On December 17, 2023, the Chinese Phase III clinical study of Daridorexant Hydrochloride Tablets （Daridorexant）, dosed the first patient at the Hebei Medical University Third Hospital. Daridorexant is a novel sleep medication collaborated between Simcere Pharmaceutical Group Limited (Simcere; 2096.HK) and Idorsia Pharmaceutials Ltd. (Idorsia), for the treatment of adult patients with insomnia characterised by symptoms present for at least 3 months and considerable impact on daytime functioning.
This study is led by Professor Yuping Wang at Xuanwu Hospital of Capital Medical University and conducted in 33 centers across China. It is a local pivotal registry study of Daridorexant in China.
Insomnia disorder is defined as difficulty initiating or maintaining sleep, causing clinically significant distress or impairment in important areas of daytime functioning. This impact on sleep quantity or quality should be present for at least three nights per week, lasts for at least three months, and occurs despite an adequate opportunity to sleep. A recent meta-analysis of the prevalence of insomnia in the Chinese general population showed that the prevalence of insomnia in China is about 15%, with hundreds of millions of people suffering from insomnia. There is a strong demand from insomnia sufferers for innovative medicines that can improve the quantity and quality of sleep, and daytime function.
Daridorexant is a dual orexin receptor antagonist (“DORA”), acting on both orexin 1 and orexin 2 receptors and equipotent on both. The orexin neuropeptides (orexin A and orexin B) act on orexin receptors to promote wakefulness. Rather than inducing sleep through broad inhibition of brain activity, Daridorexant antagonizes only the activation of orexin receptors and consequently, Daridorexant decreases the wake drive, allowing sleep to occur awithout altering the sleep architecture.
Overseas phase III data has been published in The Lancet Neurology[1]: the pivotal studies demonstrated that Daridorexant significantly improved sleep onset, sleep maintenance, and self-reported total sleep time at the first and third month of treatment compared to placebo without altering the sleep architecture. The studies also showed that Daridorexant is safe and well-tolerated with no evidence of dependency, rebound insomnia, withdrawal symptoms, or drug abuse, which is significantly different from those reported with benzodiazepines.
In addition to improving the nighttime sleep of adults with chronic insomnia disorder, Daridorexant is also the only DORA approved by the European Medicines Agency (EMA) that has an impact on daytime functioning. Clinical data on Daridorexant are available for up to 12 months of continuous treatment, which can support the long-term medication.[2]
On November 15, 2022, Simcere entered into an exclusive license agreement with Idorsia and was granted an exclusive right to develop and commercialize Daridorexant in the Greater China region (Mainland China, Hong Kong, and Macau). Currently, Daridorexant has been approved in the United States, Great Britain, European Union, Switzerland and Canada. A New Drug Application ("NDA") has been filed in Japan recently. So far there is no DORA-type insomnia drug available in China.
The dosing of the first patient in the Chinese Phase III clinical study of Daridorexant is an important milestone of this innovative drug to help patients worldwide. Simcere will keep making every effort to conduct the subsequent Phase III clinical trial and look forward to making this new generation of more effective insomnia treatment widely accessible to insomnia patients with strong sleep needs in China.
Reference:
1.Mignot E, Mayleben D, Fietze I, Leger D, Zammit G, Bassetti CLA, et al. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol. 2022 Feb;21(2):125-139. Erratum in: Lancet Neurol. 2022 Jan 20; PMID: 35065036.
2.Kunz, D., Dauvilliers, Y., Benes, H. et al. Long-Term Safety and Tolerability of Daridorexant in Patients with Insomnia Disorder. CNS Drugs. 37, 93–106 (2023). https://doi.org/10.1007/s40263-022-00980-8.