Assess long-term effectiveness/safety of lemborexant (LEM), a dual orexin receptor antagonist in development for insomnia disorder.

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.

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.

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.

LEM was well tolerated and effective over 12 months, supporting LEM as a potential long-term treatment option for insomnia disorder.