The small-molecule dual orexin receptor antagonist was approved based on data from 2 pivotal phase 3 studies which showed statistical superiority over placebo for sleep onset latency.
Lynn Kramer, MD
The FDA has approved Eisai’s lemborexant (Dayvigo) for the treatment of insomnia in adults. The drug, which will be available in 5 mg and 10 mg doses, is a small molecule orexin receptor antagonist that binds to both orexin receptor 1 and 2.1
The approval was based on data from 2 pivotal phase 3 studies, SUNRISE 1 and SUNRISE 2, that assessed lemborexant versus placebo for 1 and 6 months. The drug will be available early in 2020 following scheduling by the Drug Enforcement Administration.
"We believe the approval of Dayvigo is particularly exciting because it is the first FDA-approved medication to report safety data over a 12-month period along with sleep onset and sleep maintenance efficacy data over a six-month period in a pivotal clinical study," said Lynn Kramer, MD, Chief Clinical Officer, Neurology Business Group, Eisai, in a statement.1 "We look forward to making this new therapeutic option available to the millions of patients who suffer with insomnia.”
SUNRISE 1 was a 1-month, placebo- and active-controlled, double-blind study that included the first phase 3 head-to-head comparison versus zolpidem tartrate extended release, an active comparator, that evaluated the safety and efficacy of lemborexant in 1006 participants 55 years of age and older with insomnia. Lemborexant 5 mg and 10 mg demonstrated a statistically significant superiority over placebo on the primary end point, which was mean change in log-transformed latency to persistant sleep (LPS) from baseline to end of treatment. Treatment with the study drug also demonstrated statistically significant improvements in sleep efficiency and wake after sleep onset compared with placebo.
In SUNRISE 2, patients age 18 or older with insomnia were randomly assigned to lemborexant 5 mg, 10 mg, or placebo. Compared to placebo, the study drug was found to be statistically significantly superior on the primary end point, which was mean change from baseline to end of treatment at 6 months for log-transformed, patient-reported sleep onset latency. The study drug was also statistically superior to placebo on the secondary end points, including change from baseline to end of treatment on patient-reported sleep efficiency and wake after sleep onset. After 6 months of treatment, patients in the placebo group were re-randomized to either 5 mg or 10 mg lemborexant, while patients in the original treatment group maintained their therapy.
Twelve-month results2 from SUNRISE 2 showed that sleep onset latency was lowered by almost 20 minutes for patients treated with both 5 mg and 10 mg of lemborexant, with maintained efficacy through months 6 and 12. In addition, subjective sleep efficiency at baseline was 65.3% (SD, 19.1) and 64.7% (SD, 17.9) for the 5 mg and 10 mg dose groups, respectively, with increases of 6.4% (95% CI, 5.1 to 7.6) and 7.3% (95% CI, 6.1 to 8.6) in both groups at 1 month. At 6 and 12 months, the 5- and 10-mg dose groups had respective increases of 11.1% and 12.6%, and 11.1% and 13.7%.
Subjective wake after sleep onset decreased 17.3 minutes (95% CI, -22.5 to -12.0) in the 5-mg group and 18.7 minutes (95% CI, -24.1 to 13.3) in the 10-mg group after 1 month, followed by decreases of 36.1 and 31.5 minutes, respectively, at 6 months. After 1 year, the 5-mg and 10-mg groups had subjective wake after sleep onset decreases of 42.9 and 43.8 minutes, respectively.
Notably, rebound insomnia effects were not reported after discontinuation of lemborexant.
In addition to effects on sleep onset latency, additional investigations found that treatment with lemborexant had no statistically significant or clinically relevant effects on next-morning driving performance.3
“We hope that [lemobrexant] will provide a useful option, a potential option, for clinicians to consider when their patients have difficulty falling asleep or staying asleep, because it’s important not only to treat the symptoms, but also to make sure that they can wake well and that’s what these special studies were intended to help us understand,” Margaret Moline, PhD, International Project Team Lead of lemborexant at Eisai, told NeurologyLive in an interview at AAN 2019.
The most common adverse events reported in SUNRISE 1 and SUNRISE 2 was somnolence (10 mg, 10%; 5 mg, 7%; placebo, 1.0%). The most common adverse events leading to discontinuation of lemborexant were somnolence (10 mg, 1.0%; 5 mg, 0.7%; placebo, 0.4%) and nightmares (10 mg, 0.3%; 5 mg, 0.3%; and placebo, 0%).
1. 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. eisai.mediaroom.com/2019-12-23-U-S-FDA-Approves-Eisais-DAYVIGO-TM-lemborexant-for-the-Treatment-of-Insomnia-in-Adult-Patients. Accessed December 23, 2019.
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. Vermeern A, Jongen S, Murphy P, et al. On-the-road driving performance the morning after bedtime administration of lemborexant in healthy adult and elderly volunteers. SLEEP. 2018;1—9. doi: 10.1093/sleep/zsy260.