Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that a marketing authorization application has been submitted in Japan for lemborexant, an investigational agent for sleep-wake regulation, seeking approval for use in the treatment of insomnia disorder.
This application was based on the results of two pivotal Phase III clinical studies in patients with insomnia, SUNRISE 1 (Study 304) and SUNRISE 2 (Study 303), enrolling approximately 2,000 patients combined, as well as important safety studies, including assessment of postural stability after middle-of-the-night awakening, and a next-morning driving study (Study 106, Study 108).
SUNRISE 1 was a placebo-controlled 1-month Phase III clinical study evaluating the efficacy and safety of lemborexant versus zolpidem tartrate extended release (“zolpidem ER”) in 1,006 male or female adult patients 55 years and older (45% of patients were 65 years and older) with insomnia disorder, which was characterized by difficulty staying asleep. The study objectively assessed sleep latency (time taken between going to bed and falling asleep, primary objective), sleep efficiency and wake after sleep onset (effect on maintaining sleep, secondary objectives) using polysomnography. The results of the study showed that lemborexant 5 mg and 10 mg had statistically significant improvement compared to zolpidem ER 6.25 mg and placebo in sleep parameters evaluated in primary and key secondary objectives. In this study, lemborexant had rates of discontinuation due to adverse events (AEs) comparable to placebo, with the most common AEs in the lemborexant arms being headache and somnolence.
SUNRISE 2 was a placebo-controlled 12-month Phase III clinical study conducted globally including in Japan to evaluate the long-term efficacy and safety of lemborexant in 949 male or female adult participants 18 to 88 years of age with insomnia disorder, which was characterized by difficulty falling asleep and/or staying asleep. During the first six months, patients were administered either lemborexant (5 mg, 10 mg) or placebo. The study evaluated sleep onset latency (primary objective), subjective sleep efficiency, and subjective wake after sleep onset (secondary objectives) by using patient reported (subjective) sleep diaries. From an analysis of results at the end of the six-month, placebo-controlled treatment period, the primary efficacy endpoint and all secondary endpoints were achieved for both lemborexant arms, and statistically significant improvement in sleep onset and sleep maintenance was confirmed for both lemborexant arms compared to placebo during the six-month treatment period. Although the rate of discontinuation due to AEs for lemborexant 5 mg was comparable to placebo, the rate of discontinuation due to AEs for lemborexant 10 mg was higher than placebo. The most common AEs in the lemborexant arms were somnolence, headache and influenza.
Lemborexant acts on the orexin neurotransmitter system and is believed to regulate sleep and wake by dampening wakefulness without impeding the ability to awaken to external stimuli. Lemborexant is being developed for the treatment of multiple sleep-wake disorders, including insomnia disorder. In addition to this marketing authorization application submitted in Japan, a New Drug Application was submitted in the United States to the Food and Drug Administration on December 27, 2018.
Furthermore, a Phase II clinical study of lemborexant in patients with irregular sleep-wake rhythm disorder and mild to moderate Alzheimer’s dementia is ongoing.
It is estimated that approximately 1 in every 5 people (over 20 million people) in Japan suffers from a sleep disorder, and the number of patients being examined at medical institutions continues to increase. Eisai is striving to address new unmet medical needs and contribute to further increasing the benefits for patients and their families.