US FDA seeks more data on Sanofi-Aventis sleep drug eplivanserin (Ciltyril)

Sanofi-Aventis said that the US FDA has requested additional information regarding benefit-risk regarding the company’s New Drug Application (NDA) for insomnia treatment eplivanserin (Ciltyri).

Sanofi- Aventis’s eplivanserin (Ciltyri) was reviewed by the USFDA as a potential treatment for patients with chronic insomnia characterized by difficulties with sleep maintenance.

Eplivanserin, discovered and developed by Sanofi-Aventis, is a serotonin type 2 A receptor antagonist, and unlike benzodiazepine-receptor agonists (BzRAs), has no affinity for GABA receptors.

Eplivanserin is the furthest along in development of a new nonsedating drug class known as ASTARs, or Antagonists of Serotonin Two A Receptors. Many sleep disorder experts expect the ASTARs to take over a major chunk of the insomnia treatment market now dominated by Zolpidem and other drugs acting on the -[gama]-aminobutyric acid-A receptor.

Sanofi-Aventis studied the insomnia treatment eplivanserin in a clinical development program including nearly 3,000 patients. Sanofi-Aventis said last year that its GEMS Phase III study shows that the 5-HT2A antagonist eplivanserin in development for the treatment of insomnia characterized by sleep maintenance difficulties/nighttime awakenings significantly reduces WASO (Wake time After Sleep Onset) and the number of night-time awakenings reported by the patient at 6 and 12 weeks of treatment, versus placebo.

Sanofi-Aventis study on eplivanserin also showed an improvement of the quality of sleep was also observed in the study. GEMS study results confirmed those of the EPLILONG study (phase III study conducted in similar conditions ), which also showed that eplivanserin significantly reduces WASO and the number of night-time awakenings reported by the patient at 6 and 12 weeks, versus placebo and improves the quality of sleep.

Sanofi study also confirmed eplivanserin’s good tolerance profile versus placebo, with no residual effect on waking and with no rebound phenomenon nor withdrawal symptoms after treatment cessation, as already demonstrated in other studies.

Also, eplivanserin at 5 mg/day resulted in a 64% reduction in the number of nocturnal awakenings, compared with a 36% decrease with placebo. More epli-vanserin-treated patients reported a significant improvement in the refreshing quality of sleep.

The side effect profile of eplivanserin mimicked that of placebo. The exception was dry mouth, which was reported by 1.7% of the placebo group and 5.3% of patients on 5 mg/day of eplivanserin. Sanofi-aventis is currently reviewing the content of the complete response letter, in which the FDA has requested additional information regarding benefit-risk.

Sanofi-Aventis will contact the FDA in the coming days to request a meeting to discuss what steps and data would be needed for approval, the company said in a statement.

The Paris-headquartered Sanofi-Aventis expects that the talks with the FDA go well as it has high hopes for the product. Sanofi has previously said that unlike current hypnotics, eplivanserin is not a sedative and therefore has no after-effects the following morning.

The market for insomnia treatment has been dominated in the past by Sanofi’s own Stilnox/Ambien (zolpidem), which is now available generically and other drugs acting on the gama-aminobutyric acid-A receptor.

Sanofi is currently developing another insomnia treament volinanserin, another 5-HT2A antagonist.

In July, Sanofi-Aventis’ vaccine division, Sanofi Pasteur decided buy Merieux Alliance’s French subsidiary ShanH, which owns 80 percent stake in Shantha Biotechnics for EURO 550 million.

In 2006, Mérieux Alliance had bought 60% stake in Shantha Biotechnics at a valuation of US$175mn. The Britishdrug major GlaxoSmithKline was also in the race to acquire a controlling stake in Shantha Biotechnics. Sanofi’s acquisition of Shantha, which sees sales of around $90 million in the current fiscal year, is expected to be completed by the end of the third quarter.