Was GlaxoSmithKline Worried About Avandia Risks?

Seattle, WAFor patients who take Avandia, learning about the risk of Avandia side effects may have come as a complete surprise before the strengthened warnings were added in 2007. However, reports have surfaced that GlaxoSmithKline, maker of Avandia, may have known about the risks before studies were released questioning the drug's safety.

An article in The Wall Street Journal (January 14, 2009) indicates that some GlaxoSmithKline consultants were concerned that the numbers in a study on Avandia were similar to their own, even as the company denounced the study's findings.

Specifically, a Glaxo senior consultant wrote in an email just before the study was published, "The numbers are the numbers, the analysis is very similar to our own." He went on to add that Glaxo could not "undermine" the numbers but could try to find a way to explain them.

The study in question was published in 2007 in the New England Journal of Medicine. That study, conducted by Dr. Steven Nissen, cardiologist at the Cleveland Clinic, found a 43 percent higher risk of cardiovascular events in patients who took Avandia. After the study was published, sales for Avandia dropped dramatically and congressional investigations into how the drug was marketed began.

Glaxo then released interim findings from its own study, called RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes, published July 5, 2007, in the New England Journal of Medicine). However, when the study was sent to the New England Journal of Medicine, the journal's editors requested some changes, according to The Wall Street Journal.

"The editors feel strongly that your data do not support the statement that the Record results for MI [myocardial infarction or heart attack] contradict the Nissen meta-analysis… This statement must be removed or modified," the editors reportedly wrote. Glaxo reportedly then revised the article to state that Avandia might be linked to higher cardiac risks but does not increase the risk of heart attack or death.

An editorial in the New England Journal of Medicine that appeared at the same time as the Record results, said the study "fails to provide exculpatory evidence" about Avandia and noted that too many participants left the study early. "The interim results of the RECORD trial do not provide any assurance of the safety of treatment with rosiglitazone [Avandia]," author wrote. He then pointed out that there are other drugs available that have longer and better safety records than Avandia.

In November, 2007, a black box warning was added to Avandia, warning about the increased risk of congestive heart failure.

Both the FDA and Glaxo have faced criticisms regarding their handling of Avandia, specifically, their failure to warn the public about the risk of cardiac events in patients who took the drug. Lawsuits have been filed against GlaxoSmithKline, alleging that patients who took Avandia were not warned about the increased risks associated with the diabetes drug.