LAUSR

The Insomnia Severity Index (ISI) is a 7-item self-reported questionnaire evaluating perception of symptom severity included in Phase 3 studies of lemborexant (LEM), a competitive dual orexin receptor antagonist approved in several countries to treat adults with insomnia. The ISI total score, and items 4-7 for daytime function (DF), improved significantly with LEM treatment compared to placebo (PBO) as assessed at 1, 3 and 6 months. Here we report shifts in DF scores at 6 months depending on baseline severity. Study 303 was a 12-month, randomized, double-blind PBO-controlled (first 6months; Treatment Period 1 [TP1]) phase 3 study in subjects (age ≥18y) with insomnia disorder. Subjects were randomized to PBO, LEM 5mg (LEM5) or 10mg (LEM10) for 6 months. ISI items are rated on a 5-point Likert scale from 0 (no problem) to 4 (very severe problem). Daytime-related items include ratings on sleep satisfaction, extent symptoms are noticeable to others, cause worry/distress, or interferes with daily function. Data were analyzed by Cochran-Mantel-Haenszel test of general association vs placebo. Of the 949 subjects, 749 (78.9%) completed the ISI at baseline and end of TP1: PBO (258/318 [81.1%]; LEM5, 257/316 [81.3%]; LEM10, 234/315 [74.3%]). Baseline daytime ISI-total-score distribution was similar between groups; most had scores of 9-12 (66.7-68.6%). At the end of TP1, more subjects with baseline scores of 9-12 shifted to 0-4 with LEM5 (49.7%) and LEM10 (46.2%) than with PBO (26.6%). Similarly, more subjects with baseline scores of 13-16 shifted to 0-4 with LEM5 (39.1%) and LEM10 (46.3%) than with PBO (29.6%). An additional 28.1% and 25.9% of subjects with LEM5 or LEM10, respectively, with baseline scores of 13-16 shifted to scores of 9-12, compared with 31.5% of PBO. The overall shift distributions were significantly different, favoring both LEM groups (p< 0.01). More LEM-treated subjects improved in daytime functioning as evidenced by the significantly large number of subjects whose scores moved into the lower categories (i.e., better sleep) compared with PBO subjects. These data support important improvements in daytime function that are evident even after 6 months of continuous LEM treatment. Eisai Inc.