AN OPEN-LABEL, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF TREATMENT WITH LEMBOREXANT IN SUBJECTS WITH CHRONIC INSOMNIA (SOMNUS STUDY)

Abstract Background Effective alternative therapies are needed to improve outcomes in the treatment of insomnia disorder due to concerns regarding the risks of tolerance, dependence, falls and withdrawal syndrome with the use of pharmacological treatments such as benzodiazepine-receptor agonists (BZRA). Lemborexant (LEM), a competitive dual orexin-receptor antagonist approved in Japan and other countries to treat adults with insomnia, has shown superior therapeutic efficacy to zolpidem extended-release 6.25 mg in a phase 3 clinical trial; therefore, LEM may be a potential alternative candidate. Aims & Objectives To evaluate whether the approach of a direct transition to LEM either from a Z-drug (zolpidem, zopiclone, or eszopiclone) or suvorexant (SUV) monotherapy or from SUV or BZRA and ramelteon (RMT) combination therapy can be supported for patients with insomnia. Methods A prospective, nonrandomized, open-label, multicenter study conducted in Japan with 90 subjects with chronic insomnia dissatisfied with current treatment was designed to investigate whether direct transition to LEM improved patient satisfaction. The study was comprised of four cohorts: (1) nonbenzodiazepine sedative-hypnotic (Z-drug) monotherapy, (2) orexin receptor antagonist (SUV) monotherapy, (3) SUV plus BZRA combination therapy, and (4) melatonin receptor agonist (RMT) plus BZRA combination therapy. The primary outcomes were continuation of treatment after 2 weeks (end of titration phase) and 14 weeks (titration phase and maintenance phase), as well as responses on the Patient Global Impression – Insomnia version (PGI-I) and Insomnia Severity Index (ISI) scales. Subjects in the BZRA combination therapy groups could attempt, but were not required, to decrease BZRA use during the maintenance phase. This study was approved by the Certified Clinical Research Review Board, and informed consent was obtained. Results In all, 95.6% (n=86/90) successfully transitioned to LEM after 2 weeks, and LEM continuation rates were 97.8% (n=88/90) at the completion of the titration phase and 82.2% (n=74/90) at the completion of the maintenance phases. At 14 weeks, dose reduction and interruption of BZRA occurred in 12.5% (n=4/32) of the combined cohort. In the entire cohort, PGI-I scores showed a greater percentage of positive responses than negative responses. ISI total scores also improved over time after the transition to LEM. The overall incidence of adverse events was 47.8% (n=43/90) and none were serious. Discussion & Conclusion These findings suggest that direct transition to LEM is a valid treatment option for insomnia in patients who are dissatisfied with their current treatment. Support Eisai, Ltd.