美国FDA批准莱博雷生(Dayvigo)用于治疗成人患者的失眠症

On December 23, 2019, Eisai Co., Ltd. announced that the U.S. Food and Drug Administration (FDA) approved its new drug application for the independently developed orexin receptor antagonist Dayvigo.

Dayvigo is approved for the treatment of insomnia in adults characterized by difficulty falling asleep and/or maintaining sleep. In the United States, Dayvigo will be available in 5 mg and 10 mg tablets.

The mechanism of action of Dayvigo

The mechanism of action of Dayvigo in treating insomnia characterized by difficulty falling asleep and/or maintaining sleep is through the antagonism of orexin receptors. The orexin neuropeptide signaling system plays a role in maintaining wakefulness. Blocking the binding of the wake-promoting neuropeptides orexin A and orexin B to the orexin receptors OX1R and OX2R is thought to inhibit wakefulness drive. Dayvigo can bind to the orexin receptors OX1R and OX2R, acting as a competitive antagonist, and has a stronger inhibitory effect on OX2R.

Clinical studies of Dayvigo

This approval is based on the results of a clinical development program, which included two pivotal Phase III studies (SUNRISE2 and SUNRISE1). The two studies evaluated Dayvigo versus a control drug for up to one month and versus placebo for up to six months in about 2,000 adults with insomnia. From these study results, Dayvigo demonstrated statistically significant advantages compared to placebo in both subjective and objective assessments of falling asleep and maintaining sleep.

In the SUNRISE2 and SUNRISE1 studies, rebound insomnia did not occur after discontinuation of Dayvigo, and there was no evidence of withdrawal effects after discontinuation of Dayvigo at both doses. Additionally, the development program included multiple safety studies that evaluated the drug's effects on postural stability, cognitive performance, driving performance and respiratory safety.

About Dayvigo

Dayvigo is a small molecule drug independently developed by Eisai. It can bind to the orexin receptors OX1R and OX2R and function as a competitive antagonist (its half inhibitory concentration (IC50) values ​​are 6.1nM and 2.6nM respectively). The mechanism of action of Dayvigo in treating insomnia is speculated to be through antagonizing orexin receptors. The orexin neuropeptide signaling system is related to the awake state. Blocking the binding of the wake-promoting neuropeptides orexin A and orexin B to the OX1R and OX2R receptors is thought to inhibit wakefulness drive.

Clinical study results show that the efficacy of leborexen is not only applicable to primary insomnia, but also to insomnia related to other diseases (such as depression) (SUNRISE-1 and SUNRISE-2 studies). In addition to the insomnia indication, a Phase II clinical trial of leborexan is ongoing in patients with ISWRD associated with mild to moderate Alzheimer's disease.