A report from the Senate Finance Committee released yesterday suggests that GlaxoSmithKline may have known for some time that Avandia could cause heart trouble--but didn't tell anyone about it.
The drugmaker should have warned patients and the FDA about its concerns, but instead "intimidated independent physicians, focused on strategies to minimize findings that rosiglitazone may increase cardiovascular risk, and sought ways to downplay findings that the rival drug ACTOS (pioglitazone) might reduce cardiovascular risk," the senators wrote in a letter to FDA Commissioner Margaret Hamburg.
The report (viewable here) suggests that GSK may have known about Avandia's heart risks well before a 2007 study which found Avandia patients have a higher risk of dying from heart problems. It also contains a study conducted by FDA reviewers David Graham and Kate Gelperin, which found Avandia is linked to 500 more heart attacks and 300 more heart failures than its main competitor. In no uncertain terms, they recommend that Avandia be yanked from the market.
Even without FDA action, doctors aren't touching Avandia with a ten-foot pole. According to ABC News, an overwhelming majority of doctors it interviewed say they no longer prescribe it.
The NYT reported on Saturday that GSK's own studies into Avandia may be fraught with risks.
Dr. Graham and Dr. Gelperin, working in the F.D.A.’s office of surveillance and epidemiology, argued in two separate internal reports that the new GlaxoSmithKline study, called TIDE, is "unethical and exploitative" because patients given Avandia face far greater risks than those given Actos, with no promise of any additional benefit. The trial may include patients who have had heart attacks or chest pains even though some foreign drug authorities have warned against Avandia’s use by precisely such patients, the reports note.
"Although the proposed TIDE trial is motivated by a desire for definitive answers regarding the cardiovascular safety of the drug rosiglitazone, the safety of the study itself cannot be assured and is not acceptable," one of the reports concludes.
Graham and Gelperin had expressed their concerns as early as 2008, in part due to studies that suggested Actos controlled blood sugar as well as Avandia without as much risk to the heart.
If it is indeed true that GSK knew about the heart risks of Avandia and didn't tell anyone, it's yet another chapter in the recent disgraceful history of drug safety.