Newly published data in Sleep Medicine demonstrates that daridorexant, a dual orexin receptor antagonist (DORA), effectively improves sleep maintenance throughout the entire night while reducing morning sleepiness in patients with chronic insomnia disorder.
The analysis, titled "Effect of daridorexant on nighttime wakefulness and next-morning sleepiness: assessing the transition from night to day in insomnia disorder," provides compelling evidence that daridorexant addresses both nighttime symptoms and daytime impairments associated with insomnia.
Comprehensive Nighttime Efficacy
The Phase 3 data analysis examined 930 patients with insomnia disorder randomized to receive daridorexant 50 mg (n=310), 25 mg (n=310), or placebo (n=310) for three months. Researchers evaluated polysomnography-determined wake after sleep onset (WASO) in each 2-hour quarter of the night during an 8-hour recording period.
At Month 1, both daridorexant 25 mg and 50 mg significantly decreased WASO compared to placebo in the second, third, and fourth quarters of the night. The reductions appeared dose-dependent and increased progressively throughout the night, with the 50 mg dose consistently showing greater effects. Similar results were observed at Month 3.
"Daridorexant works throughout the entire night, especially in the second half of the night when patients need it the most. Remarkably, it achieves this without residual drug effects and even improves morning sleepiness," commented Professor Yves Dauvilliers, MD, PhD, from the University of Montpellier, France, who served as an investigator in the Phase 3 program.
Improved Daytime Functioning
Visual analog scale (VAS) scores for next-morning sleepiness, daytime alertness, and ability to function improved from Day 1 in all treatment groups and continued to improve over time, also showing dose-dependent effects.
Antonio Olivieri, MD, Chief Medical Officer & Head of Global Medical Affairs at Idorsia, attributed these benefits to daridorexant's mechanism of action: "The correlation observed between improvement in morning sleepiness, better daytime alertness, and better ability to function during the day is indicative of the fact that daridorexant is providing restorative sleep and improved days to patients with insomnia disorder."
Dr. Olivieri explained that the dual blockade of orexin receptors, combined with daridorexant's pharmacokinetic/pharmacodynamic profile, results in rapid onset of effect with sufficient duration to cover the night but short enough to avoid negative next-morning residual activity.
Additional Benefits for Patients with Nocturia
A separate crossover trial published in the Journal of Sleep Research further highlighted daridorexant's therapeutic benefits in patients with both chronic insomnia and nocturia (nighttime urination). The study included 60 patients who were randomized to receive either 50 mg daridorexant or placebo for 4 weeks before crossing over to the alternate treatment.
After 4 weeks, daridorexant significantly increased self-reported total sleep time by 56.6 minutes compared to 35.7 minutes with placebo. The medication also reduced the number of nighttime voids, with 53% of daridorexant-treated patients reporting fewer than 2 voids per night after 4 weeks, compared to 32% on placebo.
The timing of the first void was delayed by 31 minutes at week 1 and 23 minutes at week 4 in the daridorexant group compared to placebo, suggesting improved sleep maintenance before the first awakening.
Patient Satisfaction and Daytime Improvements
Patient satisfaction was notably higher with daridorexant, with mean satisfaction scores of 7.0 compared to 5.3 for placebo. At the conclusion of the crossover study, 74% of patients expressed a preference for daridorexant over placebo.
Daridorexant also demonstrated significant improvements in the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) total scores, with greater reductions observed at Week 1 and Week 3 compared to placebo. The mean reduction in IDSIQ score on daridorexant at Week 1 was 16.8, surpassing the clinically meaningful threshold of 17, with maintained improvements at later timepoints.
Safety Profile
Across both studies, daridorexant was generally well-tolerated. In the nocturia crossover trial, no serious adverse events were observed, and no adverse events led to study discontinuation. Relevant treatment-emergent adverse events included somnolence, fatigue, and hangover effect.
About Daridorexant and Insomnia
Daridorexant, marketed as QUVIVIQ by Idorsia, is commercially available in the US, several European countries, Canada, Japan, and Hong Kong. Unlike traditional sleep medications that broadly inhibit brain activity, daridorexant selectively blocks orexin receptors to reduce the overactive wake drive characteristic of insomnia.
Insomnia affects approximately 10% of the global population and is defined as dissatisfaction with sleep combined with significant negative impact on daytime functioning. The condition involves difficulty initiating and/or maintaining sleep on at least three nights per week for at least three months, despite adequate opportunity to sleep.
Research has shown that areas of the brain associated with wakefulness remain more active during sleep in patients with insomnia, highlighting the underlying neurobiological mechanisms that daridorexant targets.
The growing body of evidence supporting daridorexant's efficacy and safety profile suggests it may offer a valuable treatment option for the millions of adults worldwide who struggle with chronic insomnia and its daytime consequences.
