US FDA delays Sanofi-Aventis's sleeping pill with complete response letter

The US FDA has issued Sanofi-Aventis a complete response letter for its chronic insomnia drug Ciltyri (eplivanserin), requesting further information on the drug's benefit-risk profile.

The company is currently reviewing the complete response letter, and will meet with the agency over the next few days to discuss what steps are needed for approval.

The 5HT2A receptor antagonist has been viewed by some as Sanofi-Aventis's key to maintaining a share of the sleep market. The company once held around 67% of the sleep market and its Ambien (zolpidem tartrate) was once a multi-billion dollar blockbuster drug, although it still had sales of €447 million in the first half of this year despite having lost patent protection. A company spokesman would not comment on the anticipated sales of the new drug, if approved.

Sanofi-Aventis had also been testing volinanserin, another 5HT2A receptor antagonist, for insomnia in a Phase III trial, but development of this drug was discontinued earlier this year, leaving Ciltyri as the only sleep drug in the company's clinical pipeline.

Ciltyri has been tested in over 3,000 insomnia patients in Phase III trials. These trials, said the company, showed that the drug was generally well tolerated versus placebo, with no residual effect on waking or withdrawal symptoms after treatment cessation.

In GEMS, a recently completed Phase III trial, the most frequently reported adverse events were dizziness, upper respiratory tract infection, dry mouth, anxiety, depression, gastroenteritis, diverticulitis, urinary tract infection, pharyngolaryngeal pain and vertigo. No rebound insomnia or meaningful withdrawal symptoms were observed during the two-week run-out period.

Ciltyri is the leading 5HT2A receptor antagonist drug candidate for the treatment of insomnia. It was previously in development for depression, schizophrenia, anxiety and fibromyalgia, but none of these programmes proceeded beyond Phase II trials.

Lilly's LY-2624803, Intra-Cellular Therapy's ITI-722 and Acadia's pimavanserin tartrate have the same mechanism of action and have reached Phase II development for the same indication.

Other compounds that act as 5HT2A receptor antagonists have been launched for various neurological indications including schizophrenia, psychosis and depression.