Daridorexant Approved for Adults With Insomnia

The FDA Monday approved a new drug for the treatment of insomnia in adults.

Daridorexant, to be marketed under the name Quviviq, was approved in doses of 25 mg and 50 mg. According to the drugmaker, Idorsia Pharmaceuticals, daridorexant is a dual orexin receptor antagonist, which blocks the binding of the wake-promoting neuropeptides orexins and is believed to turn down overactive wakefulness; other treatments may be sedating, according to the company.

The approval is based on phase 3 trials involving 1854 adults with insomnia at over 160 clinical trial sites in 18 countries.

The clinical trials randomized individuals with insomnia to receive either daridorexant or the placebo once daily, in the evening, for 3 months. Study 1 randomized 930 individuals to daridorexant 50 mg, 25 mg, or placebo; 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, and the 10 mg dose was not approved by the FDA.

The 50 mg dose also demonstrated significant reduction in daytime sleepiness compared with 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 drug also may cause other serious side effects, including sleep paralysis, hallucinations, worsening depression or suicidal thoughts, and “complex sleep behaviors” that are not remembered in the morning, according to the statement from the company.

The FDA recommended that daridorexant be classified as a controlled substance by the Drug Enforcement Administration; it is expected to reach the market in May.