Idorsia announced positive results for the comprehensive Phase 2 program with the dual orexin receptor antagonist ACT-541468 (DORA) in insomnia, with zolpidem as an active reference. The program comprised two placebo-controlled dose-response studies to evaluate the safety and efficacy of ACT-541468 in adult and elderly patients with insomnia, with a total of 418 patients participating in the trials.
Martine Clozel, MD and Chief Scientific Officer of Idorsia, commented: “Our scientists have been true pioneers in the field of orexin antagonism. More than 20000 compounds were synthesized and studied before ACT-541468 was selected. Its discovery is the result of an extensive effort to combine two important characteristics of a sleep medication: maintaining efficacy throughout the night, and a low potential for a next-day residual effect. I am delighted to see that the positive readouts from this comprehensive Phase 2 program are consistent with our preclinical predictive models, for both adult and elderly patients with insomnia.”
The first study in 360 adults (ranging from 18 to 64 years) with a treatment duration of 4 weeks showed a significant dose-dependent decrease in WASO at Day 1 & 2 (average decrease of wake time after sleep onset from baseline on the first 2 nights of treatment, measured by polysomnography). In addition, ACT-541468 significantly decreased LPS (latency to persistent sleep) in a dose-dependent manner.
Treatment with ACT-541468 was generally well tolerated. There were no reports of serious adverse events related to ACT-541468.
The positive readouts of a second study, conducted in 58 elderly patients (ranging from 65 to 85 years), confirmed the efficacy and safety profile of ACT-541468 in this population. The results of this study also showed a significant decrease in WASO and LPS at Day 1 & 2 in a dose-dependent manner.
The overall results of the Phase 2 program with ACT-541468 in insomnia support the decision to initiate efficacy and safety confirmatory studies in both adult and elderly patients.
Detailed results of the Phase 2 program will be made available through scientific disclosure at upcoming congresses and in peer-reviewed publications.
Guy Braunstein, MD and Head of Global Clinical Development of Idorsia, commented: “The positive results of the Phase 2 program demonstrate that our DORA can deliver on the potential its mechanism of action offers in insomnia. We have observed a fast onset of sleep and a duration of action which does not exceed a normal night’s sleep. We will now consult with health authorities and progress this important asset into the Phase 3 program as quickly as possible.”
Jean-Paul Clozel, MD and Chief Executive Officer of Idorsia, commented: “We couldn’t have asked for a better start for Idorsia. First the excellent results with aprocitentan, where we are in discussions with health authorities to move into Phase 3 for development in resistant hypertension, and now our dual orexin receptor antagonist moving into Phase 3 for insomnia. This will take us an important step closer to delivering on one of our major strategic objectives – to bring at least three products to market within the next 5 years that have the potential to substantially change the treatment options in their target disease.”
Filed Under: Drug Discovery