At a Glance
- Eisai received orphan drug designation in Japan for E2086 for narcolepsy
- E2086 is a selective orexin 2 receptor agonist targeting wakefulness regulation
- Early Phase Ib data suggest potential improvement in daytime wakefulness
- Narcolepsy remains a high unmet medical need with 46,000 patients in Japan
Written By: Sana Khan BPharm
Reviewed By: Pharmacally Editorial Team
Eisai Co., Ltd. has received orphan drug designation in Japan for its investigational selective orexin 2 receptor agonist, E2086. The designation was granted by Japan’s Ministry of Health, Labour and Welfare.
Addressing a Persistent Unmet Need
Narcolepsy is a chronic neurological sleep disorder primarily characterized by excessive daytime sleepiness (EDS), often accompanied by fatigue, cognitive impairment, and significant functional limitations. Despite available therapies, many patients continue to experience residual symptoms, contributing to a substantial disease burden.
A recent 2025 estimate places the narcolepsy patient population in Japan at approximately 46,000 individuals. The disorder is broadly classified into two subtypes:
- Narcolepsy Type 1 (with cataplexy), associated with a deficiency of orexin due to autoimmune destruction of orexin-producing neurons in the hypothalamus
- Narcolepsy Type 2 (without cataplexy), where the underlying mechanism remains unclear but may involve reduced orexin neurotransmission
Orexin Pathway: From Sleep Promotion to Wake Stabilization
Orexin is a key neurotransmitter involved in regulating sleep-wake cycles. Suppression of orexin signaling promotes sleep, while activation supports wakefulness and stability of alertness.
Eisai has previously leveraged this pathway through DAYVIGO, an orexin receptor antagonist approved for insomnia treatment in more than 25 countries and regions. While DAYVIGO works by inhibiting orexin signaling to facilitate sleep, E2086 represents a mechanistically opposite strategy.
E2086 selectively activates orexin 2 receptors, aiming to enhance orexinergic signaling and directly target the underlying pathophysiology of narcolepsy.
Early Clinical Signals
Eisai recently presented findings from a Phase Ib clinical study involving patients with narcolepsy Type 1 at the World Sleep 2025 congress. The data suggested that E2086 may improve daytime wakefulness, a central therapeutic goal in narcolepsy management.
Although still in early-stage development, these results provide initial support for the drug’s potential clinical benefit.
Strategic Focus on Neurology and Sleep Disorders
Narcolepsy and other sleep-wake disorders remain a key focus within Eisai’s neurology portfolio. The orphan drug designation not only underscores the unmet medical need but may also provide regulatory incentives to accelerate clinical development.
With E2086, Eisai continues to expand its orexin-based platform, exploring both sleep-promoting and wake-stabilizing therapies within the same biological pathway.
If clinical development progresses successfully, E2086 could represent a novel, mechanism-driven option for patients living with narcolepsy, a condition that continues to challenge both patients and clinicians worldwide.
Reference
Ministry of Health, Labour and Welfare Grants Orphan Drug Designation in Japan to Novel Orexin Receptor Agonist E2086 for Narcolepsy, 16 February 2026, Ministry of Health, Labour and Welfare Grants Orphan Drug Designation in Japan to Novel Orexin Receptor Agonist E2086 for Narcolepsy | News ReleaseNews Release：2026 | Eisai Co., Ltd.