Findings of "Disastrous" Avandia Study Kept Under Wraps by Drug MakerJul 13, 2010 | Parker Waichman LLP
The maker of Avandia had evidence about the drug’s heart risks as early as 1999, but concealed that information from U.S. regulators and the public. According to a new report in The New York Times, SmithKline Beecham, now GlaxoSmithKline, began a study that year to find out if Avandia was safer than Actos, a competing diabetes drug. The results of that study were disastrous for Avandia, the Times said.
That study, completed in 1999, showed Avandia held no benefit over Actos, and could be more dangerous to the heart. However, according to the Times, SmithKline Beecham did not post the results on its Web site or submit them to federal drug regulators, as is required in most cases by law.
“This was done for the U.S. business, way under the radar,” Dr. Martin I. Freed, a SmithKline executive, wrote in an e-mail message dated March 29, 2001, about the study results that was obtained by The Times. “Per Sr. Mgmt request, these data should not see the light of day to anyone outside of GSK.”
Avandia has been the subject of safety concerns for several years. In November 2007, a black box warning – the Food & Drug Administration’s (FDA) strongest safety warning – detailing Avandia’s association with myocardial ischemia was added to the drug’s labeling. The black box was added after the Cleveland Clinic published a meta- analysis of 42 clinical trails that showed patients taking Avandia had a 43-percent higher risk of having a heart attack.
Today, an FDA advisory panel is taking up Avandia, and will be asked to make a recommendation on whether or not it should stay on the market. Last week, we reported that in anticipation of that meeting, FDA staff had posted a 756-page briefing document to the agency’s Web site that is critical of the drug. One of the documents included in the posting is a memo highly critical of the so-called RECORD trial, another Avandia study paid for by GlaxoSmithKline. RECORD, which involved 4,500 patients, compared Avandia to patients receiving other diabetes drugs, metformin and sulfonylurea, for an average of 5.5 years. Released in 2009, RECORD did not show an increased heart-attack risk that has been seen in some other Avandia studies, and was used by Glaxo to tout its safety.
The memo included in the FDA briefing was written by Thomas Marciniak, a medical team leader in FDA’s division of cardiovascular and renal products. He writes that RECORD was “inadequately designed and conducted to provide any reassurance about the CV (cardiovasular safety) of rosiglitazone.” He goes on to write that the RECORD results “confirm and extend the recognized concerns regarding heart failure” and possibly suggest an increased risk for heart attacks.
According to today’s New York Times report, the FDA review of RECORD found at least a dozen instances in which patients taking Avandia suffered serious heart problems that were not counted in the trial’s tally of adverse events, mistakes that further obscured Avandia’s heart risks.