Improvements in Daytime Functioning With Lemborexant Treatment

This work was sponsored by Eisai Inc. Introduction: Daytime impairment is a component of insomnia disorder, which is evaluated by items 4-7 of the 7-item Insomnia Severity Index (ISI). In Study 303 (NCT02952820), lemborexant (LEM), a competitive dual orexin receptor antagonist approved to treat adults with insomnia, led to significant improvement in ISI total score and daytime-function-specific items 4-7 (DF) versus placebo (PBO) at 1, 3, and 6 months (6mo). We report shifts in DF scores over 6mo, based on baseline severity. Methods: Study 303 was a 12-month, randomized, double-blind PBO-controlled (first 6mo) phase 3 study in adults with insomnia disorder. Subjects received PBO, LEM 5mg (LEM5) or 10mg (LEM10) for 6mo. ISI items 4-7 were rated 0 (no problem) to 4 (very severe problem). DF include sleep satisfaction and extent of symptoms noticeable to others, cause worry/distress, or interfere with daily function. Data were analyzed for general association and compared improvement versus staying the same or worsening within baseline subgroups (DF score: 5-8, mild-to-moderate; 9-12, moderate-to-severe; or 13-16, severe-to-very severe). Results: Of 949 subjects, 749 (78.9%) completed the ISI at baseline and 6mo: PBO, n=258/318(81.1%); LEM5, n=257/316(81.3%); LEM10, n=234/315(74.3%). At 6mo, more subjects with baseline scores 13-16 and 9-12 shifted to 0-4 with LEM5 (13-16: 39.1%, P=0.23; 9-12: 49.7%, P=0.01) and LEM10 (13-16: 46.3%, P=0.01; 9-12: 46.2%, P=0.08) versus PBO (13-16: 29.6%; 9-12: 26.6%). Overall, shifts towards improvement in DF scores favored both LEM groups (P