused by Avandia among seniors on Medicare.

But higher ranking FDA officials played down the drug's risks, pointing out that clinical trials have not shown increased risk of heart attack or death with Avandia. Considered the gold standard of medical research, clinical trials randomly assign patients to receive one of two drugs and follow them to see how they fare.

Minutes before the final vote on Avandia, John Jenkins, the FDA's director for new drugs, emphasized the high bar needed to pull a previously approved drug from the market.

"The two that have been withdrawn for cardiovascular concerns - Vioxx and Zelnorm - showed three, four or five fold-increase in risk," Jenkins said.

Panelists appeared to heed the cautionary tone.

"I would be concerned about the precedent that would be set to have this quality of data sufficient to remove a drug," said John Teerlink of the University of San Francisco.

The FDA first approved Avandia in 1999 and it quickly became the top-selling diabetes pill in the world. U.S. sales have plummeted from $2.2 billion in 2006 to $520 million last year as safety concerns swirled around the drug.

The drug works by increasing the body's sensitivity to insulin, a key protein needed for digestion that diabetics don't adequately produce.

While there are more than a dozen diabetes drugs on the market, only Actos from Japan-based Takeda Pharmaceuticals works the same way as Avandia. U.S sales of Actos have risen steadily - hitting $3.4 billion last year - as Avandia's reputation has soured.

Critics of Avandia say there is no reason to leave the drug on the market when Actos provides the same benefits without the potential heart risks.

FDA is requiring GlaxoSmithKline to conduct a definitive study comparing the safety of the two drugs, but patient enrollment has slowed to a crawl due to Avandia's negative reputation.

The FDA panel said the study should go forward, though results will not be available for at least five years.