Judgment Day has finally arrived for GSK’s Avandia. FDA’s Endocrinologic and Metabolic Drugs and Drug Safety and Risk Management Advisory Committees met July 13 and 14 to finally recommend, after months of deck-stacking against GSK, that the drug be severely restricted, if not outright pulled from the market. In the vote, 12 of 33 panelists said it should be removed in the US, and of the 10 who voted for the slightly less extreme action of additional label warnings and prescriber restriction—possibly limiting it to a second-line treatment—several said they were leaning toward removal, but were dissuaded by some of the bad study data.
The majority of the panel found there was a greater risk of major adverse cardiovascular events (heart attacks, strokes, etc.) for patients taking Avandia than those taking other diabetes drugs. (It didn’t find an increase in mortality, however.)
During the meeting, GSK trotted out details from its RECORD study that supported its hypothesis that Avandia benefits Type 2 diabetes patients in the long run and does not cause an increase in risk.
The company also released a statement July 13 echoing what it had told the Senate Finance Committee and FDA months before: Avandia critics are cherry-picking documents that support their claims of increased risk of adverse cardiovascular events; furthermore, comparisons that favor Takeda’s rival diabetes drug Actos are invalid, since one of the studies did not compare the performance of the two drugs in regards to cardiovascular events.
The “trial” itself played like a game of statistics ping-pong, with different analyses and accusations of data manipulation batted around by both sides. The sheer number of trial design flaws worked in both parties’ favors, and the debate over which studies should be included in decision-influencing meta-analyses raged throughout both days.
But much of the damage to GSK’s case had already been done before the meeting: Reports of study coverups (in The New York Times, no less) and paper ghostwriting have been plaguing the company for months. And the company announced on Tuesday it would settle around 10,000 suits for a total of $460 million. The suits alleged the very problems Avandia critics have vocalized over the last several years.
One of the reviewers to recently join the critics was Thomas Marciniak, who blasted GSK’s lynchpin RECORD trial for not only being poorly designed, but also poorly executed. Marciniak found numerous instances of ignored or severely delayed reporting of cardiac events in Avandia patients. He also argued, in his slides, that he has no bias, as “neither [his] job nor (for [him]) hundreds of millions of dollars are riding on the results.” And, far from GSK’s claim that RECORD vindicates its drug, Marciniak said he found that the study does suggest Avandia increases the risk for heart attack.
FDA doesn’t have to follow the panel’s recommendation. But the agency’s ultimate decision on Avandia’s fate will be indicative of the direction commissioner Margaret Hamburg’s regime is taking: Will it lean towards getting—and keeping—as many drugs into the market as possible, or will it take the safer route of risk management?