TRANSITIONING BETWEEN DRUG CLASSES: DATA FROM TWO STUDIES WITH LEMBOREXANT AND Z-DRUGS

Abstract Background While switching of medications for insomnia occurs frequently in clinical practice, few clinical studies have examined the impact of transitioning patients between different insomnia medications, especially between different classes of drugs (eg, GABA-ergic agonists versus dual-orexin- receptor-antagonists [DORA]). Lemborexant (LEM) is a DORA approved in the United States and Japan with the same dosing instructions to treat adults with insomnia. Two studies (United States: E2006- A001-312, Study 312, NCT04009577; Japan: E2006-M081-401, Study 401, NCT04742699) evaluated the success rate of transitioning to LEM in subjects with insomnia who were dissatisfied with their previous insomnia medications in terms of efficacy or tolerability. In Japan, the focus was particularly on those who wished to switch from all or some of their previous insomnia medications to LEM. Aims & Objectives Evaluate the success rate of direct transitioning from non-benzodiazepine GABA- ergic agonist Z-drugs to LEM in subjects with insomnia who were dissatisfied with their current treatment in terms of effectiveness and/or tolerability. Methods Both studies employed an open-label design that examined prespecified dosing paradigms for directly transitioning subjects from a Z-drug to LEM without a down-titration of the Z-drug. Study 312 included a 3-week Screening Period (subjects continued zolpidem [ZOL]), 2-week Titration Period (TITR), 12-week Extension Period (EXT; not reported here), and 4-week Follow-up Period. Adults with insomnia who were intermittent (3-4 nights/week) or frequent (at least 5 nights/week) ZOL users were assigned to 1 of 2 cohorts. Cohort 1: Intermittent ZOL users and subjects with 1 week each of intermittent and frequent ZOL usage began TITR with LEM 5 mg (LEM5). Cohort 2: Frequent ZOL users were randomized 1:1 to LEM5 or LEM 10 mg (LEM10). Subjects who successfully transitioned (elected to continue LEM in EXT or to discontinue for reasons other than AE or lack of efficacy) to LEM had the option to enter the EXT. Study 401 was of similar design, with the exception of a 2-week Screening Period during which subjects continued their current Z-drug (ZOL, zopiclone, or eszopiclone); all subjects started with LEM5. The primary endpoint in both studies was the proportion of subjects who successfully transitioned to LEM at the end of TITR. Routine safety evaluations were conducted. Results In Study 312, the Full Analysis Set comprised 53 subjects (Cohort 1, n=10; Cohort 2, n=43). Following 2 weeks of LEM treatment, the majority of subjects (overall, n=43/53; 81.1%) transitioned from ZOL to LEM, regardless of prior intermittent or frequent use of ZOL determined during the Screening Period. In Study 401, 25 subjects were taking Z-drugs (n=6 ZOL, n=1 zopiclone, n=18 eszopiclone) during TITR. The proportion of subjects with successful LEM treatment in the Z-drug group was 92.0% (n=23/25). No new safety signals emerged during transitioning, and the safety profile was similar to pivotal trials. Discussion & Conclusion Results from both studies indicate that adults can successfully transition directly from a Z-drug to LEM. LEM was generally well tolerated. Support Eisai Inc; Eisai Co., Ltd.