Dawn has broken for obesity treatment with cannabinoid receptor (CB1) antagonists

Barcelona, Spain | Feb 23, 2006 | The Business Intelligence firm La Merie S.L. reported today that the proven clinical efficacy of the CB1 receptor antagonist rimonabant in obesity has greatly stimulated the discovery of novel CB1 antagonists. Sanofi-Aventis’ first-in-class once-daily oral drug now received an approvable letter from the FDA for weight management. Sanofi-Aventis leads the field with two further CB1 antagonists and is exploring their use in patients with cognitive defects. Three other companies have clinical stage projects, three companies are close to initiating phase I studies and more than six companies are active in discovery of CB1 antagonists. These results and more were found in a search conducted by La Merie Business Intelligence published in the February 20 issue of R&D Pipeline News, edited by La Merie. The competitor analysis of CB1 antagonists can be acquired at www.pipelinereview.com, La Merie’s News Center and Online Store.

Rimonabant has been studied in more than 6,000 patients. Results of the RIO-LIPIDS study showed that a one-year treatment of overweigth and obese patients with abnormal lipid levels with once daily rimonabant significantly reduced body weigth by an average of 6.9 kg in comparison to a loss of 1.5 kg in the placebo group. Rimonabant also decreased waist circumference by 7.1 cm versus 2.4 cm in the placebo group. More importantly, it improved a range of cardiometabolic risk factors that may contribute to type 2 diabetes and heart disease. Results of a two-year treatment with rimonabant in the RIO-North America study evidenced sustained effects on waist circumference, body weight and cardiometabolic risk factors. Mechanism-based adverse effects associated with CB1 receptor antagonists have not been reported.

The mechanism of action of CB1 antagonists still is not yet fully understood. Data indicate a loss of appetite as well as an increase in metabolic rate and a loss of fat mass. In addition, it has been shown that cannabinoid antagonists can prevent drug reinstatement with cocaine, alcohol and nicotine. Sanofi-Aventis had studied rimonabant as an aid to smoking cessation and submitted an NDA based on studies for up to one year in over 6,500 smokers. However, the FDA issued a non-approvable letter for this indication.


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