TOKYO :Eisai Co., Ltd. announced today that its U.S. subsidiary Eisai Inc. has launched its in-house discovered orexin receptor antagonist DAYVIGO (lemborexant) CIV for the treatment of adults with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance in the U.S. on June 1, 2020.

Discovered at Eisai’s Tsukuba Research Laboratories and developed in-house, DAYVIGO is a small-molecule compound. The mechanism of action in the treatment of insomnia is presumed to be through antagonism of orexin receptors1. The orexin neuropeptide signaling system plays a role in wakefulness(1). Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to orexin receptors OX1R and OX2R is thought to suppress wake drive. Lemborexant binds to orexin receptors OX1R and OX2R and acts as a competitive antagonist (IC50 values of 6.1 nM and 2.6 nM, respectively).

DAYVIGO was approved in the U.S. by the U.S. Food and Drug Administration (FDA) based on findings from the lemborexant clinical development program, which included two pivotal Phase 3 studies(2) (SUNRISE 1 and SUNRISE 2) in nearly 2,000 adult patients with insomnia.

SUNRISE 1 was a one month, randomized, double-blind, placebo- and active-controlled multi-center, parallel-group clinical trial in adult female subjects age 55 and older and male subjects 65 years and older who met DSM-5 (the Diagnostic and Statistical Manual of Mental Disorders – 5th edition) criteria for insomnia disorder. The primary efficacy endpoint was the mean change in latency to persistent sleep (LPS; defined as the number of minutes from lights off to the first 10 consecutive minutes of non-wakefulness) from baseline to end of treatment (day 29/30), as measured by overnight polysomnography (PSG) monitoring. The secondary efficacy endpoints in SUNRISE 1 were the mean change from baseline to end of treatment (day 29/30) in sleep efficiency (SEF) and wake after sleep onset (WASO) measured by PSG. In SUNRISE 1, DAYVIGO 5 mg and 10 mg demonstrated statistically significant superiority on the primary efficacy measure, LPS, compared to placebo. DAYVIGO 5 mg and 10 mg demonstrated statistically significant improvement in SE and WASO compared to placebo and active-controlled.

SUNRISE 2 was a long-term (six month), randomized, double-blind, placebo-controlled, multi-center, trial in adult patients age 18 or older who met DSM-5 criteria for insomnia disorder. The primary efficacy endpoint was the mean change from baseline to end of treatment at six months for patient-reported (subjective) sleep onset latency (sSOL), defined as the estimated minutes from the time that the subject attempted to sleep until sleep onset. Pre-specified secondary efficacy endpoints for sleep maintenance were change from baseline to end of treatment at six months for patient-reported sleep efficiency (sSEF; defined as the proportion of time spent asleep per time in bed) and wake after sleep onset (sWASO; defined as the minutes of wake from the onset of sleep until wake time). The pre-specified primary and secondary efficacy endpoints were measured using a Sleep Diary. In SUNRISE 2, DAYVIGO 5 mg and 10 mg demonstrated statistically significant superiority on the primary efficacy measure, sSOL, compared to placebo. DAYVIGO 5 mg and 10 mg also showed statistically significant superiority in sSEF and sWASO.(1)

Analyses in both studies suggested DAYVIGO was not associated with rebound insomnia, and there was no evidence of withdrawal effects following treatment discontinuation, suggesting it does not produce physical dependence in those taking it for up to one year. DAYVIGO is the first FDA-approved insomnia medication with safety data over a 12-month treatment period and with sleep onset and sleep maintenance efficacy data over a six-month treatment period in a pivotal clinical study.

The most common adverse reaction (reported in 5% or more of patients treated with DAYVIGO and at least twice the rate of placebo) in the SUNRISE1 and SUNRISE2 (SUNRISE2 was initiated 30 days after first dosing) studies was somnolence (DAYVIGO 10 mg, 10%; DAYVIGO 5 mg, 7%; placebo, 1%).

In a special safety study (Study 106)(3), DAYVIGO at 5 mg and 10 mg doses did not cause statistically significant impairment in next morning driving performance in healthy adult or elderly subjects (compared with placebo). Impairment was seen in some people taking the 10 mg dose. Patients using the 10 mg dose should be cautioned about the potential for next-morning driving impairment because there is individual variation in sensitivity to DAYVIGO. Additional special safety studies (Study 108)(4) evaluated middle-of-the-night safety, next morning postural stability and memory. The effects of Dayvigo on next day postural stability and memory were evaluated in two randomized, placebo and active-controlled trials in healthy subjects and insomnia patients age 55 and older. There were no meaningful differences between DAYVIGO and placebo on next-day postural stability or memory at either dose. Patients should be cautioned about the potential for middle-of-the-night postural instability as well as attention and memory impairment.

DAYVIGO (5 mg, 10 mg tablets) received approval from the U.S. FDA in December 2019, and was designated as a Schedule IV controlled substance by the U.S. Drug Enforcement Administration (DEA) in April 2020. According to this Schedule IV designation, individuals with a history of abuse or addiction to alcohol or other drugs may be at an increased risk for abuse and addiction to DAYVIGO and such patients should be followed carefully. Eisai received manufacturing and marketing approval for DAYVIGO as an insomnia treatment in Japan in January 2020, and was included in Japan’s National Health Insurance Drug Price List in April 2020. It is being prepared for launch in Japan. Eisai has also submitted a new drug application seeking approval of this agent for use in the treatment of insomnia in Canada in August 2019.

Insomnia is characterized by difficulty falling asleep, staying asleep, or both, despite an adequate opportunity to sleep(5)(6). Insomnia is one of the most common sleep-wake disorders with high prevalence. Approximately 30% of adults worldwide have symptoms of insomnia(7)(8) and many of them persist for months to years.

With the launch of DAYVIGO and through its continuing research and development efforts focusing on orexin biology, Eisai aspires to improve the lives of patients suffering from sleep disorders.