FDA Orders New Safety Labels for Roseglitazone (Avandia) and Pioglitazone (Actos)

WASHINGTON, June 6 -- FDA Commissioner Andrew C. von Eschenbach, M.D., told a congressional hearing today that the FDA will beef up the cardiovascular warnings on the labels of both rosiglitazone (Avandia) and pioglitazone (Actos).

Moreover, the FDA announced it will convene a safety panel on June 30 to review the cardiovascular risks of roseglitazone.

Rep. Henry Waxman (D-Calif.) convened the hearing to investigate the FDA's handling of rosiglitazone from its approval in 1999 through recent reports that linked the drug to increased risk of cardiovascular events.

In general, Dr. von Eschenbach defended the FDA's handling of rosiglitazone, but he conceded that the agency asked for the label changes on May 23-two days after the New England Journal of Medicine published a meta-analysis that found a 43% increase in risk of myocardial infarction among patients taking rosiglitazone.

The lead author of that analysis -- Steven E. Nissen, M.D., chairman of cardiovascular medicine at the Cleveland Clinic -- was aggressively questioned by Republican members of the committee who accused Dr. Nissen of sensationalizing what they characterized as questionable findings.

The Republicans also grilled Dr. Nissen over his decision to share his concerns about the safety of rosiglitazone with Waxman in February.

Rep. Darrell E. Issa (R-Calif.) was prosecutorial as he repeatedly attempted to limit Dr. Nissen to "yes" or "no" answers. Issa said that if Dr. Nissen had safety concerns about the drug, he should have taken those concerns to the FDA, not to committee staff appointed by Democrats.

Several times Issa and other Republicans pressed Dr. Nissen about whether he had shared his findings with Democrats on the committee before the meta-analysis was published.

Dr. Nissen repeatedly stated that his interest in rosiglitazone was purely that of a physician-scientist, whose goal was to disseminate information to both physicians and patients.

John Buse, M.D., of the University of North Carolina and president-elect of the American Diabetes Association, testified that he received threatening phone calls when he questioned rosiglitazone's cardiovascular safety in 1999. He said his department chairman was also approached by the drug's maker -- then Smith Beachum now GlaxoSmithKline.

He said that twice representatives of the drug company accused him of being a liar and "for sale" and raised the possibility of a billion libel suit. Dr. Buse said the situation was finally resolved when he agreed to sign what he characterized as a sort of cease-and-dissent letter. In the letter Dr. Buse agreed to back off his criticism and in turn asked the company to "call off the dogs."

Moncef Slaoui, Ph.D., chairman of research and development for GlaxoSmithKline, presented the company's cas,e testifying that rosiglitazone had demonstrated superiority over two diabetes drugs -- metformin and sulfynurea -- and that the company has gone out of its way to confirm the safety of rosiglitazone.

Dr. Slaoui testified that the interim results from the RECORD trial, published online yesterday by the New England Journal of Medicine, provided reassuring data about the drug's safety. The study did not find a significant increase in MIs, but found a significant increase in heart failure. But three accompanying editorials pointed out that although the data did not confirm the risk found in the earlier meta-analysis, neither did they refute that finding.

Dr. Slaoui said he was "extremely disappointed" with the three editorials.