Updated March 26, 2015.

By DrRich

February 18, 2006

Updated February 21, 2006

A few days after the latest clinical results with rimonabant were published in the Feb. 15 issue of the Journal of the American Medical Association, the Food and Drug Administration declined to approve this widely anticipated new drug, according to the February 18 issue of the Wall Street Journal. Rimonabant (Sanofi-Aventis) has been causing excitement among physicians and patients alike during the past several years.

Over that time, randomized clinical trials have shown that the drug can help with both sustainable weight loss and with smoking cessation.

According to company spokesmen, the FDA last week issued an "approvable" lettter for the weight loss indication, but a "non-approvable" letter for smoking cessation. The "approvable" letter for weight loss apparently is not a blanket approval, but places undisclosed requirements on Sanofi-Aventis before the drug can be marketed. It is not immediately clear when the company will be able to meet these undisclosed requirements for the weight loss indication, or whether it will continue pursuing the smoking cessation indication, now that this claim has been rejected.

Early trials with rimonabant were very promising, and while many have cautioned that it's way too early to get very excited about this drug, such cautions have been largely ignored. People have been chomping at the bit to get at rimonabant.

Rimonabant is the first of a class of drugs, called CB1 blockers, that act on the endocannabinoid system (the EC system), a natural system that modulates the body's energy balance and nicotine dependence.

An over-stimulated EC system is thought to play a role both in obesity and in tobacco dependence, and CB1 blockers are supposed to reduce this overstimulation.

The latest published clinical trial with rimonabant, the RIO-North America study, showed that in 3040 patients treated for two years, 20 mg of rimonabant produced a significant reduction in weight, waist circumference, triglycerides, and in the percentage of patients with metabolic syndrome, as well as a significant increase in HDL levels, compared to placebo. Disturbingly, however, 50% of patients in both the rimonabant and placebo groups (and patients did not know which group they were in) dropped out before the study was finished. Furthermore, to maintain the favorable results, chronic therapy with rimonabant - which will be a very expensive drug - appears necessary. In addition, while the weight loss and reduction in waist circumference were statistically significant as compared to placebo, they were not of impressive magnitude. The average weight loss over 2 years was about 15 pounds, and the average reduction in waist size was 2 - 4 inches. And finally, about 6% of patients on rimonabant reported anxiety, and 5% reported feeling depressed.

DrRich comments:

Here's what we can say about rimonabant: 1) It is effective in producing sustained weight loss. 2) The weight loss it produces is not of sufficient magnitude as to change a person's life; it is a modest weight loss. 3) Everybody and his mother will be clamoring for this drug once it is approved. 4) It will be very expensive. (It has taken Sanofi hundreds of millions of dollars to get the drug to this stage, including paying tens of millions for various randomized clinical trials. They have a limited number of years to get their money back and make a profit before the patent runs out. I don't care if it costs a penny a pill to manufacture. This drug will have to be very expensive, or no drug company would ever take such a financial risk again.) 5) Despite the fact that thousands of patients have been enrolled and followed in clinical trials with rimonabant, we have no real idea as to what side effects might show up when hundreds of thousands or millions of patients (i.e. all the patients clamoring for this drug) begin taking it.

I suspect that, regarding the use of rimonabant for weight loss, the FDA is just being cautious, and that the requirements they have placed on Sanofi-Aventis will be related to trying to figure a way they can legally manage the onslaught of demand, and accurately tabulate the drug's ultimate risk/benefit ratio, once the drug is approved for weight loss. I have no idea why the smoking cessation claim was blocked entirely, as the company has not chosen to reveal the content of the "non-approvable" letter for this indication.