失眠治疗新药物双重食欲素受体拮抗剂:达利雷生

Introduction: Swiss Actelion Biopharmaceutical Company, which was acquired by Johnson & Johnson Pharmaceuticals (J.&J.) Co., Ltd. in the late 1990s, began research and development. In December 2019, Idorsia Biopharmaceutical Company signed an exclusive agreement with Japan's Mochida Pharmaceutical Company to jointly develop, market and supply DaliRasen for the treatment of sleep disorders. DaliRazen is a dual orexin receptor (orexin receptor) antagonist, which inhibits the overactive insomnia state by blocking the combination of orexin receptors and the wake-promoting neuropeptide orexin.

The effects of daliramin

As a drug, daliramin has a unique and precise mechanism of action. It blocks the binding of arousal-promoting neuropeptides OXA and OXB to OX1R and OX2R receptors, effectively inhibiting arousal drive and helping people obtain deeper sleep. More importantly, DaliRasen can selectively target orexin nerves and inhibit the downstream neural pathways that promote wakefulness. This selectivity allows Dalirasin to exert its medicinal effect while minimizing the impact on other neural pathways.

Therapeutic effect

The phase III clinical trial study has obtained preliminary results. The study included two pivotal trials, including 1,874 adult patients with insomnia, who were randomly assigned to receive different doses of dalirasam or placebo, administered once a day. The primary efficacy endpoints were changes in latency to persistent sleep (LPS) and awakening after sleep onset (WASO) from baseline to 1 and 3 months. LPS is an indicator of falling asleep, and WASO is an indicator of sleep maintenance. The secondary endpoint was patient subjective total sleep time (sTST). The results showed that compared with the placebo group, the dose of 50 mg of dalirasin could significantly improve the patient's objective indicators of falling asleep and maintaining sleep, as well as the total sleep time reported by the patient; and reduce the next day's sleepiness.

Safety

During the double-blind treatment period of the global confirmatory Phase III clinical studies 301 and 302, the most commonly reported adverse event (AE, reported by at least 2% of subjects and >1% difference from placebo) was headache. Other AEs were fatigue, dizziness, nausea, and somnolence, which did not occur at a frequency >4% in any treatment group. Most AEs ranged in severity from mild to severe. For any drug, safety is always the primary consideration, therefore, continuous monitoring and evaluation of AEs is key to ensuring safe use of the drug.