According to Wolfe's prepared testimony, FDA adverse-reaction
reports filed since Avandia hit the market in 1999 have shown the
drug had a 15.2 times higher adjusted rate of
"There is no evidence of any uniquely beneficial clinical outcome for Avandia and growing evidence of unique risks in multiple organ systems," Wolfe said. "If Avandia were up for approval today, based on what is now known, it would be summarily rejected. There should not be a double standard for removing it from the market."
For its part, Avandia's maker, GlaxoSmithKline, insisted before the meeting that the drug does not increase the risk of heart attack. "We don't believe that a warning about heart attack should be on the label," said Dr. Andy Zambanini, director of clinical development at GlaxoSmithKline.
"Avandia is one of the most studied medicines in the diabetes field," Zambanini said. "We have looked at all the available data both from short-term trials, long-term trials and real-world data, in terms of epidemiology. There is really no evidence of an increase in cardiovascular death with Avandia. And when you look at Avandia and compare it with all the other similar agents, there really is no difference in heart attack risk."
One of the studies that GlaxoSmithKline is relying on to make its case is the RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes) trial. The study, sponsored by Glaxo, was specifically designed to determine the risks for heart attack from Avandia.
Dr. David Graham, associate director for science and medicine in the FDA's Office of Surveillance and Epidemiology and an Avandia critic, disagreed with Glaxo's interpretation of the RECORD study. In a report submitted by the FDA to the advisory panel before the hearing, Graham concluded:
"RECORD does not now, nor will it at completion, provide
meaningful evidence to demonstrate with any degree of certainty
that RSG [Avandia] does not increase the risk of
