The blockbuster diabetes drug Avandia is likely to be sold in a strikingly different way, even if the U.S. Food and Drug Administration chooses to keep it on the market, as a majority of expert panelists have recommended.
The FDA advisory panel voted 20-12 today to recommend keeping the controversial treatment on the market but 17 voted in favor of stricter warning labels or restrictions on its sale. Only three voted not to change the existing warning.
One member abstained from voting. No member voted to take the current warning label off the box.
The culminating vote came after a majority of panel members thought analyses of previous studies persuaded them the drug was linked to significant heart risk in diabetes patients and that its market competitor, Actos, showed to be a stronger alternative.
Based on the panel's recommendations, it is likely the drug will face more restrictions on labeling and marketing.
"Today, the risk clearly outweighs the benefits in Rosi [Avandia]," panel member Dr. Curt Furberg said. "The benefit is modest at best."
The 33-member panel voted on nine questions, one of which addressed whether the drug should be pulled from the market in light of ongoing analyses suggesting that Avandia could worsen certain risk factors for heart disease.
The panel found that the data presented was sufficient to raise significant safety concerns for heart risk in patients with Type 2 diabetes compared to other diabetes treatments, including market competitor Actos. The panel also voted 20 to 12 that researchers continue the TIDE trial, a study that is comparing Avandia to Actos.
"I think the totality of evidence is much stronger -- it's still not absolute -- but it's stronger [than 2007]," panel member Dr. Clifford Rosen said.
Some panel members said they found no clarity in either the safety or risk of Avandia in the past two days than when Avandia's safety was initially called into question in 2007.
"This drug is not for everybody but that may be that it's not for anybody," panel member Rebecca Killion said today during discussions prior to voting.
Some members said studies on Avandia made it difficult to tell whether the data was accurate enough to predict that the drug may be linked to stroke, heart attack and even death in some patients. The studies reviewed by the panel included an evaluation of many studies, known as a meta-analysis, along with observational studies; two study designs that some members thought were insufficient to show serious risk with the drug.
"I think if you have a lot of short-term trials, you don't have a lot of deaths," Geller said. "Overall, I think the evidence is missing."
Indeed, the majority voted that the data presented on Avandia was insufficient to raise safety concerns for death in diabetic patients compared to other treatments. And a majority of members were unable to conclude whether patients who took Avandia have a higher risk of death compared to those who took Actos.
"There's absence of evidence but I want to emphasize that doesn't mean there's evidence of absence," said panel member Dr. Thomas Flemming, who voted that the data makes it unclear whether Avandia contributes to a higher risk of death.
As with others, Flemming recommended longer-term studies to more accurately understand the risks and benefits of the drug.