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FDA approves Quviviq (daridorexant, Idorsia) for treating patients with insomnia. Phase 3 clinical trials published in in The Lancet Neurology aimed to demonstrate the use of 25 mg and 50 mg of Quviviq in adults with insomnia. Clinical findings show that when the drug is taken at a dose of 50 mg, it improves daytime functions in addition to insomnia treatment. The treatment is safe and effective.
Mechanism of action
Daridorexant is a dual orexin receptor antagonist, that was specifically created for the treatment of insomnia. According to Emmanuel Mignot, professor at Stanford University, this drug has the potential to enhance sleep onset efficacy and sleep maintenance, without disrupting the daytime functions. Thus, quviviq does not cause any residual effects in the morning.
Results of phase 2 trials demonstrated that the drug has a beneficial outcome in older individuals (65-85 years) and adults. Improvement in sleep variables without presence of residual tiredness and sleepiness in the morning. Similarly, it was hypothesized that daridorexant may enhance daytime functioning.
Clinical trials
Two phase 3 clinical trials were conducted to investigate the efficacy and safety of daridorexant in patients with insomnia.
The study was conducted in 17 countries at 156 sites including patients with insomnia disorder.
- First study: Study performed between 2018-2020. It included 930 participants, distributed in three groups of 50mg, 25mg, and placebo (1:1:1 ratio).
- Second study: Study performed between 2018-2020. It included 924 participants, distributed in three groups of 25mg, 10mg, and placebo (1:1:1 ratio).
Outcome assessment
Both the studies evaluated the changes in wake time after onset of sleep (WASO) and latency to persistent sleep (LPS). The response was assessed through polysomnography, at 1 and 3 months as the primary outcome measure. The secondary outcome measure was changes in self-reported total sleep time and sleep related score of the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ).
The results demonstrated:
- Significant changes in LPS and WASO in participants who received 50mg compared to the placebo group at 1 month.
- Significant changes in LPS and WASO in participants who received 25mg compared to the placebo group at 1 and 3 months.
- Improvement in self-reported total sleep time in participants who received 50 mg compared to the placebo group at 1 and 3 months
- Changes in sleep score of IDSIQ domain in participants who received 50 mg compared to the placebo group at 1 and 3 months
- Participants who received 25mg of daridorexant demonstrated improvement in self-assessed total sleep time at 1, and 3 months. However, no statistically significant change in IDSIQ sleepiness domain scores was observed.
Adverse events
The treatment groups had some adverse events. The most common side-effects were headache and nasopharyngitis. In 25mg daridorexant group, death of a patient occurred, although this was not directly associated with the treatment.
Clinical efficacy
The studies demonstrated significant improvements in sleep induction and maintenance.
Improvement in sleep quality and quantity as well as daytime functioning as expressed by the IDSIQ sleepiness domain.
A dose of 50mg proved clinically more efficacious in improving nigh-time and daytime variables compared to the 25mg dose.
Daridorexant was well-tolerated and had a safe profile at all dosages.
