Efficacy and safety of lemborexant over 12 months in Asian adults with insomnia disorder

Amitabh Dash, Kate Pinner, Yuichi Inoue, Kenichi Hayashida, Sung Chul Lim, Chang-Ho Yun, Tsuo-Hung Lan, Chieh-Liang Huang, Jane Yardley, Naoki Kubota, Margaret Moline, Amitabh Dash, Kate Pinner, Yuichi Inoue, Kenichi Hayashida, Sung Chul Lim, Chang-Ho Yun, Tsuo-Hung Lan, Chieh-Liang Huang, Jane Yardley, Naoki Kubota, Margaret Moline

Abstract

Study objectives: Lemborexant (LEM) is a dual orexin receptor antagonist approved for treating adults with insomnia. We analyzed the efficacy (subjective sleep outcomes) and safety of LEM over 12 months in the subgroup of Asian subjects from Study E2006-G000-303 (Study 303).

Methods: Study 303 was a 12-month, randomized, placebo-controlled (first 6 months), double-blind, parallel-group, phase 3 study of adults with insomnia disorder. During the 6-month Period 1, subjects were randomized (1:1:1) to placebo, LEM 5 mg (LEM5), or LEM 10 mg (LEM10); LEM subjects continued treatment in the following 6-month Period 2. Outcome measures included subject-reported (subjective) sleep onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), total sleep time (sTST), Insomnia Severity Index (ISI), and Patient Global Impression-Insomnia version (PGI-I). Treatment-emergent adverse events (TEAEs) were assessed.

Results: Overall, 178 Asian subjects (Japanese, n = 161; Chinese, n = 4; other Asian, n = 13) were included. Greater decreases in sSOL and sWASO and increases in sSE and sTST from baseline were observed with LEM vs placebo at 6 months; LEM benefits were sustained through 12 months. Greater decreases in ISI total score were seen with LEM vs placebo at 6 months; improvements from baseline with LEM continued through 12 months. For each PGI-I item, LEM-treated subjects had more positive medication effects than placebo-treated subjects at 6 months; these effects were maintained with LEM in Period 2. TEAEs were generally mild to moderate.

Conclusions: LEM improved subjective sleep parameters and was well-tolerated in Asian subjects with insomnia disorder over 12 months.

Clinical trial registration: ClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39.

Keywords: Asian continental ancestry group; Dual orexin receptor antagonist; Hypnotics and sedatives; Insomnia disorder; Lemborexant; Treatment efficacy.

Conflict of interest statement

Financial disclosure: AD is an employee of Eisai Singapore Pte Ltd. KP and JY are employees of Eisai Ltd. YI has received grants and/or personal fees from Eisai Inc., Eisai Ltd., Merck Sharp & Dohme, and Takeda in relation to the submitted work; has received grants or personal fees from Alfresa Pharma, Philips, and Koike Medical; and has received funding for clinical trials from Astellas and Janssen outside of the submitted work. KH has received grants/personal fees and consultant/speaker fees from Eisai Inc.; has received funding for clinical trials from Eisai Inc.; and has received personal fees from and Eisai Ltd., and Merck Sharp & Dohme. SCL has received grants/personal fees from Eisai Inc. CHY has no conflict of interests relevant to this study. THL and CLH have received funding for clinical trials from Eisai Inc. and have no conflicts of interests relevant to this study. NK is an employee of Eisai Co., Ltd. MM is an employee of Eisai Inc.; she has been issued a patent and has pending and planned patents broadly related to this work. Nonfinancial disclosure: None. The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: https://doi.org/10.1016/j.sleepx.2022.100044.

© 2022 The Authors.

Figures

Fig. 1
Fig. 1
Study design. In the Asian subgroup analysis, Period 2 findings are reported for subjects who received lemborexant (LEM) continuously for 12 months (subjects rerandomized from placebo [PBO] were not included in these analyses). EOS, end of study; LEM5, LEM 5 mg; LEM10, LEM 10 mg; SCR, screening. Reproduced from Yardley J et al. [15] Sleep Med. 2021;80:333–342. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Fig. 2
Fig. 2
Change from baseline in subjective sleep parameters over 12 months in the Asian subgroup for (A) subjective sleep onset latency (sSOL), (B) subjective sleep efficiency (sSE), (C) subjective wake after sleep onset (sWASO), and (D) subjective total sleep time (sTST). sSOL values were log transformed. LEM5, lemborexant 5 mg; LEM10, lemborexant 10 mg; PBO, placebo; SD, standard deviation.
Fig. 3
Fig. 3
Change from baseline in total Insomnia Severity Index (ISI) score over 12 months for the Asian subgroup. LEM5, lemborexant 5 mg; LEM10, lemborexant 10 mg; PBO, placebo; SD, standard deviation.
Fig. 4
Fig. 4
Percentage of subjects reporting each response for Patient Global Impression–Insomnia scale items (A) “medication helped me sleep,” (B) “shortened time to fall asleep,” (C) “increased total sleep time,” and (D) “appropriateness of medication strength,” over 12 months in the Asian subgroup. Percentages are based on the total number of subjects with nonmissing values in the relevant treatment group. LEM5, lemborexant 5 mg; LEM10, lemborexant 10 mg; PBO, placebo.

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