Eisai's Dual Orexin Receptor Antagonist Dayvigo (Lemborexant) NDA Accepted in Hong Kong for Adult Insomnia

July 09, 2020 News /Bio ValleyBIOON/ -- Eisai recently announced that the New Drug Application (NDA) for its new insomnia medication, Dayvigo (lemborexant), has been accepted by the Department of Health of the Hong Kong Special Administrative Region of China. The drug is indicated for the treatment of adult insomnia characterized by difficulty falling asleep and/or difficulty maintaining sleep. This submission marks the first regulatory application for Dayvigo in Asia outside of Japan.

The active pharmaceutical ingredient of Dayvigo is lemborexant, a dual orexin receptor antagonist that inhibits orexin neurotransmission by competitively binding to the two subtypes of orexin receptors (OX1R and OX2R). Orexin is a naturally occurring chemical produced in the hypothalamus that plays a role in regulating the sleep-wake cycle. Blocking the binding of the wake-promoting neuropeptide orexin to its receptors is believed to balance the sleep-wake circuitry by suppressing excessive arousal drive. Dayvigo binds to orexin receptors OX1R and OX2R; as a competitive antagonist, it exhibits stronger inhibitory activity against OX2R.

Dayvigo can provide insomnia patients with faster sleep onset and better sleep maintenance. This drugis a type of drug discovered and developed internally by EisaiSmall Molecule CompoundsDayvigo was approved by regulatory authorities in the United States and Japan in December 2019 and January 2020, respectively, and was launched in these two markets in June and July 2020, respectively. In the United States, Dayvigo is available in two tablet strengths (5 mg and 10 mg); in Japan, it is available in three tablet strengths (2.5 mg, 5 mg, and 10 mg).

Insomnia is a sleep-wake disorder characterized by difficulty initiating and/or maintaining sleep despite adequate opportunity for sleep, resulting in daytime consequences such as fatigue, impaired concentration, and irritability. Insomnia is one of the most common sleep-wake disorders, with approximately 30% of adults worldwide experiencing symptoms of insomnia.

In Hong Kong, China, over 35% of adults experience symptoms of insomnia, with a higher prevalence among the elderly. Many patients suffer from insomnia symptoms that persist for months to years. Consequently, insomnia leads to various societal losses, such as prolonged absenteeism and reduced work productivity, and also increases the risk of falls in the elderly.

Safety is a major concern with sleep medications. Earlier this year, the United StatesFDABlack Box Warnings Issued for a Class of Insomnia Drugs (Including Lunesta, Sonata, and Ambien) Due to Reports of Injuries and Fatalities Resulting from Dangerous Activities Such as Sleepwalking and Sleep-Driving in Some Patients Taking These Medications

Dayvigo is a medication that addresses both sleep onset and sleep maintenance difficulties. Its mechanism of action does not impair morning postural stability or cognitive function. The launch of this product will provide an important new therapeutic option for patients with insomnia.

Molecular Structure of Lemborexant (Image source: Wikipedia)

The Dayvigo clinical development program for insomnia included two pivotal Phase III studies, SUNRISE-1 (Study 304) and SUNRISE-2 (Study 303), enrolling approximately 2,000 patients. The SUNRISE-1 study was conducted in 1,006 patients aged ≥55 years (45% of whom were aged ≥65 years) who had difficulty initiating sleep, and evaluated the efficacy and safety of lemborexant versus placebo and the active control zolpidem tartrate extended-release. The data showed that the study met its primary and secondary endpoints. The most commonly reported adverse events in the lemborexant treatment group were headache and somnolence. The SUNRISE-2 study was conducted in 949 adult patients (aged 18–88 years) with insomnia, and evaluated the efficacy and safety of lemborexant versus placebo. The data showed that this study also met its primary and key secondary endpoints. The most commonly reported adverse events in the lemborexant treatment group were somnolence, nasopharyngitis, headache, and influenza.

In addition to these pivotal trials, Eisai conducted further studies to evaluate the safety of Dayvigo, including assessments of lemborexant’s effects on auditory arousal capability, next-day postural stability and memory, and next-morning driving performance. The data indicated that although there was no significant difference between lemborexant and placebo in terms of auditory arousal capability, lemborexant was associated with dose-dependent impairments in attention and memory compared with placebo. Furthermore, no significant differences were observed between lemborexant and placebo regarding next-day postural stability or memory. Although 5 mg and 10 mg doses of lemborexant did not cause statistically significant impairment in next-morning driving performance in adult or elderly subjects compared with placebo, driving performance was impaired in some subjects receiving the 10 mg dose of lemborexant. (Bioon.com)

Original Source:New Drug Application For In-House Developed New Anti-Insomnia Drug Dayvigo Accepted In Hong Kong