The U.S. Food and Drug Administration (FDA) has approved the dual orexin receptor antagonist daridorexant (Quviviq) for the treatment of insomnia in adults, the drug’s manufacturer, Idorsia, announced.
The FDA’s decision was based in part on a Phase 3 study in adults with moderate to severe insomnia who were randomized to receive 25 or 50 mg of daridorexant or a matching placebo. Daridorexant was associated with dose-dependent improvements in wakefulness after sleep onset, total sleep time, and latency to sustained sleep.
While the overall results are very positive, the improvements in daytime function are particularly “exciting,” said Dr. Thomas Roth, director of the Center for Sleep Disorders and Research at Henry Ford Hospital in Detroit, Michigan Medscape Medical News.
“This is a big deal. To me, that’s the greatest thing there is,” said Roth, who served as consultant on the phase 3 study design and data interpretation.
The drug will be available in 25mg and 50mg doses, and the FDA has recommended that it be classified as a controlled substance. Daridorexant is scheduled to be available in May, as planned by the US Drug Enforcement Administration.
Favorable safety profile
Insomnia is a common disorder characterized by difficulty falling asleep or staying asleep and waking up early in the morning. Patients with insomnia often report fatigue, irritability, and difficulty concentrating. The condition can also cause significant problems with work and social activities, contributing to anxiety or depression.
Like other dual orexin receptor antagonists, daridorexant competitively binds to both orexin receptors in the lateral hypothalamus to reversibly block orexin activity. This approach reduces the downstream effects of wakefulness-promoting neurotransmitters, which are overactive in patients with insomnia.
In the phase 3 study, daytime functioning was measured using the new Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), a patient-reported outcome instrument. Daridorexant was associated with significant improvements in daytime functioning, particularly in relation to sleepiness and mood.
Previous studies with other dual orexin receptor antagonists did not use the IDSIQ as a result, so it is not possible to compare daridorexant to these drugs in this regard, Roth noted. The researchers also did not conduct head-to-head studies of the drug with other dual orexin receptor antagonists.
Daridorexant also had a favorable safety profile and was not associated with rebound insomnia or withdrawal symptoms. The most common adverse events were headache and drowsiness or fatigue.
“They had no effect on the distribution of sleep stages [and] they had no significant effects on sleep and breathing in people with mild to moderate sleep apnea,” said Roth, who presented the Phase 3 results at SLEEP 2020.
In addition to advising Idorsia on study design and interpretation of results, Roth has also acted as an advisor to other companies developing sleep aids.
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