Daridorexant Provides Relief for Insomnia in Women During Menopausal Transition

A subgroup analysis from a large-scale, phase 3 study (NCT03545191) revealed that daridorexant (Quivivq; Idorsia) at 50 mg doses may provide benefits in sleep onset, sleep maintenance, and daytime functioning in women with insomnia disorder in menopausal transition age.^1,2

Presented at the World Sleep Congress, held September 5-10 in Singapore, the findings represent the first evaluation of daridorexant in women with insomnia disorder during the menopausal transition age. Approved in 2022, daridorexant is among the dual orexin receptor antagonist (DORA) class, working by blocking the binding of orexin-A and orexin-B neuropeptides to their receptors.

The post-hoc analysis included women aged 47-55 years with insomnia from a larger phase 3 trial who received either daridorexant 50 mg (n = 35), 25 mg (n = 43), or placebo (n = 39). At months (M) 1 and 3, both daridorexant doses showed improved wake after sleep onset (WASO), with the most pronounced effects observed in the higher dose group (50 mg: M1: least square mean [LSM] change, –42.4 min [95% CI, –52.5 to –32.3]); M3: –42.9 min [95% CI, 53.5 to –32.3]); placebo: M1: –12.7 min [95% CI, –22.4 to –3.0]; M3: –29.1 min [95% CI, –40.0 to –18.3]).

Continued data from the analysis showed improvements in latency to persistent sleep (LPS) and self-reported total sleep time (sTST) that were numerically greater at M3 with daridorexant 50 mg vs placebo and 25 mg. At that time point, those in the higher dose group had LSM changes of –34.2 and 75.3 in LPS and sTST, respectively, compared with changes of –23.3 and 53.5 for placebo.

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Led by Zoe Schaedel, MRCGP, DRCOG, a menopause specialist at KIMS Hospital, the study also revealed showed differences in Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), an outcome of insomnia-related daytime impairment. While the daridorexant 25 mg group had little effect vs placebo, those in the higher dose group showed improvements in IDSIQ at M1 (LSM, –14.7; 95% CI, –20.4 to –8.9) and M3 (LSM, –21.9; 95% CI, –29.3 to –14.5).

In terms of safety, treatment-emergent adverse events (TEAEs) occurred in 46% of those in the daridorext high-dose group, 35% of those on 25 mg, and 38% of those on placebo. In total, 2 serious AEs and 2 TEAEs leading to treatment discontinuation were reported, all within the placebo group. Nasopharyngitis, which occurred in 4 patients in the 50 mg group (11%), 2 (5%) in the 25 mg group, and 5 (13%) in the placebo group, was the most common TEAE. Other TEAEs included headache, gastroenteritis, back pain, influenza, and somnolence, although all infrequent in both groups.

Visual Analogue Scale (VAS), a key safety end point assessing morning sleepiness, was also improved in both daridorexant dosed groups as well as placebo from baseline to M1 and M3. Within the active groups, investigators reported 3-month mean changes of 14.1 (SD, 18.5) for the 50 mg group, 14.8 (SD, 19.3) for the 25 mg group, and 15.7 (SD, 20.6) for the placebo groups, over that time. For context, higher VAS scores indicated less morning sleepiness.

REFERENCES
1. Idorsia shares new analyses of daridorexant for patients with insomnia at World Sleep 2025. News release. Idorsia. September 10, 2025. Accessed September 15, 2025. https://www.globenewswire.com/news-release/2025/09/10/3148005/0/en/Idorsia-shares-new-analyses-of-daridorexant-for-patients-with-insomnia-at-World-Sleep-2025.html
2. Schaedel Z, Bakker T, Bassetti C, et al. Efficacy and safety of daridorexant in women with insomnia disorder during menopausal transition: a subgroup analysis. Presented at: World Sleep Congress; September 5-10; Singapore.