Quviviq improves sleep, daytime functioning in patients with insomnia

Quviviq 25 mg and 50 mg enhanced sleep among patients with insomnia disorder, according to results of two randomized, double-blind, placebo-controlled, phase 3 trials published in The Lancet Neurology.

Quviviq (daridorexant, Idorsia), which recently received FDA approval for treating adults with insomnia, also improved daytime functioning when taken in its 50 mg dose. The treatment exhibited a favorable safety profile.

“The novel dual orexin receptor antagonist, daridorexant, was designed as a medication for insomnia that would have efficacy for sleep onset and sleep maintenance but without any residual effects in the morning that might impair daytime functioning,” Emmanuel Mignot, MD, PhD, the Craig Reynolds Professor of Sleep Medicine at Stanford University and director of the Stanford Center for Narcolepsy, and colleagues wrote. “In phase 2 dose-finding trials, daridorexant improved sleep variables in adults and older adults (aged 65–85 years) with insomnia without causing residual sleepiness the next morning.

“Therefore, we hypothesized that daridorexant might also improve daytime functioning,” they added. “Here, we present the results of two placebo-controlled phase 3 trials (study 1 and study 2), in which we aimed to assess the safety and efficacy of daridorexant in people with insomnia.”

Researchers conducted the multicenter trials at 156 sites in 17 countries among adults with insomnia disorder. Between June 4, 2018, and Feb. 25, 2020, they randomly assigned 930 participants in a 1:1:1 ratio to daridorexant 50 mg, 25 mg or placebo in the first study. Between May 29, 2018, and May 14, 2020, they randomly assigned in a 1:1:1 ratio 924 participants to daridorexant 25 mg, 10 mg or placebo in the second study. In both studies, participants received the intervention every evening for 3 months, with participants, investigators and site personnel masked to treatment allocation. Change from baseline in wake time after sleep onset (WASO) and latency to persistent sleep (LPS), assessed via polysomnography, at months 1 and 3 served as the primary endpoints. Change from baseline in self-reported total sleep time and the sleepiness domain score of the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) at months 1 and 3 served as the secondary endpoints.

In the first study, results showed a significant reduction in WASO and LPS among participants who received daridorexant 50 mg vs. placebo at month 1, as well as among those who received daridorexant 25 mg vs. placebo at months 1 and 3. Those who received daridorexant 50 mg exhibited significant improvement in self-reported total sleep time at months 1 and 3, as well as IDSIQ sleepiness domain scores at months 1 and 3, compared with those who received placebo. Further, those who received daridorexant 25 mg exhibited significant improvement in self-reported total sleep time at months 1 and 3 but not IDSIQ sleepiness domain scores compared with those who received placebo.

In the second study, the daridorexant 25 mg group showed significant reduction in WASO compared with the placebo group at months 1 and 3; however, Mignot and colleagues observed no significant differences in LPS at months 1 or 3. The daridorexant 25 mg group had significantly improved self-reported total sleep time at months 1 and 3 but not IDSIQ sleepiness domain scores compared with the placebo group. Researchers observed no significant differences among participants in the daridorexant 10 mg group for WASO, LPS, self-reported total sleep time or IDSIQ sleepiness domain scores compared with the placebo group.

The treatment groups had comparable overall incidence of adverse events. In all groups, nasopharyngitis and headache represented the most common adverse events. A total of one death occurred in the daridorexant 25 mg group in the first study; however, this was not deemed related to treatment.

“These two studies provide evidence of the efficacy of daridorexant on objective sleep induction and maintenance, on patient-reported sleep quantity and quality, and (at the dose of 50 mg) on daytime functioning — as measured by the IDSIQ sleepiness domain,” Mignot and colleagues wrote. “The highest dose (daridorexant 50 mg) was the most efficacious on night-time and daytime variables, followed by 25 mg, which showed evidence of efficacy only on sleep variables; the 10 mg dose was not efficacious. Daridorexant was well tolerated and safe at all doses.”