Idorsia announced positive top-line results of the second pivotal Phase 3 study investigating 10 and 25 mg doses of its dual orexin receptor antagonist, daridorexant, in 924 adult and elderly patients (39.3% ≥ 65 years) with insomnia.
The study confirms the findings of the first pivotal study, demonstrating efficacy of treatment with daridorexant on objective and subjective sleep parameters and showed positive effects on daytime functioning, with patients reporting no morning sleepiness and no evidence of rebound or withdrawal symptoms upon treatment discontinuation.
On April 20, 2020, the company reported (media release) the results of the first pivotal study with daridorexant where both 25 and 50 mg daridorexant significantly improved both sleep onset and sleep maintenance. Daridorexant 50 mg also significantly improved daytime functioning. All results were sustained over the 3 months of the trial.
In the second study, daridorexant 25 mg significantly improved sleep maintenance as measured objectively in a sleep lab by polysomnography. Daridorexant 25 mg also significantly improved subjective total sleep time as measured daily with a patient diary at home. The results were statistically significant at month 1 and at month 3 for these sleep measures, showing sustained benefit.
Furthermore, the effect of daridorexant 25mg on sleep onset and daytime functioning were numerically consistent with the effects seen in the first study. However, due to the control of the Type 1 error rate for 16 comparisons, these endpoints – despite the low p values – did not reach statistical significance.
The 10 mg dose of daridorexant showed numerical improvements, across all efficacy measures, of a smaller magnitude than observed on 25 mg, none of which reached statistical significance.
The results of the two large pivotal studies, testing daridorexant at three doses from 10 to 50 mg, now provide a deep understanding of its efficacy and tolerability profile. Furthermore, the similar design of the two Phase 3 studies allows for the two groups of 25 mg and placebo to be pooled and a pre-planned analysis to be made. This pooled analysis will further characterize the effect of daridorexant.
Guy Braunstein, MD and Head of Global Clinical Development of Idorsia, commented:
“I want to start with a thank you to the study participants, investigators and their support staff, and the Idorsia team for delivering another comprehensive set of robust data. I am delighted to see the replicated effect of 25 mg of daridorexant in this large confirmatory study. The consistency of the treatment effect across both studies is remarkable. I believe the fact that daridorexant improves daytime functioning is a real breakthrough for patients. I am looking forward to the integration of all aspects of the program, including the pooled data, the long-term extension data, the clinical pharmacology program, and all that we can learn from the patient reported outcome instruments. There is a lot of work for us to do as we interact with the health authorities and share the data with the scientific community.”
Source: Company Press Release