Examine the effects of lemborexant (LEM) on patient-reported insomnia disease severity using the Insomnia Severity Index (ISI) and on fatigue using the Fatigue Severity Score (FSS) over 12 months.

LEM is a dual orexin receptor antagonist in development for the treatment of insomnia. In the Phase 3 study SUNRISE-2 (NCT02952820; E2006-G000-303), LEM provided significant benefit on sleep onset and maintenance versus placebo over 6 months.

Subjects (n=949, full analysis set) were randomized to placebo or LEM (5mg [LEM5]; 10mg [LEM10]) for 6 months (Treatment Period 1: Placebo, n=318; LEM5, n=316; LEM10, n=315). In Treatment Period 2, placebo subjects were rerandomized to LEM5 or LEM10 (not included in analysis); subjects on LEM continued at the same dose for another 6 months (251 for LEM5; 226 for LEM10). Changes from baseline in ISI total score (TS) and FSS-TS at Month 6 (M6) were analyzed using a mixed-effect model repeated measurement analysis, adjusted for relevant factors with baseline score as a covariate. P-values were based on the least squares mean (LSM) treatment difference for either dose of LEM versus placebo.

Baseline mean ISI-TS and FSS-TS were similar across groups. LSM (SE) decreases (improvement) from baseline in ISI-TS were significantly greater for LEM5 (−9.5 [0.4]) and LEM10 (−9.7 [0.4] versus placebo (−7.4 [0.4]; both P<0.0001) at M6. Decreases (mean [SD]) were observed also at Month 12 (M12; LEM5, −11.5 [6.2]; LEM10, −11.2 [6.2]). LSM (SE) decreases from baseline (improvement) at M6 in FSS-TS were also significantly greater for LEM5 (−8.9 [0.8]) and LEM10 (−9.0 [0.8]) versus placebo (−6.4 [0.8]; both P<0.05). Decreases (mean [SD]) were also observed at M12 (LEM5, −13.3 [14.4]; LEM10, −11.0 [15.6]). LEM was well tolerated, with most treatment–emergent adverse events mild to moderate in severity.

LEM5 and LEM10 reduced subject-reported disease severity and fatigue over 12 months.