Japanese pharmaceutical company Eisai recently announced the launch of the new insomnia drug Dayvigo (lemborexant) CIV in the US market. The drug has 2 specifications (5mg and 10mg tablets) for the treatment of adult insomnia, which is a sleep awakening Disorders are characterized by difficulties in falling asleep and/or maintaining sleep despite adequate sleep opportunities. It is estimated that about 30% of adults worldwide have symptoms of insomnia, many of which last for months to years.
Dayvigo is a small molecule compound discovered and developed by Eisai. In the United States, Dayvigo received FDA approval in December 2019 for the treatment of insomnia in adults. In April of this year, the US Controlled (Special) Drug Administration (DEA) listed Dayvigo as a Schedule IV (Schedule IV) controlled drug. According to the definition in Schedule IV, patients with a history of abuse or addiction to alcohol or other drugs may have an increased risk of abuse and addiction to Dayvigo, and such patients should be carefully followed.
Dayvigo's active pharmaceutical ingredient is lemborexant, which is an orexin receptor antagonist that inhibits orexin signaling through competitive binding to orexin receptors (OX1R and OX2R). Orexin is a chemical substance naturally produced by the hypothalamus and is involved in sleep and wakefulness.
The mechanism of action of lemborexant in the treatment of insomnia is believed to be through antagonism of orexin receptors. The orexin neuropeptide signaling system plays a role in wakefulness. Blocking arousal promotes the binding of the neuropeptides orexin A and orexin B to the orexin receptors OX1R and OX2R, and is believed to inhibit arousal drive signals. lemborexant can bind to the orexin receptors OX1R and OX2R. As a competitive antagonist (IC50 values of 6.1 nM and 2.6 mM, respectively), the drug has a stronger inhibitory effect on OX2R.
It is estimated that insomnia affects one-third of adults. But because safety is a big problem with sleep medicine, new therapies face a difficult process in getting approval from doctors and patients. Earlier this year, the FDA implemented a black-box warning for a group of insomnia drugs such as Lunesta, Sonata, and Ambien because of reports that dangerous activities such as sleepwalking and sleep driving in patients taking these drugs caused casualties.
Due to the efficacy and safety issues, there are still significant unmet medical needs in the treatment of insomnia. Dayvigo is a product that can solve both the problem of sleep and the problem of sleep maintenance. The mechanism of action of this medicine will not damage the stability of posture and cognitive ability in the morning. The listing of Dayvigo will provide an important new treatment option for the group of insomniacs.
lemborexant molecular structure formula (Image source: Wikipedia)
Dayvigo was approved by the US FDA based on data from the lemborexant insomnia clinical development project, which included two key phase III clinical studies, SUNRISE-1 (304 study) and SUNRISE-2 (303 study), and enrolled approximately 2,000 patients. The SUNRISE-1 study was conducted in 1006 patients ≥55 years of age (45% of patients were ≥65 years of age) who had difficulty sleeping at night, and evaluated the efficacy of lemborexant relative to placebo and the positive control drug zolpidem tartrate sustained-release agent And safety, the data showed that the study reached the primary and secondary endpoints, and the most common adverse events reported by the lemborexant treatment group were headache and drowsiness. The SUNRISE-2 study was conducted in 949 adult (18-88 years old) patients with insomnia and evaluated the efficacy and safety of lemborexant relative to placebo. The data showed that the study also reached the primary endpoint and the critical secondary endpoint. The most common adverse events reported by the lemborexant treatment group were drowsiness, nasopharyngitis, headache and flu.
In addition to these key tests, Eisai has conducted some studies to further evaluate the safety of Dayvigo, including evaluating the effect of lemborexant on sound arousal, postural stability or memory the next day, and driving performance the next morning Research. The data shows that although lemborexant and placebo did not differ significantly in their ability to wake up sounds, lemborexant showed a dose-dependent deterioration in attention and memory compared to placebo. In addition, lemborexant did not differ significantly from placebo in postural stability or memory the next day. Although the 5mg and 10mg doses of lemborexant did not cause statistically significant damage to the driving performance of adult or elderly subjects the next morning (compared to the placebo), the driving performance in some subjects taking the 10mg dose of lemborexant Damaged.