Year-long data presented at World Sleep 2019 suggest that Eisai’s lemborexant is safe and effective in treating adults with insomnia, supporting its recently submitted NDA. It is set to be reviewed by the FDA by late December.
Margaret Moline, PhD
New 12-month results from the SUNRISE-2 study of lemborexant suggest that the investigational agent being studied for the treatment of insomnia is well tolerated and effective over the course of 1 year of exposure to 2 doses.1
Sleep onset latency was lowered by almost 20 minutes for patients treated with both 5 mg and 10 mg lemborexant, with maintained efficacy through months 6 and 12. Additionally, the Eisai agent, which is also under investigation in a phase 2 trial for the treatment of irregular sleep-wake rhythm disorder and mild to moderate Alzheimer disease dementia, was found to be safe.
Study author Margaret Moline, PhD, international project team lead, Eisai, and colleagues concluded that “these results support lemborexant as a potential treatment option for insomnia disorder with long-term effectiveness and safety.” The data were presented at World Sleep 2019, September 20 to 25, in Vancouver, British Columbia, Canada.
"The analysis of long-term data from SUNRISE 2 examines the effectiveness and safety/tolerability of lemborexant, as well as its impact on patient-reported sleep quality and next-morning alertness measures across 12 months of treatment, and further reinforces our confidence in its role as a potential treatment option for insomnia," said Lynn Kramer, MD, Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai, in a statement.2
The phase 3 SUNRISE-2 study randomized patients to either placebo or lemborexant in a dose of 5 mg or 10 mg, following a 2-week placebo run-in period. After 6 months, patients in the placebo group were re-randomized to either 5 mg or 10 mg, while patients in the original treatment group maintained their therapy. This brought the cohorts to 444 patients in the lemborexant 5-mg group and 437 patients in the lemborexant 10-mg group.
The change in sleep onset latency following 1 month of exposure was -17.2 minutes (standard deviation [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).
Subjective sleep efficiency at baseline was 65.3% (SD, 19.1) and 64.7% (SD, 17.9) for the lower and higher 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 months. At 6 and 12 months, the low- and high-dose groups had respective increases of 11.1% and 12.6%, 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.
"Insomnia is often a chronic condition for which patients may require treatment over an extended period of time, underscoring the need for safe and effective treatments,” Kramer said. “These results are important because lemborexant is the first investigational compound to report both sleep onset and sleep maintenance data over a 12-month period in a pivotal clinical study."
The incidence of treatment-emergent adverse events (AEs) was similar between the Eisai agent at both a dose of 5 mg and 10 mg, occurring at rates of 66.9% and 66.1%, respectively. The most common AEs were somnolence, nasopharyngitis, headache, and influenza, all occurring at a rate >5%. Discontinuations occurred but at low rates—5.1% in the 5-mg group and 9.4% in the 10-mg group. As for serious AEs, about 4% of patients reported experiencing one, with no deaths.
In March, the FDA accepted for review a new drug application (NDA) for lemborexant, with its Prescription Drug User Fee Act (PDUFA) date set for December 27, 2019. The submission is backed by data from a clinical development program that included SUNRISE-2, in addition to SUNRISE-1 and important safety studies like the assessment of postural stability after middle-of-the-night awakening and a next-morning driving study.
1. 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-2. Presented at: World Sleep 2019; September 20-25; Vancouver, BC, Canada. Abstract 1663.
2. Three New Analyses of Data Expand Understanding of the Potential Role for Investigational Agent Lemborexant in Insomnia and Irregular Sleep-Wake Rhythm Disorder [press release]. Woodcliff Lake, NJ: Eisai; Published September 27, 2019. prnewswire.com/news-releases/three-new-analyses-of-data-expand-understanding-of-the-potential-role-for-investigational-agent-lemborexant-in-insomnia-and-irregular-sleep-wake-rhythm-disorder-300927007.html. Accessed September 30, 2019.