Thursday, September 13, 2007

More Bad News Coming on Avandia

By now everyone has seen the two newest studies on GlaxoSmithKline's diabetes drug (rosiglitazone) Avandia and Takeda Pharmaceutical's (pioglitazone) Actos in the Journal of the American Medical Association.

A study by Wake Forest researchers found that Avandia increased the risks of heart attack by 42% compared to control therapy, while another study by researchers at The Cleveland Clinic found that Actos lowered the risks of cardiovascular events, including heart attacks, strokes and death. You can read about it here.

Word on the street is there are more manuscripts to come. For example, results from a large (millions of patients), independent observational study comparing rosiglitazone to pioglitazone will be published soon, according to a source familiar with the manuscript, and the results won't be favorable for Avandia.

As you may recall, GlaxoSmithKline presented observational study data to support the case for Avandia during an FDA advisory committee meeting on July 30. GSK VP for Clinical Development Murray Stewart presented two large observational studies, one by Ingenix (2,095 heart attack events in over 400,000 patients) and one by PharMetrics Inc. (323 heart attack events in over 30,000 patients). The studies found no difference between Avandia and other antidiabetic agents for heart attacks, and there was no difference between Actos and Avandia, specifically.

It's unclear where and when the soon-to-be published observational study will show up, or even what study it is. But I'll go out on a limb here.

The most likely candidate is a California Medicaid study. At the end of his presentation at the Avandia advisory committee meeting, FDA Office of Surveillance & Epidemiology director for science and medicine David Graham cited a study he was co-authoring that looked at Type 2 diabetic Calfornia Medicaid patients. The study was not presented formally because it was incomplete.

Graham said at the meeting that out of roughly 2 million diabetic patients, there were a total of 6,000 hospitalized heart attacks. Avandia increased the relative risk of heart attack by 30% compared to control (statistically significant), while Actos did not increase the risk of heart attack (statistically significant).

“We found that rosiglitazone increased the risk the most. Sulfonylurea increased the risk next. Pioglitazone did not increase risk and metformin decreased risk,” he said.

So it doesn't look like things are going to get any easier for GlaxoSmithKline going forward. And that goes for FDA as well as the agency decides whether to withdraw Avandia from the market or leave it on pharmacy shelves with stronger warnings and possibly a risk management plan.

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