The US Food and Drug Administration (FDA), has approved the dual antagonist of orexin daridorexant (Quviviq), for the treatment insomnia in adults. The announcement was made by Idorsia the manufacturer of the drug.
The FDA’s decision was result of a phase 3 study of adults with moderate-to severe insomnia. They were randomly assigned to receive 25 or 50 mg of daridorexant, or a placebo. Daridorexant was associated with improvements in the dose of wake-up after sleep as well as total sleep duration and latency to persistent sleep.
Although the overall results are extremely positive however, the improvements in daytime functioning are particularly “exciting,” Thomas Roth, PhD director of the Sleep Disorders and Research Center at Henry Ford Hospital in Detroit, Michigan, told Medscape Medical News.
“That’s sort of a big deal. For me, that’s the biggest deal there is,” said Roth, who was consultant on the design of the phase 3 trial and on the interpretation of the data.
The drug will be offered as 25 mg or 50 mg doses. The FDA suggested that it be declared as a controlled substance. The US Drug Enforcement Administration will schedule daridorexant in May 2022.
Favorable Safety Profile
Insomnia is a very common disorder that is characterized by difficulty getting to sleep or staying asleep, and early morning wake-ups. People who suffer from insomnia frequently report fatigue, irritability, and difficulty with concentration. The condition can also cause serious problems at social and work activities, thus contributing to anxiety or depression.
Like other dual orexin receptor antagonists daridorexant is a competitive antagonist of both orexin receptors in the lateral hypothalamus to block the activity of orexin in a reversible way. This approach decreases the downstream action of the neurotransmitters responsible for promoting wake that are in overactive in patients with insomnia.
The phase 3 trial measured daytime functioning using the Insomnia Daytime Symptoms & Impacts Questionnaire (IDSIQ), a patient-reported outcome instrument. Daridorexant was associated with significant improvements in daytime performance, particularly in sleepiness and mood.
Roth explained that previous trials of dual orexin antagonists did not make use of the IDSIQ to determine their results, therefore it is impossible to compare daridorexant to other drugs in this regard. Researchers also have not conducted head-to-head trials of the drug against other dual orexin receptor antagonists.
Daridorexant has a favorable safety profile. It was not associated with symptoms of withdrawal, insomnia that recurred, or other side effects. The most frequent adverse events were headache and somnolence or fatigue.
“They had no effect on sleep stage distribution [and] they had no significant impact on breathing and sleep in patients who suffer from mild to moderate sleep apnea,” said Roth who presented Phase 3 results at SLEEP 2020.
Roth has been a consultant to Idorsia regarding the design of trials and the interpretation of results.
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