This leaves sufferers with daytime consequences including fatigue, irritability and difficulty concentrating.
Poor sleep is also associated with a variety of health consequences, such as an increased risk of hypertension, diabetes, obesity, depression, heart attack, stroke and dementia, quite apart from the negative impact on mood and behaviour. As we age, it becomes more prevalent.
A new potential treatment, lemborexant, is being developed by Eisai and Imbrium Therapeutics.1 It inhibits orexin signalling by binding to both orexin receptor subtypes.
Orexin signalling is thought to promote periods of wakefulness in people with normal sleep–wake rhythms; in abnormal circumstances, inhibiting inappropriate orexin signalling may facilitate the initiation and maintenance of sleep.
In a multicentre, randomised, double-blind, placebo-controlled, adaptive, parallel group clinical trial, 291 adult and elderly subjects with insomnia were enrolled.2
Subjects were given 1, 2.4, 4, 10, 15 or 25 mg of lemborexant, or a placebo, for 15 nights. The study was stopped for early success after the fifth interim analysis when the 15 mg dose met the efficacy and safety criteria; three other doses also met the criteria.
Compared with the placebo, subjects had significant improvements in sleep efficacy, latency to persistent sleep and subjective sleep onset latency. Adverse events were mostly mild or moderate, including dose-related somnolence.
Two Phase III studies have also been reported. In one, 1006 patients aged 55 and older with insomnia were given 5 or 10 mg of lemborexant or 6.5 mg of the active comparator, extended release zolpidem.3
After a prerandomisation phase of up to 35 days, including a two-week placebo run-in period, there was a 30-day treatment period and a treatment-free period of at least two weeks at the end. Polysomnography showed that lemborexant was superior to the placebo at both doses as measured by latency to persistent sleep after the month’s treatment.
Top-line results from the second trial, in 949 adult patients, have been announced via press release.
Subjects were given 5 or 10 mg of lemborexant or a placebo for six months after a similar run-in period, followed by a six-month period of active-only treatment in which the placebo group was rerandomised to one of the active groups. Efficacy objectives, including sleep onset latency, sleep efficiency and wake after sleep objects were all met for the drug.
References
- C.T Beuckmann, et al., J. Pharmacol. Exp. Therap. 362, 287 (2017).
- P. Murphy, et al., J. Clin. Sleep. Med. 13, 1289 (2017).
- Presentation at the 43rd Annual Meeting of the Japan Society of Sleep Research (Sapporo, Japan, 11–13 June 2018), Abst. S11-4.