FDA to Review Daridorexant Insomnia Treatment Application

Jean-Paul Clozel, MD

This article was originally published in NeurologyLive.

The US Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) for Idorsia’s daridorexant, an investigational dual orexin receptor antagonist, for the treatment of adult patients with insomnia, according to a recent announcement.

The NDA includes data from a comprehensive clinical and nonclinical developmental program, which demonstrated the efficacy of daridorexant on subjective sleep parameters and an improvement in daytime functioning, while maintaining a favorable safety profile. Idorsia submitted the NDA to the FDA on January 8, 2021 and noted that should they receive approval, daridorexant will launch in the first half of 2022.

"I’m very happy that this first regulatory hurdle is behind us. This was a huge NDA and the team has done an excellent job in preparing the dossier, on which the FDA can judge the properties and merits of daridorexant,” Jean-Paul Clozel, MD, chief executive officer, Idorsia, said in a statement. “We now stand-by to work with the FDA to answer any questions that might arise concerning the effect of daridorexant on sleep, daytime functioning and its safety profile.”

If approved, daridorexant would become the first sleep medication to demonstrate an improvement in sleep and daytime functioning, as measured by the Insomnia Daytime Symptoms and Impacts Questionnaire, while keeping a favorable safety profile in adult and elderly patients.

In April 2020, the company read out data from its first pivotal phase 3 study of daridorexant (NCT03545191), which showed promising results. Doses of both 25-mg and 50-mg daridorexant significantly improved sleep onset and sleep maintenance as measured objectively in a sleep lab by polysomnography. Self-reported data from daily diaries also showed the drug’s significant impact on subjective total sleep time, as well.

The double-blind, randomized, placebo-controlled, parallel-group, phase 3 study included 930 adult and elderly patients with insomnia and evaluated treatment with daridorexant over a 3-month period. In addition to improvements in sleep onset and sleep maintenance, treatment with 25-mg and 50-mg daridorexant also significantly improved total sleep time subjectivity (sTST) compared with placebo.

All 3 of these improvements were seen at both the 1- and 3-month timepoints. That study was part of a larger phase 3 registration program that included another phase 3 study and extension study. In July 2020, the safety and efficacy of daridorexant was confirmed in the publication of a second pivotal phase 3 study.

The latest data demonstrated a statistically significant improvement in sleep maintenance and subjective total sleep time at months 1 and 3 for patients, nearly 40% of whom were 65 or older, who received the 25-mg dose. Additionally, the therapy also demonstrated positive effects on daytime functioning, which were observed in the first phase 3 study as well.

The safety of the drug was consistent across both studies, with treatment-emergent adverse events (TEAEs) reported in 38.2% and 39.3% of patients treated with 10 mg or 25 mg daridorexant compared with 32.7% in the placebo group. The most common TEAEs observed were nasopharyngitis, headache, somnolence, and fatigue. Notably, no cataplexy-like events or next-morning residual effects were reported, and no suicide or self-injurious behavior was observed.