Eisai's Dual Orexin Receptor Antagonist DAYVIGO® (Lemborexant) Demonstrates Significant Improvement in Sleep Quality in Phase 3 Clinical Trial

December 28, 2019 News /BioonBIOON/ -- Japanese pharmaceutical company Eisai recently announced that the results of SUNRISE-1 (Study 304), a pivotal Phase III head-to-head study evaluating Dayvigo (lemborexant) for the treatment of insomnia, have been published online in JAMA Network Open. In this study, Dayvigo significantly improved sleep onset and sleep maintenance compared with placebo.Rosenberg R, et al. Comparison of lemborexant with placebo and zolpidem extended release in older adults with insomnia disorder: A phase 3 randomized clinical trial. JAMA Netw Open. 2019）。

This study was a global, randomized, double-blind, placebo-controlled and active-comparator-controlled, parallel-group study that enrolled a total of 1,006 adult patients aged ≥55 years with insomnia. In the study, patients were randomly assigned to receive Dayvigo 5 mg, Dayvigo 10 mg, placebo, or the active comparator zolpidem tartrate extended-release tablets, administered once daily at bedtime for one month. The primary endpoint was the change from baseline in latency to persistent sleep in the Dayvigo treatment groups compared with the placebo group. Key secondary endpoints included: (1) changes from baseline in sleep efficiency and wake after sleep onset for Dayvigo versus placebo; and (2) differences between Dayvigo and zolpidem tartrate in wake after sleep onset during the second half of the night.

The results showed that the study met both the primary and secondary endpoints. The objective outcomes for sleep onset and sleep maintenance assessed by polysomnography (PSG) and self-reported sleep diary (Fig. 2), as well as the subjective outcomes (Fig. 3), are presented below. Regarding safety, the treatment-emergent adverse events (TEAEs) reported in all treatment groups with an incidence ≥2% were headache (6.2% in the placebo group, 5.3% in the active control group, 6.4% in the Dayvigo 5 mg group, and 4.9% in the Dayvigo 10 mg group) and somnolence (1.9% in the placebo group, 1.5% in the active control group, 4.1% in the Dayvigo 5 mg group, and 7.1% in the Dayvigo 10 mg group).

Dayvigo (lemborexant) is an orexin receptor antagonist discovered and developed in-house by Eisai, which was recently approved by the U.S.FDAApproved for the treatment of insomnia in adults, a sleep-wake disorder characterized by difficulties with sleep onset and/or sleep maintenance. In accordance with the scheduling by the U.S. Drug Enforcement Administration (DEA), Dayvigo is expected to be launched within the next three months as 5 mg and 10 mg tablets.

It is estimated that insomnia affects one-third of adults. However, due to significant safety concerns associated with sleep medications, new therapies face a challenging path to gaining acceptance among physicians and patients. Earlier this year,FDABlack box warnings were issued for a class of insomnia medications, including Lunesta, Sonata, and Ambien, due to reports of injuries and fatalities resulting from hazardous activities such as sleepwalking and sleep-driving among patients taking these drugs.

Dayvigo inhibits orexin signaling by competitively binding to orexin receptors (OX1R and OX2R). Orexin is a naturally occurring chemical produced in the hypothalamus that regulates sleep and wakefulness. Dayvigo addresses both sleep onset and sleep maintenance issues, and its mechanism of action does not impair morning postural stability or cognitive function.

The orexin neuropeptide signaling system plays a role in wakefulness. Blocking the binding of the wakefulness-promoting neuropeptides orexin A and orexin B to the orexin receptors OX1R and OX2R is believed to inhibit arousal drive signals.

Lemborexant binds to the orexin receptors OX1R and OX2R. As a competitive antagonist, it exhibits stronger inhibitory activity against OX2R. Orexin signaling is associated with other physiological functions, such as memory, mood, motivation, and attention.

Therefore, in addition to irregular sleep-wake rhythm disorder (ISWRD), Eisai is also testing lemborexant for its application in Alzheimer’s disease (AD). Previously, the drug was co-developed by Eisai and Purdue Pharma; however, earlier this year, Eisai repurchased all rights to the drug. (Bioon.com)

Original Source:Pivotal Phase 3 Study of DAYVIGO? (lemborexant) for the Treatment of Insomnia Disorder Published in JAMA Network Open