164 Pooled Analyses of Patient-Reported Sleep Onset and Maintenance from Two Phase 3 Studies of Lemborexant

Abstract

The dual orexin receptor antagonist, lemborexant (LEM), is being investigated for the treatment of insomnia disorder. Drugs targeting the orexin system, like LEM, may decrease wakefulness and promote sleep with fewer potential adverse effects (AEs) than some currently available pharmacological insomnia therapies. LEM has been studied in 2 pivotal phase 3 trials for insomnia disorder, SUNRISE-1 (NCT02783729; E2006-G000-304) and SUNRISE-2 (NCT02952820; E2006-G000-303). Analyses presented here are derived from patient-reported (subjective) efficacy data pooled from SUNRISE-1 and SUNRISE-2 during 1-month of treatment in adult and elderly (age ≥65y) subjects with DSM-5 insomnia disorder. SUNRISE-1 was a 1-month, double-blind, randomized, placebo (PBO)- and active-controlled (zolpidem tartrate extended-release 6.25mg [ZOL; not reported), parallel-group study in 1006 subjects (age ≥55y). SUNRISE-2 was a 12-month (6-month PBO-controlled, 6-month active treatment), double-blind study in 949 subjects (age ≥18y). In both studies, subjects were randomized to PBO, LEM5, or LEM10 (SUNRISE-1 subjects could also be randomized to ZOL; not included in pooled analysis) following a 2-week PBO run-in. Changes from baseline (BL) in subjective sleep onset latency (sSOL), subjective sleep efficiency (sSE), and subjective wake after sleep onset (sWASO) were analyzed using mixed effect model repeated measurement analysis. Sleep onset and sleep maintenance responders were analyzed via Cochran-Mantel-Haenszel test stratified by study, region and age group. The pooled analysis set comprised 1693 subjects (PBO, n=527; LEM5, n=582; LEM10, n=584). Reductions from BL in sSOL were significantly greater for LEM5 and LEM10 vs PBO during the first 7 days of treatment and at the end of Month 1 (all comparisons P<0.0001). Both doses of LEM significantly increased sSE from BL (P<0.001 both time points) more than PBO and reduced sWASO from BL (P<0.0001 first 7 days [both doses]; P<0.05 [LEM5] and P<0.001 [LEM10] at Month 1) more than PBO. After the first 7 days and at the end of Month 1, the proportion of sSOL responders (≤20 min if BL >30 min) was statistically significantly larger for LEM5 and LEM10 vs PBO (first 7 days: both P<0.0001; last 7 days of Month 1: both P<0.001) and the proportion of sWASO responders (≤60 minutes and a reduction from BL by >10 min, if BL >60 min) was statistically significantly larger for LEM5 and LEM10 vs PBO (first 7 days: both P<0.01; last 7 days of Month 1: both P<0.05). LEM was well tolerated. Most AEs were mild to moderate in severity, and rates of severe or serious AEs were low. LEM improved sleep onset and sleep maintenance in adult and elderly subjects with insomnia disorder, and was well tolerated. Average values on sleep maintenance endpoints showed that subjects treated with LEM obtained >1 hour of additional sleep per night vs subjects who received PBO. Supported by Eisai Inc.