Eisai announced the U.S. FDA has approved Dayvigo (lemborexant) for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults. In the United States, Dayvigo will be commercially available in 5 mg and 10 mg tablets following scheduling by the U.S. Drug Enforcement Administration (DEA), which is expected to occur within 90 days.
The FDA approval was based on the results of a clinical development program that included two pivotal Phase III studies (SUNRISE 2 and SUNRISE 1), which evaluated Dayvigo versus comparators for up to one month and Dayvigo versus placebo for six-months, respectively.
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. Patients were randomized to placebo (n=325), Dayvigo 5 mg (n=323), or Dayvigo 10 mg (n=323) once nightly. 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 falling asleep. Pre-specified secondary efficacy endpoints were change from baseline to end of treatment at six months for patient reported sleep efficiency (sSE; defined as the proportion of time spent asleep during time in bed) and subjective sleep onset and sleep maintenance (sWASO; defined as the minutes of wake from the onset of persistent sleep until lights on). The primary and pre-specified 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 sSE and sWASO.
SUNRISE 1 was a short-term (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 criteria for insomnia disorder. Patients were randomized to placebo (n=208), Dayvigo 5 mg (n=266) or 10 mg (n=269) or active comparator (n=263) once nightly. 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 pre-specified secondary efficacy endpoints in SUNRISE 1 were the mean change from baseline to end of treatment (day 29/30) in sleep efficiency (SE) 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.
Across SUNRISE 2 and SUNRISE 1, DAYVIGO was not associated with rebound insomnia following treatment discontinuation, and there was no evidence of withdrawal effects following Dayvigo discontinuation at either dose. In addition, the development program included multiple safety studies evaluating effects on postural stability, cognition, driving performance and respiratory safety.
Eisai has submitted new drug applications seeking approval of this agent for use in the treatment of insomnia in Japan (March 2019) and Canada (August 2019).
Lemborexant binds to orexin receptors, OX1R and OX2R and acts as a competitive antagonist (IC50 values of 6.1 nM and2.6 nM, respectively). When activated, the role of OX1R is to suppress REM sleep, and the role of OX2R is to suppress both non-REM sleep and REM sleep. Lemborexant enables sleep by preventing activation of OX1R and OX2R.
Insomnia is characterized by difficulty falling asleep, staying asleep, or both, despite an adequate opportunity to sleep, that can lead to daytime consequences such as fatigue, difficulty concentrating and irritability. Insomnia is one of the most common sleep-wake disorders with high prevalence. Approximately 30% of adults worldwide have symptoms of insomnia, and many of them remain months to years. As a result, insomnia causes various social losses such as long absences and reduced productivity.