Effect of Lemborexant Treatment Across 12 Months on Fatigue Severity and Sleep Outcomes in Subjects With Clinically Significant Fatigue at Baseline

Introduction: The Fatigue Severity Scale (FSS) assesses impact of fatigue on patients’ lives. Lemborexant (LEM) efficacy was examined in the subgroup of subjects with baseline FSS total score (TS) ≥36 (clinically significant fatigue [CSF]) from Study 303 (SUNRISE-2; NCT02952820).

Methods: Study 303 was a 12mo, randomized, double-blind study in subjects ≥18y with insomnia (n=949). Subjects received placebo or LEM (5mg [LEM5]; 10mg [LEM10]) for 6mo. For second 6mo, placebo subjects were rerandomized to LEM (reported separately); LEM subjects continued assigned dose.

Results: In the CSF subgroup, mean baseline FSS-TS was 45.7, 46.4, and 45.8 for placebo (n=170), LEM5 (n=181), and LEM10 (n=173), respectively. Mean (SD) decreases from baseline in FSS-TS were significantly greater with LEM vs placebo at 6mo (placebo, −11.0[11.7]; LEM5, −15.4[13.9]; LEM10, −15.0[14.2]; both P < 0.05) and sustained at 12mo (LEM5, −20.4[12.8]; LEM10, −17.7[15.0]). Median reductions from baseline in subjective sleep onset latency (min) were greater with LEM vs placebo at 6mo (placebo, −14.3; LEM5, −20.7; LEM10, −25.7) and sustained at 12mo (LEM5, −24.3; LEM10, −27.9). Mean (SD) increases from baseline in subjective sleep efficiency (%) were greater with LEM vs placebo at 6mo (placebo, 11.1[13.3]; LEM5, 16.1[15.6]; LEM10, 14.7[16.2]) and sustained at 12mo (LEM5, 16.2[14.3]; LEM10, 16.9[15.9]). Mean (SD) decreases from baseline in subjective wake after sleep onset (min) at 6mo were also greater (placebo, −31.9[57.6]; LEM5, −59.2[73.2]; LEM10, −48.1[70.2]) and sustained at 12mo (LEM5, −57.5[62.9]; LEM10, −60.4[72.0]).

Conclusion: In this subgroup, LEM benefit on fatigue severity and sleep parameters was observed at 6mo and persisted through 12mo.