July 15, 2010

Avandia To Remain On The Market

A panel of U.S. Food and Drug Administration advisers voted Wednesday to allow GlaxoSmithKline's diabetes drug Avandia to remain on the market, but with new restrictions due to the risky cardiovascular side effects of the controversial pill.

The panel of experts voted 20-12 to retain availability of Avandia to diabetics, although 10 panelists called for limiting who can receive and prescribe the once-blockbuster medication.

British drugmaker Glaxo has been hit with thousands of lawsuits from patients who claim Avandia is responsible for their strokes or heart attacks.  And while the panel's ruling may help the company in court, sales of Avandia, used by hundreds of thousands of patients, are likely to suffer significantly.

Officials with the FDA said they would review the panel's recommendations and make a final decision on Avandia as soon as possible.  The agency is not required to follow the advice of its panelists, but typically does.

Wednesday's vote follows a previous 21-4 ruling by the panel that Avandia is more likely to cause a heart attack than the drug's closest rival, Actos --further highlighting the contradictory evidence for and against the drug. 

Ultimately, the panelists said Wednesday that the risks of Avandia were not severe enough to warrant the drug's removal from the market.  

"I didn't want to take away a drug without definitive evidence that it was bad for those few patients who need it," the Associated Press quoted panelist Lamont Weide of the University of Missouri as saying.

Weide voted in favor of keeping Avandia on the market with new restrictions.

The FDA convened the two-day panel meeting to examine over 1,000 pages of conflicting evidence about the side effects of Avandia, which has had a contentious history at the agency.

Since diabetics are already predisposed to heart risks, it is often difficult to determine which heart attacks are drug-related and which are merely a result of the patient's diabetes. 

Evaluation of Avandia's possible side effects across scores of studies has continued for years without conclusive answers. 

A similar FDA panel voted three years ago to keep Avandia on the market, and the agency responded with bolder warning labels for the drug.

"In terms of what has changed since 2007, I think the totality of evidence is much stronger," panelist Clifford Rosen of the Maine Medical Research Institute told the Associated Press.

"It's still not absolute but it's stronger."

Despite the panel's vote, it did not reach a firm conclusion on whether Avandia is more likely to cause death than other medications.

The vote also seems to support FDA leadership, who have been criticized by some lawmakers for not pulling the drug from the market.  Indeed, members of Congress were already questioning the panel meeting's legitimacy late Wednesday.

"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-CT), who has called for Avandia's withdrawal.

Panelists sat through nearly 20 presentations on Avandia, some of which drew opposite conclusions.

Addressing the panel, FDA reviewer David Graham, who wants the drug banned, said Avandia's risks were serious enough "to put you in a hospital or a cemetery."

Graham recently published a report estimating that Avandia may be responsible for up to 100,000 heart-related problems among seniors on Medicare.

However, higher-ranking FDA officials downplayed the risks, citing clinical trials that have failed to demonstrate an increased risk of heart attack or death with Avandia.  Clinical trials, long considered the gold standard of medical research, are studies that randomly assign patients to receive one of two drugs, and then follow participants to track their progress.

Minutes before the panel's final vote, John Jenkins, the FDA's director for new drugs, stressed the high threshold required 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," he said.

The panelists seemed to heed Jenkins' advice.

"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.

Avandia first gained FDA approval in 1999, and rapidly rose to become the world's top-selling diabetes pill.   But U.S. sales of the drug have plunged from $2.2 billion in 2006 to $520 million last year amid safety concerns.

Avandia works by increasing the body's insulin sensitivity.  Insulin is a critical digestion protein that diabetics do not produce in adequate amount.

Although there are many diabetes drugs on the market, only Actos works in the same way as Avandia.  Avandia's critics say there is no reason the drug should remain on the market when Actos provides the same benefits without the potential risks.

U.S sales of Actos, made by Japan-based Takeda Pharmaceuticals, have risen steadily to $3.4 billion last year amid safety concerns surrounding Avandia.

The FDA is requiring GlaxoSmithKline to conduct a definitive study comparing the safety of Avandia and Actos, but patient enrollment has been sparse due to Avandia's reputation. The FDA panel recommended that the study go forward, although results will not be available for at least five years.


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