Lemborexant Improves Sleep Outcomes Following Placebo Randomization Switch

Margaret Moline, PhD

Results from the second half of the 12-month, phase 3, SUNRISE-2 trial (NCT02952820) demonstrated improvements in sleep outcomes in those who were originally administered placebo, but rerandomized to lemborexant (Dayvigo; Eisai) for the remaining 6 months of the trial.¹

Presented virtually at SLEEP 2020, August 27—30, patients who switched from placebo to lemborexant 5 mg or 10 mg showed benefit from the drug as early as 1 month after treatment initiation and found the drug to be well-tolerated.

SUNRISE-2 was a double-blind, global, phase 3 study in adults aged 18 years or older with insomnia disorder. Study author Margaret Moline, PhD, international project team lead, Eisai and colleagues randomized subjects to lemborexant 5 mg or 10 mg, or placebo for 6 months. The data released focused on the patients who received placebo who were then rerandomized in the second half of the 12-month study to lemborexant while those already on the drug continued treatment.

At the 6-month baseline, those rerandomized to lemborexant 5 mg (n = 133) and lemborexant 10 mg (n = 125) had a median subjective sleep onset latency (sSOL) of 31.2 and 34.3, respectively. After 1 month, the median sSOL decreased from the 6-month baseline mark by —3.2 and –2.9 in each group, respectively. Six-month results showed decreases of ­–2.7 in the placebo-lemborexant 5-mg group compared to –5.0 in the placebo-lemborexant 10-mg group.

Additionally, the mean subjective sleep efficiency (sSE) increased from the 6-month baseline after 1 month by 3.9 (standard deviation [SD], 12.1) and 3.5 (SD, 8.1) and after 6 months by 3.9 (SD, 13.6) and 4.5 (SD, 13.0) for the 5-mg and 10-mg switch groups, respectively.

Subjective wake after sleep onset (sWASO) scores were decreased after 1 month (placebo-lemborexant 5-mg: —8.5 [SD, 49.4]; placebo-lemborexant 10-mg: –5.7 [SD, 49.4]) and 6 months (placebo-lemborexant 5-mg: –8.2 [SD, 49.0]; placebo-lemborexant 10-mg: –10.0 [SD, 58.8]).

In total, treatment-emergent adverse events (TEAEs) occurred in 54.9% and 57.7% of patients in the placebo-lemborexant 5-mg and 10-mg groups, respectively, similar to the original placebo group, which had a 62.7% incidence rate of TEAEs. The investigators also noted that adverse events were consistent with those seen in the initial 6 months of treatment for patients originally randomized to lemborexant.

At study baseline for placebo subjects (n = 318), the median sSOL was 55.9, and the mean sSE and sWASO were 61.3 (SD, 17.8) and 132.5 (SD, 80.2), respectively.

The original full 12-month results of SUNRISE-2 were presented at World Sleep 2019, and showed that SOL was lowered by almost 20 minutes for patients treated with both 5-mg and 10-mg lemborexant, which maintained efficacy through months 6 and 12.²

Additional data from those who maintained treatment with lemborexant through the entire 12 months showed a change in sleep onset latency following 1 month of exposure of —17.2 minutes (SD, –19.8 to –14.6) for the 5-mg group from 57.3 (SD, 46.3) at baseline, persisting to –24.1 minutes and –25.8 minutes at 6 and 12 months, respectively. Likewise, The 10-mg group experienced a 1-month change of -18.6 minutes (SD, –21.3 to –16.0), maintained to –23.0 minutes and –26.3 minutes at 6 and 12 months, respectively, after a baseline of 60.2 (SD, 45.1).

Lemborexant was approved by the FDA for the treatment of insomnia in adults for both 5- and 10-mg doses in December 2019. The small molecule orexin receptor antagonist that binds to both orexin receptor 1 and 2 was approved based on data from both the phase 3 SUNRISE 1 and SUNRISE 2 studies.³ Months later, Eisai announced the availability of the newly FDA-approved treatment.⁴

REFERENCES

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

2. Yardley J, Kärppä M, Inoue Y, et al. Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: 12-monht results from SUNRISE- Presented at: World Sleep 2019; September 20-25; Vancouver, BC, Canada. Abstract 1663.

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 26, 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 26, 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