Eisai Launches Dual Orexin Receptor Antagonist DAYVIGO® (lemborexant) for Insomnia in Hong Kong
Jul 07, 2021 03:33
CST Updated
03:33
Eisai
Pharmaceutical Product R&D and Manufacturer
July 6, 2021 /BioonBIOON/ -- Eisai recently announced that its subsidiary has launched a novel insomnia medication, Dayvigo (lemborexant), in Hong Kong, China. The drug is an orexin receptor antagonist discovered and developed internally by Eisai for the treatment of adult insomnia, a condition characterized by difficulty falling asleep and/or difficulty maintaining sleep. Dayvigo received regulatory approval in Hong Kong, China on February 28, 2021, marking its first commercial launch in Asia outside of Japan.
The active 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 chemical naturally produced by the hypothalamus that is involved in regulating the sleep-wake cycle.
The mechanism of action of Dayvigo in the treatment of insomnia is achieved through orexin receptor antagonism.The orexin neuropeptide signaling system plays a role in wakefulness. Blocking the binding of the wake-promoting neuropeptides orexin A and orexin B to orexin receptors OX1R and OX2R is believed to inhibit the drive for wakefulness. Dayvigo binds to orexin receptors OX1R and OX2R and acts as a competitive antagonist (IC50 values of 6.1 nM and 2.6 nM, respectively).
Dayvigo can provide patients with insomnia with faster sleep onset and improved sleep maintenance.The drug was approved by regulatory authorities in the United States and Japan in December 2019 and January 2020, respectively, and 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, Dayvigo 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, difficulty concentrating, and irritability. Insomnia is one of the most common sleep-wake disorders,
Approximately 30% of adults worldwide experience symptoms of insomnia. In Hong Kong, China, over 35% of adults report insomnia symptoms, with a notably higher prevalence among the elderly. Many patients endure symptoms that persist for months to years. Consequently, insomnia imposes various societal burdens, such as prolonged absenteeism and reduced work productivity, while also increasing the risk of falls among older adults.
Safety is a major concern with sleep medications. Earlier last year, the U.S.FDAA black box warning was issued for a class of insomnia medications (including Lunesta, Sonata, Ambien, etc.) following reports that dangerous activities such as sleepwalking and sleep-driving among some patients taking these drugs have resulted in injuries and fatalities.
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 treatment option for patients with insomnia.
Molecular structure of lemborexant (Image source: Wikipedia)
The Dayvigo insomnia clinical program includes two pivotal Phase III clinical studies, SUNRISE-1 (Study 304) and SUNRISE-2 (Study 303), enrolling approximately 2,000 patients.
——SUNRISE-1 Study: was a short-term (1-month) randomized, double-blind, placebo- and active-controlled trial conducted in 1,006 patients aged ≥55 years (45% of whom were aged ≥65 years) who had difficulty falling asleep at night, evaluating the efficacy and safety of lemborexant compared with placebo and the active control drug zolpidem tartrate extended-release.Data showed that the study met both the primary and secondary endpoints.: (1) Compared with placebo, Dayvigo 5 mg and 10 mg demonstrated statistically significant superiority in the primary efficacy endpoint, Latency to Persistent Sleep (LPS); (2) compared with placebo and the active control, Dayvigo 5 mg and 10 mg showed statistically significant improvements in Sleep Efficiency (SEF) and Wake After Sleep Onset (WASO). In this study, the most commonly reported adverse events in the lemborexant treatment groups were headache and somnolence.
——SUNRISE-2 Study: is a long-term (6-month) randomized, double-blind, placebo-controlled trial conducted in 949 adult patients (aged 18–88 years) with insomnia to evaluate the efficacy and safety of lemborexant compared with placebo.Data show that the study also met the primary endpoint and key secondary endpoints.: (1) Compared with placebo, Dayvigo 5 mg and 10 mg demonstrated statistically significant superiority in the primary efficacy endpoint of patient-reported subjective sleep onset latency (sSOL); (2) it also demonstrated statistically significant superiority in the sleep maintenance endpoints of patient-reported sleep efficiency (sSEF, defined as the proportion of time spent asleep while in bed) and wake after sleep onset (sWASO, defined as the number of minutes awake after sleep onset).
Analyses of both studies demonstrate that Dayvigo does not cause rebound insomnia, and there is no evidence of withdrawal effects upon discontinuation, indicating that physical dependence does not develop with up to one year of treatment. Dayvigo is the first to receive U.S.FDAApproved insomnia medication with 12 months of treatment safety data and 6 months of efficacy data for sleep onset and sleep maintenance in pivotal studies.
In the two studies, the most commonAdverse Reactions(Reported in ≥5% of Dayvigo-treated patients and at least twice the rate of placebo) is somnolence (Dayvigo 10 mg, 10%; Dayvigo 5 mg, 7%; placebo, 1%). (Bioon.com)