The investigational dual-orexin antagonist from Eisai was significantly better at reducing Insomnia Severity Index-measured symptom severity in more than 1000 adults with insomnia in 2 phase 3 studies.
Thomas Roth, PhD
The impact of the severity of insomnia symptoms has been shown to be decreased by treatment with lemborexant, an investigational dual antagonist of the orexin OX₁ and OX₂ receptors, in a recently conducted assessment from a pair of phase 3 studies.1
The results of the SUNRISE-1 (NCT02783729) and SUNRISE-2 (NCT02952820) studies were used to conduct this symptom severity analysis. Ultimately, data revealed that roughly one-third of the patients randomized to either lemborexant 5-mg or 10-mg doses experienced a decline in Insomnia Severity Index (ISI) which was below the threshold for clinically important insomnia. The data were presented at SLEEP 2019, June 8-12 in San Antonio, Texas.
Led by Thomas Roth, PhD, director, sleep disorders and research center, Henry Ford Hospital, the investigators undertook a 1-month blinded assessment in SUNRISE-1 and 12-month study in SUNRISE-2 of 1965 patients with insomnia over the age of 55 years with a baseline ISI score ≥13 post-placebo run-in (SUNRISE-1), aged ≥18 years with insomnia and a baseline total ISI score of ≥15 after placebo run-in (SUNRISE-2). In SUNRISE-1, 1006 of those patients in were randomized to the 2 doses of lemborexant, placebo, or an active control group who were given zolpidem extended release. In SUNRISE-2, there were 959 patients randomized to either of the doses of lemborexant or placebo.
Roth and colleagues noted that “in both studies, ISI was administered at baseline and Month 1,” and the analysis was conducted with the region, study, and age group as factors, and the Cochran-Mantel-Haenszel test stratified patients by study, region and age group for responder rate analyses.
At baseline, the mean baseline total score was 19.2 for placebo, 19.3 for the 5-mg dose, and 19.0 for the 10-mg dose. At Month 1, the mean total ISI score was decreased for all groups, though the decreases were significantly bigger for those administered lemborexant in doses of 5-mg and 10-mg compared to placebo (P <.0001).
The investigators observed a larger percentage of patients treated with lemborexant experience ≥7-point decreases in total ISI score than placebo. Respectively, the 5-mg group and 10-mg group saw this increase in 47.3% and 47.8% of patients compared to 33.6% of placebo patients. As well, the percentage of patients whose total ISI score was <10 at Month 1 (the insomnia threshold), was 20.3% for placebo compared to 33% and 33.4% for lemborexant 5-mg and lemborexant 10-mg, respectively, which were significantly different (P <.0001).
In March 2019, the FDA accepted a new drug application (NDA) for lemborexant in the treatment of insomnia. Eisai Co, the manufacturer of the agent, submitted the SUNRISE-1 and SUNRISE-2 trials as supporting data, in addition to a number of safety studies.2
Principal investigator in these studies, Russell Rosenberg, PhD, D.ABSM, founder and CEO, NeuroTrials Research, told NeurologyLive® in March that “from a fairness perspective, there’s no perfect sleep-promoting agent. We know what the ideal sleep agent is, but I think we’re getting closer with lemborexant.”
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1. Roth T, Rosenberg R, Murphy P, et al. Lemborexant treatment for insomnia in phase 3: impact on disease severity. Sleep. 2019;42(Suppl 1): A151. doi: 10.1093/sleep/zsz067.362. Presented at: SLEEP 2019. June 8-12, 2019; San Antonio, TX. Abstract 0371.
2. Eisai and Imbrium Therapeutics Announce U.S. FDA Filing Acceptance of New Drug Application for Lemborexant for the Treatment of Insomnia [news release]. Tokyo and Stamford, Conn.: Eisai Co., Ltd.; March 11, 2019. prnewswire.com/news-releases/eisai-and-imbrium-therapeutics-announce-us-fda-filing-acceptance-of-new-drug-application-for-lemborexant-for-the-treatment-of-insomnia-300809862.html?tc=eml_cleartime. Accessed June 10, 2019