FDA Issues Approvable for Acomplia for Weight Loss; Not Approvable for Smoking Cessation
And yet another surprise on the metabolic therapeutics front this week. Acomplia (rimonabant) was issued an approvable letter from the FDA yesterday, rather than an outright approval, for rimonabant, the pioneer in the CB1 antagonist (inverse agonist) class for obesity. They received a non-approvable for smoking cessation. Many observers believed that Sanofi-Aventis would gain approval for obesity on the first go-around, myself included, although at least one Wall Street analyst, Tim Anderson of Prudential, was cautious in his optimism, giving a first-round approval probability of under 50%. It’s a major setback for the company, which will now face an unknown delay in the first launch of Acomplia, as they prepare to answer FDA’s objections to approval.
So, what were the issues that gave FDA pause? The company isn’t saying. Here are some possibilities: (1) Manufacturing quality: FDA has used this issue to delay approval of a number of major’s recent products recently, but S-A hasn’t had any recent manufacturing problems made public. (2) Preclinical safety/tox: I highly doubt this is an issue. Much of the preclinical data on rimonabant has been published and looks okay. (3) Clinical safety: Might be playing a role; some issues with depression arose in the clinical trials. But the obesity safety database was large and long enough, and S-A did a reasonably good job investigating the psych issues already. (4) Clinical efficacy: The drug works to aid weight loss. It’s not great, but it’s as good as the other stuff that’s already being sold. That said, there were a large number of dropouts in the Phase 3 obesity program, and that might have given FDA pause, depending on what secondary efficacy analyses showed. But I don’t think so. (5) Label impasse: This has my vote for likeliest reason for a delayed approval. I’m betting that S-A initially tried for a kakameyme indication that included the “metabolic syndrome,” an embattled classification for the grouping of common cardiovascular risk factors thought to be causally related to insulin resistance. My opinion comes from statements S-A’s Doug Greene, clinical leader of the Acomplia program, and other S-A executives have made previously. You see, S-A wants obesity-related complications in its label to get the support from third-party payers it needs to make Acomplia a blockbuster. They might have determined that it wasn’t worth launching the drug with only the uncomplicated obesity claim without having at least one complication claimed–the more complications claimed the better, and the metabolic syndrome best of all. If FDA believes that data supporting a lipid or diabetes complication claim are lacking (I don’t know why they would), S-A might elect to perform an additional clinical trial before re-submitting an NDA. This could mean a delay in US approval of up to two years. If, on the other hand, if this approvable action is the result of S-A deciding that they wanted it all or nothing at all in their label, then they rightly deserve to be severely punished by investors.
February 15th, 2007 at 12:33 pm
[...] Following FDA’s non-approvable decision for rimonabant (Acomplia) last year, I referred to Sanofi-Aventis’ pursuit of an indication for the metabolic syndrome as “kakameyme”. Seems like FDA’s Metabolic and Endocrine Division (DMEDP) agrees with me. [...]