Effectiveness and Safety of Lemborexant Over 12 Months in Adults with Insomnia Disorder: Longterm Results From the Phase 3 SUNRISE-2 Study (420)

Objective: Assess long-term effectiveness/safety of lemborexant (LEM), a dual orexin receptor antagonist in development for insomnia disorder. Background: In SUNRISE-2 (NCT02952820; E2006-G000-303), LEM demonstrated significant benefit versus placebo on patient-reported (subjective) sleep onset and maintenance over 6 months (M6). Here we report long-term (12 months) LEM effectiveness and safety. Design/Methods: SUNRISE-2 was a randomized, double-blind, placebo-controlled (first 6 months [Period 1]), 12-month global phase 3 study in adults age ≥18y with insomnia disorder. Period 1: subjects randomized to placebo or LEM (5mg, [LEM5]; 10mg, [LEM10]). Period 2: placebo subjects rerandomized to LEM5 or LEM10 (results not reported here); LEM subjects continued their assigned dose. Changes from baseline were assessed from sleep diary data. P -values at M6 were based on mixed-effect repeated measurement analysis evaluating least squares mean treatment differences for placebo versus LEM. Results: The Full Analysis Set comprised 949 subjects (Period 1: Placebo, n=318; LEM5, n=316; LEM10, n=315). At the end of Period 1/M6, 251 and 226 subjects continued LEM5 and LEM10, respectively. Median subjective sleep onset latency (min) was significantly reduced with LEM5 (−21.8) and LEM10 (−28.2) versus placebo (−11.4; both P <0.0001) at M6; reductions persisted at Month 12 (M12; LEM5, −25.7; LEM10, −32.9). Mean (SD) increases in subjective sleep efficiency (%) were significantly greater with LEM5 (15.3 [14.6]) and LEM10 (15.6 [15.6]) versus placebo (10.4 [13.8]; both P ≤0.0001) at M6; increases persisted at M12 (LEM5, 15.8 [14.3]; LEM10, 17.6 [15.9]). Mean (SD) decreases in subjective wake after sleep onset (min) were significantly greater with LEM5 (−51.5 [67.3]) and LEM10 (−48.1 [68.6]) versus placebo (−32.1 [55.3], both P <0.05) at M6; decreases persisted at M12 (LEM5, −53.4 [61.5]; LEM10, −56.8 [70.6]). Most treatment-emergent adverse events were mild/moderate. No deaths occurred. Conclusions: LEM was well tolerated and effective over 12 months, supporting LEM as a potential long-term treatment option for insomnia disorder. Disclosure: Dr. Yardley has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Ltd. Dr. Karppa has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amgen, Eisai Inc., Teva Pharmaceuticals. Dr. Inoue has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai, Alfresa Pharma, MSD, and Takeda Pharmaceutical. Dr. Inoue has received research support from Eisai, Takeda Pharmaceutical, Philips, Koike Medical, Astellas Pharma, and Janssen Pharmaceutical.Dr. Pinner has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Ltd. Dr. Perdomo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Inc. Dr. Filippov has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities as an employee of Eisai Inc. Dr. Kubota has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Co. Ltd. Dr. Moline has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Inc.