This study examined the effects of lemborexant (LEM) compared with placebo (PBO) on subject-reported insomnia disease severity, assessed by the Insomnia Severity Index (ISI), and fatigue, assessed by the Fatigue Severity Score (FSS), from the 6-month PBO-controlled period of SUNRISE-2.

SUNRISE-2 (NCT02952820; E2006-G000-303) was a 12-month randomized, double-blind, PBO-controlled (first 6-months) Phase 3 study. After an ~2-week PBO run-in, subjects were randomized to PBO, LEM 5mg (LEM5) or LEM 10mg (LEM10) for 6 months. The ISI and the FSS were administered at baseline [BL] and at the end of Months 1, 3, and 6. The ISI daytime functioning score (DFS), based on the ISI items that assess the impact of insomnia symptoms specific to daily functioning (items 4-7), was also evaluated. Mean changes from BL in ISI total score (ISI TS), ISI DFS, and FSS total score (FSS TS) were analyzed using a mixed-effect model repeated measurement analysis, adjusted for relevant factors and BL score (ISI TS, ISI DFS, or FSS TS) as a covariate.

949 subjects (PBO, n=318; LEM5, n=316; LEM10, n=315) were included in the full analysis set. Median age was 55y (range 18-88y). Mean ISI TS at BL for PBO, LEM5, and LEM10 was 19.0, 19.6 and 19.1, respectively. While mean ISI TS decreased (improved) from BL for all groups, decreases were significantly larger for both LEM5 and LEM10 vs PBO at Month 1 (least squares mean treatment difference [LSM TD]: LEM5, −1.5 [P=0.001]; LEM10, −1.9 [P<0.0001]), Month 3 (LSM TD: LEM5, −2.0; LEM10, −2.6 [both P<0.0001]), and Month 6 (LSM TD: LEM5, −2.1; LEM10, −2.4 [both P<0.0001]). Decreases from BL in mean ISI DFS were also significantly larger for LEM5 and LEM10 vs PBO at Month 1 (LSM TD: LEM5, −0.7 [P=0.014]; LEM10, −0.9 [P=0.001]), Month 3 (LSM TD: LEM5, −1.2 [P=0.0001]; LEM10, −1.4 [P<0.0001]), and Month 6 (LSM TD: LEM5, −1.3; LEM10, −1.3 [both P<0.0001]).

Mean FSS TS at BL was 35.2, 37.4, and 36.0 for PBO, LEM5, and LEM10, respectively. Mean FSS TS decreased (improved) from BL in all groups at the end of Month 1 (decreases were larger and significant for LEM10 vs PBO [LSM TD: –2.0 (P=0.026)]), and Month 3 (decreases were larger and significant for LEM5 [LSM TD: –2.2 (P=0.021)] and LEM10 [LSM TD: –3.0; (P=0.001)] vs PBO). At Month 6, mean FSS TS remained improved from BL in all treatment groups (PBO, –6.3; LEM5, –10.1; and LEM10, –8.9). These decreases were larger and significant for LEM5 (LSM TD: –2.5 [P=0.013]) and LEM10 (LSM TD: –2.6 [P=0.013]) vs PBO. LEM was well tolerated with most adverse events mild to moderate in severity.

In SUNRISE-2, LEM5 and LEM10 significantly reduced subject-reported disease severity and fatigue vs PBO after 6 months of treatment. Reduced severity in insomnia symptoms with LEM5 and LEM10 also translated to improved daytime functioning.

Supported by Eisai Inc.

The dual orexin receptor antagonist, lemborexant (LEM), is being investigated for the treatment of insomnia disorder. Drugs targeting the orexin system, like LEM, may decrease wakefulness and promote sleep with fewer potential adverse effects (AEs) than some currently available pharmacological insomnia therapies. LEM has been studied in 2 pivotal phase 3 trials for insomnia disorder, SUNRISE-1 (NCT02783729; E2006-G000-304) and SUNRISE-2 (NCT02952820; E2006-G000-303). Analyses presented here are derived from patient-reported (subjective) efficacy data pooled from SUNRISE-1 and SUNRISE-2 during 1-month of treatment in adult and elderly (age ≥65y) subjects with DSM-5 insomnia disorder.

SUNRISE-1 was a 1-month, double-blind, randomized, placebo (PBO)- and active-controlled (zolpidem tartrate extended-release 6.25mg [ZOL; not reported), parallel-group study in 1006 subjects (age ≥55y). SUNRISE-2 was a 12-month (6-month PBO-controlled, 6-month active treatment), double-blind study in 949 subjects (age ≥18y). In both studies, subjects were randomized to PBO, LEM5, or LEM10 (SUNRISE-1 subjects could also be randomized to ZOL; not included in pooled analysis) following a 2-week PBO run-in. Changes from baseline (BL) in subjective sleep onset latency (sSOL), subjective sleep efficiency (sSE), and subjective wake after sleep onset (sWASO) were analyzed using mixed effect model repeated measurement analysis. Sleep onset and sleep maintenance responders were analyzed via Cochran–Mantel–Haenszel test stratified by study, region and age group.

The pooled analysis set comprised 1693 subjects (PBO, n=527; LEM5, n=582; LEM10, n=584). Reductions from BL in sSOL were significantly greater for LEM5 and LEM10 vs PBO during the first 7 days of treatment and at the end of Month 1 (all comparisons P<0.0001). Both doses of LEM significantly increased sSE from BL (P<0.001 both time points) more than PBO and reduced sWASO from BL (P<0.0001 first 7 days [both doses]; P<0.05 [LEM5] and P<0.001 [LEM10] at Month 1) more than PBO. After the first 7 days and at the end of Month 1, the proportion of sSOL responders (≤20 min if BL >30 min) was statistically significantly larger for LEM5 and LEM10 vs PBO (first 7 days: both P<0.0001; last 7 days of Month 1: both P<0.001) and the proportion of sWASO responders (≤60 minutes and a reduction from BL by >10 min, if BL >60 min) was statistically significantly larger for LEM5 and LEM10 vs PBO (first 7 days: both P<0.01; last 7 days of Month 1: both P<0.05). LEM was well tolerated. Most AEs were mild to moderate in severity, and rates of severe or serious AEs were low.

LEM improved sleep onset and sleep maintenance in adult and elderly subjects with insomnia disorder, and was well tolerated. Average values on sleep maintenance endpoints showed that subjects treated with LEM obtained >1 hour of additional sleep per night vs subjects who received PBO.

Supported by Eisai Inc.

Early life exposures affect health and disease across the life course and potentially across multiple generations. The Clinical and Translational Research Institutes (CTSIs) offer an opportunity to utilize and link existing databases to conduct lifespan research.

A survey with Lifespan Domain Taskforce expert input was created and distributed to lead lifespan researchers at each of the 64 CTSIs. The survey requested information regarding institutional databases related to early life exposure, child-maternal health, or lifespan research.

Of 64 CTSI, 88% provided information on a total of 130 databases. Approximately 59% (n=76/130) had an associated biorepository. Longitudinal data were available for 72% (n=93/130) of reported databases. Many of the biorepositories (n=44/76; 68%) have standard operating procedures that can be shared with other researchers.

The majority of CTSI databases and biorepositories focusing on child-maternal health and lifespan research could be leveraged for lifespan research, increased generalizability and enhanced multi-institutional research in the United States.