New medicine for insomnia! Phase III of ldayvigo (lemborexant), a dual effect orexin receptor antagonist of Weicai, significantly improved sleep quality!

December 28, 2019 / BIOON / -- Eisai, a Japanese pharmaceutical company, recently announced that the results of sunrise-1 (304 study), a key phase III head-on study for the treatment of insomnia by dayvigo (lemborexant), had been published online in the journal JAMA network open In this study, dayvigo significantly improved sleeping and sleep maintenance compared to 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 is a global, randomized, double-blind, placebo-controlled, positive drug-controlled, parallel group study, involving 1006 adults with insomnia aged ≥ 55 years In the study, patients were randomly assigned to receive dayvigo 5mg, dayvigo 10mg, placebo, positive control drug zolpidem tartrate sustained-release agent, before sleep, treatment for one month The primary end point of the study was the change from baseline in latency to duration of sleep in the dayvigo and placebo groups Key secondary endpoints included: (1) changes in sleep efficiency and post sleep wake relative to baseline in dayvigo compared to placebo; and (2) differences in post sleep wake in dayvigo compared to zolpidem tartrate The results showed that the primary and secondary endpoints were reached The objective results (Fig2) and subjective results (Fig3) of sleep and sleep maintenance assessed by PSG and self-reported sleep diary are as follows In terms of safety, headache (6.2% in placebo group, 5.3% in effective control group, 6.4% in dayvigo 5mg group, 4.9% in dayvigo 10mg group) and drowsiness (1.9% in placebo group, 1.5% in effective control group, 4.1% in dayvigo 5mg group, 7.1% in dayvigo 10mg group) were reported as adverse events (teaes) in all treatment groups with incidence ≥ 2% Dayvigo (lemborexant) is an orexin receptor antagonist discovered and developed by Weicai It was approved by the US FDA recently to treat adult insomnia, which is a sleep wake disorder characterized by difficulty in falling asleep and / or maintaining sleep According to the plan of the United States regulatory (special) Drug Administration (DEA), dayvigo will be available in 5mg and 10mg tablets in the next three months It is estimated that insomnia affects one third of adults But because safety is a big problem of sleep drugs, the new therapy faces a difficult process in obtaining the approval of doctors and patients Earlier this year, the FDA issued a black box warning on a number of insomnia drugs, including lunesta, Sonata and Ambien, due to reports that dangerous activities such as sleepwalking and sleep driving among patients taking the drugs resulted in casualties Dayvigo suppresses orexin signals by competitively binding orexin receptors (ox1r and ox2r) Orexin is a chemical produced naturally in the hypothalamus, which is involved in sleep and arousal Dayvigo is a product that can solve both sleeping problems and sleep maintenance problems Its mechanism of action will not damage the stability of posture and cognitive ability in the morning The molecular structure of lemborexant (image source: Wikipedia) the orexin neuropeptide signal system plays a role in arousal Blocking arousal promotes the binding of orexin A and orexin B to orexin receptor ox1r and ox2r, which is believed to inhibit the arousal driving signal Lamborexant can bind orexin receptors ox1r and ox2r As a competitive antagonist, it has a stronger inhibitory effect on ox2r Orexin signals are associated with other physiological functions, such as memory, mood, motivation, and attention Therefore, in addition to the awakening rhythm disorder (iswrd), Weicai is also testing the application of lemborexant in Alzheimer's disease (AD) Previously, the drug was jointly developed by Weicai and Purdue, but earlier this year, Weicai repurchased all rights to the drug Original source: pivotal phase 3 study of dayvigo? (lamborexant) for the treatment of insomnia disorder published in JAMA network open