Consistency of objective and subjective evidence for the efficacy of lemborexant

To review the efficacy of lemborexant (LEM), a dual orexin-receptor antagonist approved in multiple countries for treatment of insomnia in adults, by assessing the consistency of the available LEM objective and subjective evidence.

Data from 2 pivotal phase 3, randomized, double-blind, parallel-group, placebo (PBO)-controlled studies are reviewed. Study 304 (1-month) and Study 303 (12-months; only first 6 months included here) evaluated the efficacy/safety of LEM 5 mg (LEM5) and LEM 10 mg (LEM10) in adults with insomnia disorder. Objective sleep onset (latency to persistent sleep [LPS]) and sleep maintenance (wake after sleep onset [WASO] and total sleep time [TST]) were assessed with polysomnography in Study 304. Subjective sleep onset latency (sSOL) and sleep maintenance (sWASO and sTST) were assessed with sleep diaries in both studies. Other patient-reported efficacy measures included Insomnia Severity Index-total score (ISI-TS), ISI-daytime functioning (ISI-DF), Fatigue Severity Scale (FSS), and Patient Global Impression-Insomnia (PGI-I).

Compared with PBO, significantly larger decreases (improvements) from baseline in LPS, sSOL, WASO, and sWASO and significantly larger increases (improvements) from baseline in TST and sTST were observed within the first week of LEM treatment (as early as within the first 1-2 nights) and were sustained throughout the treatment period (1-6 months) (all p < 0.05, except for sWASO at Month 1). These improvements aligned with significantly larger decreases (improvements) from baseline in ISI-TS, ISI-DF, and PGI-I (all p < 0.05). Significantly larger decreases (improvement) from baseline in FSS scores were observed at 3 and 6 months (both p < 0.05).

LEM showed concordance in its ability to improve objective and subjective measures of nighttime sleep, as well as daytime functioning and patient perception of nighttime sleep. These findings demonstrate that LEM is effective both objectively and from the patient's perspective, supporting LEM as a valuable treatment option for adults with insomnia.