Novartis and Servier are developing
agomelatine for the treatment of depression.
Agomelatine is a specific
melatonin (MT1 and
MT2) receptor agonist that also has antagonistic activities at serotonin-(2C) (5-HT(2C)) receptors. Novartis believes
agomelatine is comparable to current standard
therapies for depression with improved tolerability, including a low propensity to cause sexual dysfunction and
weight gain. Clinical development is being conducted in the US for the treatment of depression; approval for this indication was declined in the EU, apparently due to insufficient data. Servier has also conducted a trial of the agent in patients with generalized
anxiety disorder in France, South Africa and Finland, and a phase II trial in
sleep disorders in France. In March 2006, Servier and Novartis signed a licensing agreement for
agomelatine. Novartis obtained the exclusive rights for the development and marketing of
agomelatine in the US and several other countries. Servier retained the rights to the product in the rest of the world. The clinical development plan for
agomelatine includes phase III trials being conducted under the
parAGOn clinical trial programme. One US-based trial that began in March 2007 (NCT00463242) is recruiting 490 patients with depression who will receive placebo or
agomelatine 25 or 50 mg for 8 weeks and will then receive open-label
agomelatine for 52 weeks. Novartis is also conducting an 8-week phase III trial (NCT00411099) comparing the safety and efficacy of
agomelatine 25 and 50 mg in patients with
major depressive disorder. A follow-up, 52-week open-label extension study (CAGO178A2301E) will also be conducted. Another phase III study underway is NCT00411242, which has the same design and is also followed by a 52-week open-label extension study (CAGO178A2302E). These studies are all expected to be completed by January 2009. In July 2006, the Committee for Medicinal Products for Human Use recommended the refusal of marketing authorisation for
agomelatine for the treatment of depression. Servier had applied for a re-examination of the finding but withdrew the request in November 2006. Servier's MAA was not supported due to insufficient data and no recent development has been reported in this indication in the EU.
Agomelatine prevented relapse in patients with depression compared with placebo and was well tolerated in an international phase III trial.