Lemborexant Met Primary, Secondary Endpoints in Phase 3 Insomnia Study

Lynn Kramer, MD, Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai

Lynn Kramer, MD

Eisai and Purdue Pharma have announced positive results from SUNRISE 2, an ongoing phase 3 long-term efficacy and safety trial studying lemborexant for treatment of insomnia.

Researchers reported that at the end of the 6-month placebo-controlled treatment period, pre-specified primary and main secondary efficacy outcomes assessed by participant self-reports were met; the study is continuing up to 1 year.

At the end of 6 months, treatment with lemborexant 5 mg and 10 mg resulted in a statistically significant improvement in subjective sleep onset latency versus placebo, the primary endpoint. Additionally, both the lemborexant 5 mg and 10 mg doses provided a statistically significant improvement in sleep maintenance variables of subjective sleep efficiency and subjective wake after sleep onset versus placebo, the key secondary endpoints. Daily functioning measured by the Insomnia Severity Index was also improved by both doses compared to placebo. All endpoints were assessed by participant sleep diaries.

"Our aspiration for lemborexant is to bring to the millions of patients suffering from insomnia and other sleep-wake disorders an agent for sleep-wake regulation that improves their ability to fall asleep and stay asleep, and maintains efficacy over time," Lynn Kramer, MD, Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai, said in a statement. "In SUNRISE 2, lemborexant improved both time to sleep onset as well as sleep maintenance over a six-month period. With these results, we now look forward to proceeding with regulatory submissions for lemborexant to bring to patients a long-term treatment option for treating the sleep-wake disorder, insomnia."

SUNRISE 2, a 12-month randomized, controlled, double-blind study, enrolled 971 participants 18—88 years of age with insomnia disorder. The study period included a screening and 2-week placebo run-in period, a 52-week treatment period and a 2-week follow-up period.

For the first 6 months of study, participants were given lemborexant 5 mg or 10 mg, or placebo, orally in tablet form each night immediately prior to bed. All participants received lemborexant for at least 6 months of the study period.

The most common adverse effects greater than 5% in either the treatment arm and greater than placebo reported were somnolence, headache and influenza. Overall discontinuation rates due to adverse effects were comparable between placebo and the lemborexant 5 mg dose, and higher for the lemborexant 10 mg dose.

SUNRISE 2 is the second phase 3 trial of the dual orexin receptor antagonist to report positive data. SUNRISE 1, the first pivotal phase 3 study that achieved its primary and key secondary outcomes versus placebo, was a recently completed placebo-controlled, double-blind active comparator trial that studied the safety and efficacy of lemborexant versus placebo and versus zolpidem tartrate extended-release (zolpidem ER), an active comparator, in about 1000 participants 55 years of age and older with insomnia. SUNRISE 1 measured the change from baseline in both sleep onset and sleep maintenance variables, including the time spent awake in the second half of the night.

“As a clinician and researcher treating patients with insomnia and other sleep-wake disorders for 30 years, for me, successful treatment means that patients fall asleep fast, sleep well, and wake well, without functional impairment, or loss of effect over time,” said Russell Rosenberg, PhD, DABSM, a Principal Investigator in the lemborexant studies and former Chairman of the Board of the National Sleep Foundation in a statement. “The results of SUNRISE 2 are particularly encouraging for the many patients who suffer from chronic insomnia.”

The full data from the 12-month SUNRISE 2 trial will be presented at upcoming medical meetings in 2019. The companies hope to submit a new drug application for lemborexant in treatment of insomnia to the FDA in Eisai’s FY18.

Lemborexant is also under investigation in a phase 2 trial for treatment of irregular sleep-wake rhythm disorder and mild to moderate Alzheimer disease dementia.

Eisai and Purdue Pharma Announce Positive Topline Results of SUNRISE 2, the Second Phase 3 Pivotal Study of Lemborexant [news release]. Toyko and Stamford, CT: Eisai Co., Ltd; Oct. 17, 2018. https://www.prnewswire.com/news-releases/eisai-and-purdue-pharma-announce-positive-topline-results-of-sunrise-2-the-second-phase-3-pivotal-study-of-lemborexant-300732720.html. Accessed Oct. 18, 2018.