Newly Approved Daridorexant Demonstrates Safety, Continued Efficacy at 1-Year

At months 6, 9, and 12 of treatment with daridorexant—which was recently FDA-approved for insomnia—patients improved on several sleep measures, including subjective total sleep time and daytime functioning.

After receiving FDA approval for the treatment of insomnia in adults in January, new data suggest that patients treated with Idorsia’s daridorexant (Quviviq), continued to show improvements of night-time and daytime symptoms after 1 year of treatment, with no evidence of tolerance or dependency.1

The findings, presented at the World Sleep Congress, March 11-16, in Rome, Italy, are from an extension study (NCT03679884) of 2 pivotal phase 3 studies (NCT03545191; NCT03575104) that helped lend to the therapeutic’s approval. In the extension, 804 adults (18-64 years) and elderly (≥65 years) patients with insomnia who completed the 12-week double-blind treatment and 7-day placebo run-out were included in the analysis.

Led by Dieter Kunz, MD, head of the Department of Sleep Medicine, St. Hedwig Hospital, the extension period was 40 weeks, followed by a 7-day placebo run-out. Patients originally randomized to daridorexant (10 mg: n = 142; 25 mg: n = 270; 50 mg: n = 137) stayed on their respective treatments, while those randomized to placebo were re-randomized to daridorexant 25 mg (n = 127) or placebo (n = 128).

Daridorexant, a dual orexin receptor antagonist, resulted in a similar incidence of treatment-emergent adverse events (TEAEs) across groups (35-40%), most of which were mild or moderate in severity, with no dose-dependent pattern observed as well. Nasopharyngitis was the most common TEAE reported in daridorexant-treated patients. This patient group also showed a low incidence of serious TEAEs (<5.5%).

Improvements on subjective total sleep time (sTST) and daytime functioning, assessed using Insomnia Daytimes Symptoms and Impacts Questionnaire (IDSIQ), were observed at 3 months and sustained until the 12-month time point. The most pronounced improvements were observed in the 50-mg group, represented by mean increases of 67.7 (SD, 68.65), 68.9 (SD, 65.89), and 75.6 (SD, 69.90) minutes in sTST from baseline to months 6, 9, and 12, respectively. For the 25 mg group, these patients saw mean improvements of 58.06 (SD, 58.61), 65.1 (SD, 58.75), and 66 (61.09) minutes, at the 6-, 9-, and 12-month periods, respectively, compared with improvements of 50.3 (SD, 65.73), 59.0 (SD, 62.62), and 62.6 (SD. 72.42) minutes in the placebo group.

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For ISDIQ total score, mean reductions from baseline at months 6, 9, and 12, were –25.6 (SD, 25.79), –24.9 (SD, 25.35), and –27.3 (SD, 25.48), respectively, for daridorexant 50 mg, –20.3 (SD, 22.55), –22.2 (SD, 23.28), and –22.8 (SD, 26.50) for 25-mg group and –14.7 (SD, 21.72), –16.8 (SD, 20.82), and –19.1 (SD, 24.15) for placebo. Patients across the treatment groups demonstrated similar improvements in IDSIQ sleepiness, alert/cognition, and mood domain scores.

There were 2 deaths recorded in the extension, both cardiovascular-related and not deemed related to treatment. Investigators also recorded AEs of special interest (AESIs), which included symptoms related to excessive daytime sleepiness or complex sleep behaviors, suicidal ideation/self-injury. There were 2 nonserious AESIs of somnolence (25 mg) and abnormal dreams (50 mg) were reported with daridorexant and 1 serious AESI of suicidal ideation with placebo.

Fifteen patients on daridorexant reported accidental overdose, all incidences of which were asymptomatic. Somnolence was reported in 7 patients receiving daridorexant, all of which were nonserious. Kunz et al did not find any evidence of withdrawal-related symptoms or rebound after treatment discontinuation.

After receiving approval from the FDA, Idorsia noted that it expects the drug to be available in May 2022. The basis for the decision came from a robust clinical program that included 1854 adults across 160 clinical trial sites. In those studies, treatment with 25-mg and 50-mg daridorexant resulted in greater improved outcomes of sleep onset and sleep maintenance relative to placebo.2

Daridorexant, designed to block the wake-promoting neuropeptides orexins, also showed statistically significant improvements in sleep and daytime functioning, as measured by the Insomnia Daytime Symptoms and Impacts Questionnaire, while keeping a favorable and safe profile.

Following daridorexant’s FDA approval, NeurologyLive® hosted a special podcast episode featuring Thomas Roth, PhD, director, Sleep Disorders and Research Center, Henry Ford Hospital; professor of psychiatry, Wayne State University School of Medicine; and clinical professor of psychiatry, University of Michigan College of Medicine. Listen in below as Roth, who was an investigator in the clinical development studies of the newly approved Idorsia therapy, offered insight into the known efficacy and safety profiles, as well as some context to its potential impact on the therapeutic landscape of insomnia.

1. Kunz D, Benes H, Garcia-Borreguero D, et al. Long-term safety and efficacy of daridorexant in patients with insomnia disorder. Presented at SLEEP 2022; March 11-16. Abstract 2145
2. Idorsia receives US FDA approval of Quiviviq (daridorexant) 25 and 50 mg for the treatment of adults with insomnia. News release. Idorsia. January 10, 2022. Accessed March 11, 2022.