Daridorexant Receives Approval for Insomnia Treatment

On January 7, 2022, the FDA approved daridorexant (Quviviq) for the treatment of adults with insomnia.¹ The approval was based on findings from a phase 3 clinical trial program in which the drug successfully demonstrated significant improvement in sleep onset, sleep maintenance, and patient- reported total sleep time.²

Efficacy

Two multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 trials (study 1, NCT03545191; study 2, NCT03575104) evaluated efficacy. Investigators randomly assigned 1854 patients to receive daridorexant or placebo once in the evening for 3 months. Study 1 included 930 participants who received daridorexant 50 mg, 25 mg, or placebo (n = 310 for all). Study 2 participants received daridorexant 25 mg, 10 mg, or placebo (n = 309, 307, and 308, respectively).

The primary efficacy end point was change from baseline in latency to persistent sleep (LPS)

and wake after sleep onset (WASO), measured by polysomnography at months 1 and 3. Secondary end points included patient-reported subjective total sleep time (sTST), recorded using a validated sleep diary questionnaire.

At months 1 and 3, study 1 participants who received 25 mg or 50 mg demonstrated statistically significant improvements in LPS, WASO, and sTST; study 2 results showed that 25 mg led to a statistically significant improvement vs placebo in WASO and sTST. No statistically significant improvement was noted in the 10 mg group.

Safety

The safety profile of daridorexant was established through 3 placebo-controlled studies: study 1, study 2, and a phase 3, 9-month extension study of eligible patients from the first 2 studies (NCT03679884). In the extension study, 804 participants were randomly assigned to receive daridorexant 50 mg, 25 mg, or 10 mg; placebo; or daridorexant 25 mg/ex-placebo.

The most common adverse events in the 25-mg, 50-mg, and placebo groups, respectively, were headache (6%, 7%, 5%), somnolence/fatigue (6%, 5%, 4%), dizziness (2%, 3%, 2%), and nausea (0%, 3%, 2%). Rare occurrences of sleep paralysis were reported in the 25-mg and 50-mg groups, and hypnagogic/hypnopompic hallucinations were reported in the 25-mg group.

A randomized, double-blind, placebo- and active-controlled 4-way crossover study assessed the next-day effects of the medication on driving after doses of 50 mg and 100 mg. The difference in performance after the first dose, measured by change in standard deviation of lateral position, was significant compared with placebo for both dose groups. However, the mean effect after 4 days of treatment was not significant. Patients should be cautioned about next-day driving impairment when initiating treatment.

The use of daridorexant is contraindicated in patients with severe hepatic impairment; a maximum daily dose of 25 mg is recommended in those with moderate impairment. Concomitant use with strong CYP3A4 inhibitors should be avoided. Concomitant use with moderate inhibitors of CYP3A4 may be considered, but the maximum daily dose should not exceed 25 mg.

Daridorexant is a schedule IV medication with potential for abuse due to its central nervous system depressant effects.

Drug Administration

Daridorexant is for the treatment of adult patients with insomnia and is supplied as an arc triangle–shaped, film-coated oral tablet. The recommended dosage range is 25 mg to 50 mg taken by mouth, no more than once per night within 30 minutes of going to bed. There should be at least 7 hours remaining prior to planned awakening. Time to sleep onset may be delayed if daridorexant is taken with or soon after a meal.

References

1. QUVIVIQ [package insert]. Radnor, PA. Idorsia Pharmaceuticals US Inc. January 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214985s000lbl.pdf

2. Idorsia receives US FDA approval of QUVIVIQ (daridorexant) 25 and 50 mg for the treatment of adults with insomnia. News release. Idorsia. January 10, 2022. Accessed May 11, 2022. https://www.idorsia.com/media/news-details?newsId=2665386