Lemborexant Improves Sleep Outcomes Following Placebo Randomization Switch

August 27, 2020
Marco Meglio
Marco Meglio

Marco Meglio, Associate Editor for NeurologyLive, has been with the team since October 2019. Follow him on Twitter @marcomeglio1 or email him at mmeglio@neurologylive.com

Benefit from lemborexant was evident after 1 month of switching from placebo to the active treatment and was sustained through the entirety of the 12-month trial.

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

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