FDA Approves Daridorexant for Treatment of Insomnia

The FDA has approved daridorexant (Quviviq, Idorsia Pharmaceuticals) for the treatment of individuals with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.

The FDA approval of daridorexant at 25 mg and 50 mg doses is based on an extensive clinical program that included 1854 individuals with insomnia at more than 160 clinical trial sites across 18 countries.

“As noted in the definition of insomnia, the disorder is not only a problem of the night but affects a patient’s ability to function during the day. Although the personal and societal burden of insomnia is well established, elevating the impact insomnia has on both the night and day remains critical in addressing patients’ needs,” said Thomas Roth, PhD, director of the Sleep Disorder and Research Center at Henry Ford Hospital, in a press release.

Daridorexant is a dual orexin receptor antagonist that blocks the binding of neuropeptides orexins, which is connected to sleep/wake regulation. The drug is thought to turn down overactive wakefulness, as opposed to sedating the brain, according to Idorsia Pharmaceuticals.

During the phase 3 clinical program, daridorexant demonstrated significant improvement on the objective measures of sleep onset and sleep maintenance, as well as individual reported total sleep time versus the placebo, according to Idorsia Pharmaceuticals.

The 50 mg dose of daridorexant, which was evaluated in 1 of the 2 studies, demonstrated a significant reduction in patient-reported daytime sleepiness, using a valid instrument, and is consistent with the United States prescribing information.

“Daridorexant properties include a potent inhibition of both orexin receptors, a rapid absorption for sleep onset, and a pharmacokinetic profile such that around 80% of daridorexant has been eliminated after a night of sleep to help minimize residual effects,” said Martine Clozel, MD, chief scientific officer of Idorsia, in the release.

The clinical trials randomized individuals with insomnia to receive either daridorexant or the placebo once daily, in the evening, for 3 months. One study randomized 930 individuals to daridorexant 50 mg, 25 mg, or placebo, whereas study 2 randomized 924 individuals to daridorexant 25 mg, 10 mg, or placebo.

At the end of the 3-month treatment period, both studies included a 7-day placebo run-out period, after which individuals could enter a 9-month, double-blind, placebo-controlled extension study. Approximately 600 individuals received at least 6 months of cumulative treatment, including 373 who were treated for at least 12 months.

The primary efficacy endpoints for both studies were the change from baseline to month 1 and month 3 in Latency to Persistent Sleep—a measure of sleep induction—and Wake After Sleep Onset (WASO)—a measure of sleep maintenance—measured objectively by polysomnography in a sleep laboratory.

The secondary endpoints included in the statistical testing hierarchy with type I error control were patient-reported Total Sleep Time (sTST), evaluated every morning at home using a validated sleep diary questionnaire.

In study 1, doses of 25 mg and 50 mg showed a statistically significant improvement in all 3 measurements against the placebo, at both months 1 and 3. In study 2, the 25 mg dose showed statistically significant improvement on WASO and sTST at months 1 and 3 when compared to the placebo. The 10 mg dose did not show significant improvement on the 3 measurements.

The 50 mg dose also demonstrated significant reduction in daytime sleepiness compared to the placebo, as measured by the sleepiness domain score from the Insomnia Daytime Symptoms and Impacts Questionnaire at months 1 and 3. Results on this endpoint for the 25 mg dose did not reach statistical significance in either study at both timepoints.

The most common adverse events were headache and somnolence or fatigue.

The 10 mg dose is not an approved dose by the FDA.

The FDA recommended that daridorexant be classified as a controlled substance and the drug is anticipated to be available in May 2022, following scheduling by the US Drug Enforcement Administration.

Reference

Idorsia receives US FDA approval of Quviviq (daridorexant) 25 and 50 mg for the treatment of adults with insomnia. Idorsia. News release. January 10, 2022. Accessed January 10, 2022. https://www.idorsia.us/documents/us/media-releases/2201_us-fda-approval-quviviq-announcement.pdf