Daridorexant Effective for Insomnia in Phase 3 Trial

Jean-Paul Clozel, MD

Top-line results from a study of daridorexant in adults with insomnia demonstrate the agent’s efficacy on objective and subjective sleep parameters, as well as daytime performance with no residual effect in the morning and no evidence of rebound or withdrawal symptoms upon treatment discontinuation, according to Idorsia, the developer of the dual orexin receptor antagonist.

Doses of both 25 mg and 50 mg daridorexant significantly improved sleep onset and sleep maintenance as measured objectively in a sleep lab by polysomnography. Self-reported data from daily diaries showed the drug’s significant impact on subjective total sleep time, as well.

“While we designed daridorexant to have the optimal profile for a sleep medicine, I am none-the-less stunned by the results,” Jean-Paul Clozel, MD, chief executive officer, Idorsia, said in a statement. “Once approved, by providing daridorexant to the millions of patients with insomnia, Idorsia will have a major impact on this medical, social, and economic problem. With these results Idorsia is entering into a new era; less than 3 years since its creation, Idorsia is taking a huge step forward in delivering on the vision to become a fully-fledged biopharmaceutical company.”

The double-blind, randomized, placebo-controlled, parallel-group, phase 3 polysomnography study assessed the efficacy and safety of daridorexant on objective and subjective sleep and daytime performance parameters in 930 adult and elderly patients with insomnia over a 3-month period.

The study is part of a phase 3 registration program that includes another phase 3 study and extension study. The additional phase 3 study is ongoing and will assess treatment with 10 mg and 25 mg doses over 3 months and is expected to readout results in the third quarter of 2020. The 40-week extension study is expected to enroll around 1800 patients and will measure the effect of all 3 doses while generating long-term data for the treatment of insomnia.

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In addition to the previously stated improvements in sleep onset and sleep maintenance, treatment with 25 mg and 50 mg daridorexant significantly improved total sleep time subjectivity (sTST) compared with placebo. All 3 of these measures showed significant improvement at both the 1- and 3-month timepoints. Investigators measured the impact on patients’ daytime performance using the sleepiness domain score from the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ).

At both month 1 and month 3, daytime performance results, as measured by patients feeling less physically and mentally tired, were significant in the 50 mg group and showed a numerical trend in the 25 mg group.

The occurrence of treatment-emergent adverse events (TEAE) were similar in each dose group, with 37.7% of patients treated with either 25 or 50 mg daridorexant experiencing TEAEs compared with 34.0% of those who received placebo. Nasopharyngitis and headache had a 3% incidence, the highest of any TEAE.

The number of adverse events (AEs) was similar in both dose groups, but the number of serious AEs was greater in placebo than either of the 2 daridorexant dose groups (25 mg: n = 2; 50 mg: n = 3; placebo: n = 7).

Upon discontinuation, there was no rebound insomnia or withdrawal symptoms. Researchers noted no suicide, suicidal ideation, or self-injury were reported, as well.

“The results from this pivotal study are truly remarkable for the consistency of the benefit in sleep measures,” Guy Braunstein, MD, head of Global Clinical Development, Idorsia, said in a statement. “Moreover, this is the first study to demonstrate an insomnia product can improve how the patient feels during the day. If you ask anybody who suffers from insomnia that is what they want—to sleep longer and feel better during day. Daridorexant is addressing real patient problems.”

REFERENCE

Idorsia announces positive results in the first phase 3 study of daridorexant with improved sleep and daytime performance of patients with insomnia [news release]. Allschwil, Switzerland: Idorsia; Published April 20, 2020. Accessed April 21, 2020. globenewswire.com/Resource/Download/5e621287-915d-4574-95a3-74b93b647170.