Takeda’s ORZEYFUL (oveporexton) has been approved in Japan for adults with narcolepsy type 1, marking its third major global regulatory approval.
Written By: Kalyani Boharapi,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved ORZEYFUL (oveporexton) for the treatment of narcolepsy type 1 (NT1) in adults. Discovered in Takeda’s laboratories in Japan, ORZEYFUL is a first-in-class oral orexin receptor 2 (OX2R) agonist. It is the only medicine indicated in Japan to address the underlying orexin deficiency associated with NT1 rather than focusing solely on individual symptoms.
The approval marks the third major regulatory approval for ORZEYFUL globally, following approvals in the United States and China. In the U.S., ORZEYFUL is approved for adults with NT1, while its controlled-substance classification is currently under review by the U.S. Drug Enforcement Administration (DEA). In China, ORZEYFUL is approved for adolescents aged 16 years and older and adults with NT1. Takeda is proceeding with launch preparations in Japan and expects to make ORZEYFUL available as quickly as possible.
Addressing the Underlying Orexin Deficiency in NT1
NT1 is a chronic, rare neurological disease driven by orexin deficiency. It is associated with a broad range of daytime and nighttime symptoms, including excessive daytime sleepiness (EDS), cataplexy, disrupted nighttime sleep, sleep paralysis, hallucinations and cognitive symptoms. The persistent, 24-hour nature of the disease can significantly affect work, education and social interactions, while limited awareness and symptom complexity can contribute to diagnostic delays averaging more than 10 years.
As an OX2R agonist, ORZEYFUL selectively stimulates orexin receptor 2 to restore orexin signaling. By activating OX2Rs, it promotes wakefulness and reduces abnormal rapid eye movement (REM)-sleep-like phenomena, including cataplexy, addressing a range of daytime and nighttime symptoms evaluated in clinical studies.
Phase 3 Efficacy and Safety Profile
The approval was supported by global Phase 3 FirstLight and RadiantLight studies, which demonstrated statistically significant improvements across the full range of NT1 symptoms evaluated in the clinical trials compared with placebo. These included improvements in excessive daytime sleepiness, cataplexy and other secondary efficacy measures.
ORZEYFUL was generally well tolerated across the clinical development program, with a safety profile consistent across clinical studies conducted to date. The most commonly reported adverse events were:
- Insomnia
- Urinary urgency
- Urinary frequency
- Excessive saliva
Takeda’s Orexin Pipeline
Oveporexton is the lead OX2R agonist within Takeda’s broader orexin research and development portfolio. The company is investigating additional oral orexin agonists across multiple sleep-wake disorders and other indications in which orexin may play a role, including respiration, mood and metabolism.
Takeda is also investigating TAK-360 for NT1, narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH), as well as TAK-495.
Reference
About the Writer
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.