Rimonabant Bites the Dust

For several years now, rimonabant (Acomplia, by Sanofi-Aventis) has been touted as the next pharmaceutical blockbuster. Several well-conducted clinical trials showed that rimonabant produced significant weight loss, aided in smoking cessation, and improved the cardiac risk profile of patients who took it. Reports in the news, replete with quotes by "leading doctors," called rimonabant a true breakthrough that would revolutionize the management of obesity and smoking.

One of the few to sound a cautionary note was yours truly, who pointed out in 2006 that once this drug was released out into the wild, it would be immediately prescribed to hundreds of thousands of enthusiastic patients - and any lurking "low incidence" side effects that remain undetected would suddenly manifest. I urged caution among doctors, patients, and the drug company in introducing this drug to the marketplace.

The FDA agreed with that caution. While rimonabant was approved in many countries, the FDA subsequently held up the drug pending more studies - so it was never approved in the United States.

With wider use of the drug around the world, a disturbing side effect was noted - psychological problems and suicidal tendencies. Two weeks ago, the European regulatory agency asked the company to suspend marketing of the drug while this problem was studied further. And this week, Sanofi-Aventis halted ongoing research trials with rimonabant, strongly signaling that the drug is for all purposes finished.

If it is any consolation to those who have been waiting for a weight loss drug that really works, it is worth noting that while rimonabant produced weight loss in research subjects that was statistically significant, the magnitude of the actual weight loss was relatively small. This was not a miracle drug; while it modified obesity, it did not take obese people and make them svelte. After years of clinical trials, everyone has apparently concluded that the modest benefit provided by this drug was not worth the risk of side effects.

Here is a case where the FDA should be congratulated for its caution.

Sanofi-Aventis should also be congratulated for its decision to withdraw a drug that, no doubt, cost them hundreds of millions of dollars to develop and test. The company took a very expensive risk in developing rimonabant, and the risk failed. We should all try to keep in mind (as we consider government action to curb the "obscene" profits of drug companies) that profits are realized only after they take risks like this, and that continued progress requires the continued willingness to take such risks and the continued willingness to absorb expensive failures like this one.