Thursday, October 02, 2008

Obesity Drugs: Another One Bites the Dust

From time to time here at the IN VIVO Blog, we write about something not because it’s a clever deal, or a shocking policy out of Washington, or an interesting industry trend that we think you should be aware of—but simply because we were right.

This is one of those times.

Merck has decided to discontinue development of taranabant, its cannabinoid-1 receptor blocker in Phase III development for obesity. Why? Well, in short, the only doses that were effective in weight management also had an unacceptable level of psychiatric adverse events.

Indeed, Merck had already dropped the two high doses of taranabant in clinical studies (4 mg and 6 mg) due to statistically significant differences in crying, mood swings, anxiety and depression. At the lowest dose (2 mg), patients reported the same adverse events, although the results were not statistically significant.

The problem was that the efficacy at that low dose wasn’t terribly impressive. Among those patients, 57% lost 5% of their body weight and 28% lost 10% of their body weight. That sounds nice, but when you consider that these are obese patients with a body mass index of at least 30 kg/m2, it’s really not that much to lose—especially in light of the psychiatric adverse event trend.

Given that taranabant is in the same class of drugs as Sanofi-Aventis’ rimonabant (once Acomplia, later Zimulti), and had pretty much the same profile, we saw this one coming. We probably weren’t alone in that thinking, but we’ll continue with the shameless self-promotion anyway—click here for that story in The RPM Report.

But we also have to applaud Merck for having the courage to put a dead drug down—instead of being so blinded by dollar signs as to fail to see that there’s no chance for FDA approval until deep into the drug review process. Of course, when you bank much of a future franchise on a single product, it can be hard to see the forest through the trees.

The taranabant failure happened despite—or perhaps because?—Merck hired two prominent FDA officials that could offer advice on the application: Robert Meyer, the FDA division director that was in charge of reviewing taranabant, and Peter Honig, who was a prominent drug safety official in his days at the agency.

Perhaps it was that expertise that helped convince Merck of the bigger picture. FDA isn't going to approve a relatively ineffective drug that has that kind of a safety signal—especially given the agency's recent crackdown on drugs with psychiatric adverse events.

Or maybe Merck knew that already. Regardless, one thing is clear: like so many others before it, cannabinoid-1 receptor blockers are proving to be a tough drug class. Taranabant is just the latest drug to fall.

1 comment:

Anonymous said...

The real mystery here is why Merck leadership (or that of any other pharma, for that matter) spent even a single day developing a medicine that modulates the CB-1 receptor.
The marijuana receptor? Really? Unacceptable and unpredictable psychotropic side effects, occurring infrequently enough that they would never be detectable in efficacy and safety testing in animals, or early clinical trials in small numbers of humans? Just what did they expect?
It is said that Big Pharma has recently "happened" upon hard times. Leadership blythely cites the general difficulty of new drug development. It appears more appropriate to say that Big Pharma has brought hard times upon itself through ill-informed decision making at the highest levels.
Sounds like Jimmy Cayne, Dick Fuld, and Stan O'Neil in a different industry to me.