More Damning News about Avandia One Month before FDA Review

Washington, DCA well-known and outspoken reviewer for the US Food and Drug Administration (FDA) has released study data suggesting that type 2 diabetes drug Avandia increases the risk of heart attack by 25 percent, the risk of stroke by 27 percent and the risk of death by as much as 17 percent when compared with rival diabetes drug Actos, manufactured by Takeda Pharmaceuticals.

Dr. David Graham, who famously blew the whistle on Vioxx and led the charge to remove it from the market, wants nothing less for Avandia.

In an email to FDA Commissioner Margaret Hamburg dated May 28—correspondence that has been confirmed by FDA officials, according to Reuters—Graham presented the findings of an observational study based on data from 230,000 Medicare patients.

Graham and his colleagues found that in the 10-year period spanning from 1999 to June 2009 there were 48,000 excess complications with Avandia use in older patients. Due to the fact that Medicare patients are 65 years of age or older, a demographic that accounts for less than 40 percent of total Avandia users, "the national impact is probably 100,000 or more," Dr. Graham wrote.

A copy of his email was obtained by Reuters and confirmed by the agency.

The findings add additional fuel to the smoldering fire under Avandia, whose manufacturer—GlaxoSmithKline (Glaxo)—has seen sales drop by more than half since a 2007 Cleveland Clinic study suggested that Avandia use results in a greater risk for heart attack and stroke.

Graham has requested that the Journal of the American Medical Association publish his findings.

For its part, Glaxo told Reuters in an email communiqué on June 11 that it would be premature to comment on Graham's study until the findings have been peer-reviewed.

"However, it is important to note that there are inherent limitations with retrospective observational studies, including variables that were not considered nor corrected for when conducting the study, which can significantly impact the validity of the data," the company said.

Next month the FDA will convene an advisory panel to debate the merits of Avandia. According to Reuters, options include imposing further restrictions on the drug, leaving it alone or pulling it from the market altogether.

Dr. Graham pushed for the latter response three years ago when he appeared before an FDA advisory panel and advised that Avandia be pulled from pharmacy shelves. At that meeting, according to the Reuters' report, the panel voted 22-1 in favor of keeping Avandia on the market.

The latest study was undertaken by Graham and his various colleagues at the FDA, as well as colleagues at the Centers for Medicare and Medicaid Services. The FDA subsequently reviewed his findings and the agency has given him permission to submit the study for peer review and publication, so long as he made it clear that the findings were not those of the FDA.

A spokesperson at the agency verified to Reuters that Graham's findings would be included on the roster for presentation to the FDA advisory panel on Avandia side effects in July.