New Insomnia Drug Appears Safe, Effective in Older Patients

Clinicians may soon have a new option for treating insomnia in older patients, new research suggests.

Subanalyses from the phase 3 SUNRISE-1 trial showed that lemborexant (Eisai Inc), an investigational dual orexin receptor antagonist being developed for the treatment of insomnia and irregular sleep-wake rhythm disorder, was both safe and effective in an older population — and was not different from placebo on postural stability.

The results suggest that this new agent may be a suitable treatment for patients aged 65 years and older with insomnia disorder, the investigators note.

“We showed that the drug was effective on the objective endpoints of the study, which included efficacy in helping patients with sleep onset and with sleep maintenance, and the drug was well tolerated,” study author Margaret Moline, PhD, executive director of clinical development of Eisai’s Neurological Business Group, told Medscape Medical News.

The findings were presented here at the American Association for Geriatric Psychiatry (AAGP) 2019 Annual Meeting.

Facilitates Sleep

Lemborexant inhibits orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptor 1 and 2). In individuals with normal daily sleep-wake rhythms, orexin signaling is believed to promote periods of wakefulness; but in those with sleep-wake disorders, orexin signaling may not be functioning normally.

“Blocking the orexin signaling at bedtime is thought to dampen wakefulness so sleep can happen at the appropriate time,” said Moline.

Two pivotal phase 3 studies (SUNRISE-1 and SUNRISE-2) investigated lemborexant in patients with a history of subjective wake after sleep onset (WASO) of 60 or more minutes at least three times a week in the previous 4 weeks.

SUNSHINE-1 was a 1-month, multicenter randomized double-blind, placebo-controlled study. It incorporated both objective outcomes using polysomnography sleep studies and subjective outcomes using sleep diaries. It included over 1000 participants with insomnia disorder, defined as an Insomnia Severity Index score of 13 or more.

SUNRISE-2 was a 12-month study that subjectively assessed the ability to fall asleep and stay asleep based on patient self-reports — again using sleep diaries.

Both studies compared lemborexant with a placebo. SUNSHINE-1 also had an active comparator arm (6.25 mg of zolpidem tartrate extended release [ER]). Zolpidem targets a different neurotransmitter system than lemborexant and is a type-A GABA receptor agonist.

“These two drugs are from totally different classes of drugs,” said Moline. …

https://www.medscape.com/viewarticle/910030