Lemborexant for insomnia

Laboratory PSG monitoring was performed for 2 consecutive nights at baseline (before treatment), the first 2 treatment nights, and the final 2 treatment nights (Nights 29 and 30). The primary study endpoint was the change in latency to persistent sleep (LPS) from baseline to the final 2 nights for the lemborexant doses compared with placebo. Additional PSG-based endpoints were similar comparisons for sleep efficiency (percent time asleep during the 8-hour laboratory recording period) and objective wake after sleep onset (WASO) compared with placebo, and WASO during the second half of the night (WASO2H) compared with zolpidem. Patients completed Insomnia Severity Index (ISI) questionnaires at baseline and the end of the treatment to compare disease severity. Subjective assessments were done daily with electronic diary entries that included sleep onset latency (sSOL), sWASO, and subjective sleep efficiency.

In comparison with placebo, both lemborexant doses were associated with significantly improved PSG measures of LPS, WASO, and sleep efficiency during nights 1 and 2 that were maintained through Nights 29 and 30 (Table 2^1,9). The lemborexant doses also demonstrated significant improvements in WASO2H compared with zolpidem and placebo on the first 2 and final 2 treatment nights. Analyses of the subjective assessments (sSOL, sWASO, and sleep efficiency) compared the baseline with means for the first and the last treatment weeks. At both lemborexant doses, the sSOL was significantly reduced during the first and last weeks compared with placebo and zolpidem. Subjective sleep efficiency was significantly improved at both time points for the lemborexant doses, though these were not significantly different from the zolpidem values. The sWASO values were significantly decreased for both lemborexant doses at both time points compared with placebo. During the first treatment week, both lemborexant doses did not differ significantly from zolpidem in the sWASO change from baseline; however, at the final treatment week, the zolpidem value was significantly improved compared with lemborexant, 5 mg, but not significantly different from lemborexant, 10 mg. The ISI change from baseline to the end of the treatment period showed significant improvement for the lemborexant doses and zolpidem extended-release compared with placebo.

In the Sunrise 2 study, patients who met the criteria for insomnia disorder (age range 18 to 88, mean 55; 68% female) were randomized to groups taking nightly doses of lemborexant, 5 mg (n = 323), lemborexant, 10 mg (n = 323), or placebo (n = 325) for 6 months.¹⁰ Inclusion criteria required an sSOL of at least 30 minutes and/or a sWASO of at least 60 minutes 3 times a week or more during the previous 4 weeks. Efficacy was assessed with daily electronic diary entries, with analyses of change from baseline for sSOL (primary endpoint, baseline to end of 6-month study period), sWASO, and patient-reported sleep efficiency (sSEF). Subjective total sleep time (sTST) represented the estimated time asleep during the time in bed. Additional diary assessments related to sleep quality and morning alertness. All of these subjective assessments were compared as 7-day means for the first week of treatment and the last week of each treatment month.

The superiority of lemborexant, 5 mg and 10 mg, compared with placebo was demonstrated by significant improvements in sSOL, sSEF, sWASO, and sTST during the initial week of the treatment period that remained significant at the end of the 6-month placebo-controlled period (Table 3^1,10). At the end of 6 months, there were significantly more sleep-onset responders and sleep-maintenance responders among patients taking lemborexant compared with those taking placebo. Sleep-onset responders were patients with a baseline sSOL >30 minutes and a mean sSOL ≤20 minutes at the end of the study. Sleep-maintenance responders were participants with a baseline sWASO >60 minutes who at the end of the study had a mean sWASO ≤60 minutes that included a reduction of at least 10 minutes.

Following the 6-month placebo-controlled treatment period, the Sunrise 2 study continued for an additional 6 months of nightly active treatment for continued safety and efficacy assessment. Patients assigned to lemborexant, 5 mg or 10 mg, during the initial period continued on those doses. Those in the placebo group were randomized to either of the 2 lemborexant doses.

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