Merck & Co has suffered a major setback on the clinical front with the news that the firm has halted development of its investigational obesity drug taranabant.

The New Jersey-based drugmaker has pulled the plug on taranabant, which blocks cannabinoid type 1 receptors in the brain, after Phase III data showed that both “efficacy and adverse events were dose-related, with greater efficacy and more adverse events in the higher doses”. John Amatruda, research head for diabetes and obesity, said that “after careful consideration, we determined that the overall profile of taranabant does not support further development for obesity”.

The side effects caused by the drug relate to psychiatric problems such as depression, anxiety and irritability, while patients also reported statistically significant weight loss, compared with those on placebo. Phase II data published earlier this year also demonstrated that patients taking the higher dosages of taranabant suffered more from side effects such as nausea and vomiting.

That Merck has decided not to continue with taranabant comes as no great surprise, given the experience of Sanofi-Aventis’ Acomplia (rimonabant), which also blocks cannabinoid receptors in the brain, the same receptors that cause people to get the ‘munchies’ when smoking marijuana. Though approved in Europe and in some other markets, Zimulti (as Acomplia would be known in the USA) was rejected unanimously in June 2007 by a Food and Drug Administration advisory panel which said that its benefits do not outweigh the risk of psychiatric adverse effects, including suicide and seizures.

The termination of taranabant would appear to spell the end for CB-1 receptor antagonists as potential treatments for obesity. Pfizer is still conducting Phase III trials on CP-945598 (otenabant), but seeing as the firm said earlier this week that it is getting out of early-stage research in obesity, among a number of other therapeutic areas, hopes are not overly high for the future of the compound.