Lemborexant Demonstrates Efficacy in Elders

Margaret Moline, PhD

Data from the phase 3 SUNRISE-2 trial (NCT02952820) presented virtually at SLEEP 2020 revealed that treatment with lemborexant (Dayvigo; Eisai) was well-tolerated and efficacious in elderly subjects aged 65 years and older.¹

SUNRISE-2 was a double-blind, placebo-controlled, 12-month trial that evaluated sleep measures of both 5- and 10-mg doses of lemborexant compared to placebo in multiple patient populations. In total, there were 949 subjects in the full analysis set, with 262 of them being elders.

At 6 months, the median sleep onset latency (sSOL) significantly decreased from baseline for patients treated with lemborexant 5-mg (—21.7 minutes) and lemborexant 10 mg (–26.0 minutes) compared to placebo (–10.8 minutes; P <.0001 and <.01, respectively). Following 12 months of treatment, investigators noted that decreases of sSOL were maintained in the 2 dose groups (lemborexant 5 mg: —29.3 minutes; lemborexant 10 mg: –34.3 minutes).

Lead author Margaret Malone, PhD, international project team lead, Eisai, and colleagues documented that at 6 months, the mean increase from baseline in sleep efficiency (sSE) was significantly larger for those treated with lemborexant 5 mg (16.9 minutes [standard deviation (SD), 13.6]; P <.001) and lemborexant 10 mg (14.9 minutes [SD, 15.9]; P <.01) compared with placebo (8.5 minutes [SD, 13.3]). Patients maintained increases of 18.1 (SD, 12.5) and 18.0 (SD, 16.8) minutes in sSE in the lemborexant 5- and 10-mg groups across the 12-month stretch, respectively.

Wake after sleep onset (sWASO), the third primary sleep end point assessed from sleep diaries was also significantly impacted by those treated with lemborexant. At 6 months, investigators saw a significant decrease in the mean change of sWASO in the lemborexant 5-mg (—54.8 minutes [SD, 64.4]; P <.01) and 10-mg groups (—51.4 minutes [SD, 69.3]; P <.05) compared to placebo (—26.5 minutes [SD, 52.9]). The mean decrease in sWASO was maintained for those who received lemborexant 5 mg (–58.6 [SD, 46.0]) and 10 mg (–60.9 [SD, 80.4]) at the end of the 12-month trial.

Along with increases in sleep outcomes, lemborexant was shown to be well-tolerated. The most common treatment emergent adverse events (TEAEs), occurring in ≥10% of either the 5- or 10-mg groups, respectively, were somnolence (9.3% and 19.0%), nasopharyngitis (9.3% and 10.7%) and headache (10.5% and 6.0%).

Moline and colleagues also published additional data from SUNRISE-2 at SLEEP 2020 which demonstrated improvements in sleep outcomes in those who were originally administered placebo, but then rerandomized to lemborexant for the remaining 6 months of the trial.²

The subset of patients within that trial showed benefit from the drug as early as 1 month after treatment initiation and found the drug to be well-tolerated. Additionally, the treatment showed significant impact on measures such as sSOL, sSE, and sWASO. The AEs were consistent with those seen in the initial 6 months of treatment for patients originally randomized to lemborexant.

The drug was FDA approved in December 2019 in both the 5- and 10-mg doses. Lemborexant, a small molecule orexin receptor antagonist, was approved based on both the SUNRISE-1 and SUNRISE-2 studies, and in June 2020, Eisai announced its commercial availability.^3,4

REFERENCES

1. Moline M, Inoue Y, Pinner K, et al. Long-term efficacy and safety of lemborexant in elderly adults with insomnia disorder: results from SUNRISE-2. Presented virtually at SLEEP 2020. Poster 0474.

2. Yardley J, Inoue Y, Pinner K, et al. Effectiveness and safety of lemborexant in subjects previously treated with placebo for 6 months in SUNRISE- Presented virtually at SLEEP 2020. Poster 0473.

3. US FDA approved Eisai’s Dayvigo (lemborexant) for the treatment of insomnia in adult patients [news release]. Woodcliff Lake, NJ: Eisai Inc. December 23, 2019. Accessed August 31, 2020. eisai.mediaroom.com/2019-12-23-U-S-FDA-Approves-Eisais-DAYVIGO-TM-lemborexant-for-the-Treatment-of-Insomnia-in-Adult-Patients.

4. Eisai Announces U.S. Availability of DAYVIGO™ (lemborexant) CIV, a New Treatment Option for Adults With Insomnia [news release]. Woodcliff Lake, NJ: Eisai Inc; Published June 1, 2020. Accessed August 31, 2020. eisai.mediaroom.com/2020-06-01-Eisai-Announces-U-S-Availability-of-DAYVIGO-TM-lemborexant-CIV-a-New-Treatment-Option-for-Adults-With-Insomnia