Fazamorexant (YZJ-1139): A Comprehensive Pharmacological and Clinical Profile of a Novel Dual Orexin Receptor Antagonist

Executive Summary

Fazamorexant (developmental code: YZJ-1139) is a novel, orally administered small molecule drug emerging as a significant contender in the therapeutic landscape for insomnia. Classified as a dual orexin receptor antagonist (DORA), it represents the latest evolution in sleep medicine, which has shifted from inducing broad central nervous system sedation to targeting the specific neurobiological pathways that regulate wakefulness. Developed through a collaboration between Chinese pharmaceutical leaders Jiangsu Yangtze River Pharmaceutical Group and Shanghai Haiyan Pharmaceutical Technology Co., Ltd., Fazamorexant is in the late stages of clinical development, with its primary indication being the treatment of sleep initiation and maintenance disorders.[1]

The most defining and strategically significant attribute of Fazamorexant is its distinct pharmacokinetic profile, characterized by rapid absorption and an exceptionally short elimination half-life of approximately 1.9 to 3.7 hours.[1] This "fast-on, fast-off" characteristic theoretically positions it to offer a best-in-class profile for minimizing the next-day residual sedation, cognitive impairment, and "hangover" effects that have long been the principal limitation of hypnotic agents, including some first-generation DORAs. By providing therapeutic effect throughout a standard sleep period and then clearing rapidly from the system, Fazamorexant aims to restore normal sleep patterns without compromising daytime function.