Dr Marge MolineMargaret Moline, PhD
At the Sleep Research Society's Advances in Sleep and Circadian Science conference, Eisai and Purdue Pharma presented 6-month results from SUNRISE 2, a phase 3 clinical trial that evaluated the safety and efficacy of lemborexant for the treatment of insomnia, reporting significant improvements in patient-reported measures of sleep onset and sleep maintenance.

At the end of the 6-month, placebo-controlled treatment period, subjects treated with either 5 mg or 10 mg lemborexant were found to have statistically significant improvements compared to placebo in patient-reported sleep onset latency, and subjective sleep efficiency and subjective wake after sleep onset.

“It's important to be able to have data on both sleep onset and sleep maintenance because patients can complain about difficulty falling asleep or staying asleep or both.  This describes the participants in our study— potential subjects could come in with a sleep onset complaint or a sleep maintenance complaint or both,” Margaret Moline, PhD, International Project Team Lead for the lemborexant clinical development program, told NeurologyLive in an interview. “I think one of the important parts of our program was that the treatment was studied for 6 months in a placebo-controlled condition, and since many patients may be taking medication over the long term, it's important to have data that suggest that the drug will be effective and well-tolerated across long periods.”

SUNRISE 2, a 12-month randomized, controlled, double-blind, parallel-group study, assessed the long-term efficacy and safety of lemborexant in the outpatient setting of 949 adult patients with insomnia disorder—about 28% of study participants were 65 years of age and older. The trial included a pre-randomization phase of up to 35 days—which consisted of a 2-week placebo run-in period—a randomization phase of a 6-month placebo-controlled period, a 6-month period of active-only treatment, and a 2-week period without treatment prior to the end-of-study visit. Data were collected every day from participants through a sleep diary.

During the placebo-controlled treatment phase, participants were evenly randomized to lemborexant 5 mg, 10 mg, or placebo. In the active-only treatment period, those who received placebo during the first period were re-randomized to lemborexant 5 mg or 10 mg and continued in the study until the 12-month period. Participants who received 5 mg and 10 mg lemborexant in the first period continued on the treatment to which they were originally randomized until the end of the 12-months.

The primary endpoint was to determine the efficacy of lemborexant 5 mg and 10 mg compared to placebo on patient-reported sleep onset latency at the end of 6 months, while secondary endpoints included the mean change in subjective sleep efficiency and subjective wake after sleep onset for lemborexant 5 mg and 10 mg compared to placebo at the end of 6 months; the endpoints were assessed by patient self-reports via electronic sleep diaries.

“This was the second pivotal study that reported data; we already had a successful phase 2 proof-of-concept study that helped us select the doses to move forward to phase 3,” Moline concluded. “We previously reported our results from SUNRISE 1 and showed that the objective measures of sleep onset and sleep maintenance were statistically significant compared to placebo. Included in that study were the sleep diary endpoints, the same that we used in this study. Because of the good efficacy that we've seen in the other study, we were expecting to see good efficacy in this study.”

After the 6-month treatment period, researchers concluded that treatment with either 5 mg or 10 mg lemborexant resulted in statistically significant improvements compared to placebo in the study’s primary efficacy endpoint and secondary endpoints. Investigators reported that median reductions in sleep onset latency with lemborexant 5 mg (-21.81 minutes) and 10 mg (-28.21 minutes) were larger and statistically significant compared to placebo (-11.43 minutes) (P <.0001 for all treatment groups). Improvements measured by Least Squares Mean in subjective sleep efficiency with lemborexant 5 mg (14.19%, P = .0001) and 10 mg (14.31%, P <.0001) were also statistically significant compared to placebo (9.64%). Reductions in subjective wake after sleep onset, measured by Least Squares Mean) with lemborexant 5 mg (-46.75 minutes, P = .0005) and 10 mg (-41.95 minutes, P = .0105) were also statistically significant compared with placebo (-29.29 minutes).1

The most commonly reported adverse effects were mild to moderate; the most commonly reported adverse effects greater than 5% in either treatment arm greater than placebo were somnolence, headache, and influenza. Serious adverse effects were reported in 2.2% of the lemborexant 5 mg arm, 2.9% of the lemborexant 10 mg arm, and 1.6% in placebo, and only 1 was considered treatment-related. Discontinuation rates because of adverse effects were comparable between placebo (3.8%) and lemborexant 5 mg (4.1%), and higher for lemborexant 10 mg (8.3%).

Since the data right now are focused on the first 6 months of SUNRISE 2, more data will be released on the second half of the study.

In December, Eisai and Purdue submitted a new drug application (NDA) to the FDA for lemborexant, seeking approval for treatment of insomnia. The NDA was backed by SUNRISE 1 and SUNRISE 2, the 2 pivotal phase 3 safety and efficacy studies of lemborexant, as well as important safety studies like assessment of postural stability after middle-of-the-night awakening, and a next-morning driving study.
1. Eisai and Purdue Pharma Present Efficacy and Safety Data from Second Pivotal Phase 3 Study at the Sleep Research Society's Conference: Advances in Sleep and Circadian Science [news release]. Tokyo and Stamford, Conn.: Eisai Co. and Purdue Pharma; Feb. 4, 2019. http://eisai.mediaroom.com/2019-02-04-Eisai-and-Purdue-Pharma-Present-Efficacy-and-Safety-Data-from-Second-Pivotal-Phase-3-Study-at-the-Sleep-Research-Societys-Conference-Advances-in-Sleep-and-Circadian-Science. Accessed Feb. 4, 2019.