1 Boring Old Man

GlaxoSmithKline Knew of Avandia’s Cardiac Risks, Senate Report Says
Wall Sreet Journal
By JARED A. FAVOLE And ALICIA MUNDY
February 20, 2010

WASHINGTON—Confidential studies by Food and Drug Administration officials recommend that GlaxoSmithKline’s Avandia, a diabetes medicine, get pulled from the market because it is linked to heart attacks. The studies, released as part of a report on Avandia by staff of Senate Finance Committee members Chuck Grassley (R., Iowa) and Max Baucus (D., Mont.), also say any head-to-head trial where patients get Avandia and Takeda Pharmaceutical Co.’s diabetes medicine Actos would be "unethical and exploitative." GlaxoSmithKline is currently sponsoring a study, called TIDE, where patients get either Avandia, Actos or other medicines.

GlaxoSmithKline said in a prepared statement that it has extensively studied Avandia in more than 52,000 patients and none of its reports shows a statistically significant association between Avandia and heart attacks. The company said the TIDE study was mandated by the FDA and "has been approved by an independent review board and appropriate safety boards that are responsible for assessing the safety of conducting the trial." The company also noted that an FDA-convened advisory committee of scientists and doctors in 2007 voted in favor of keeping the medicine on the market. The news of the Senate Finance Committee report and internal FDA studies were first published by The New York Times on Saturday. That panel voted 22 to 1 to keep the drug available but also voted 20 to 3 that Avandia increases the risk of a heart attack.

The dust-up over Avandia started in 2007 when Cleveland Clinic cardiologist Steve Nissen published a study in the New England Journal of Medicine that found a 43% higher risk of cardiovascular events for patients taking Avandia. Glaxo publicly denounced the findings, but internal emails since released and included as part of the Senate Finance Committee report indicate that company scientists felt the company’s own numbers were similar to Dr. Nissen’s. The company has faced criticism that it has known about the heart-attack risks associated with Avandia for years. Glaxo added a "black box" warning to Avandia in November 2007 that says the drug can cause or exacerbate congestive heart failure…

The Senate Finance Committee report concludes that Glaxo was aware of the possible cardiac risk years prior to Dr. Nissen’s study. The report says Glaxo had a duty to warn patients and the FDA about its concerns in a timely manner. "Instead, GSK executives intimidated independent physicians, focused on strategies to minimize findings that Avandia may increase cardiovascular risk, and sought ways to downplay findings that the rival drug ACTOS (pioglitazone) might reduce cardiovascular risk," the report says.

• 20 Feb 2010: GSK rejects conclusions of Senate Committee on Finance Staff Report on Avandia
• 20 Feb 2010: GSK rejects conclusions reported in The New York Times story on Avandia
• 5 June 2009 – Large, long-term study shows Avandia has no increased overall cardiovascular risk compared to other commonly used diabetes medicines