China’s NMPA approves Takeda’s ORZEYFUL (oveporexton), the first oral orexin receptor 2 agonist for narcolepsy type 1, supported by positive Phase 3 FirstLight and RadiantLight trial results.
Written By: Fariha Sameen, BPharm
Reviewed By: Pharmacally Editorial Team
Takeda has received approval from China’s National Medical Products Administration (NMPA) for ORZEYFUL (oveporexton) to treat narcolepsy type 1 (NT1) in adolescents aged 16 years and older and adults. The approval makes oveporexton the first oral orexin receptor 2 (OX2R)-selective agonist approved in China and the country’s first approved medicine that targets the underlying cause of NT1, marking a major advance beyond conventional symptom-based therapies.
The approval follows positive results from Takeda’s global Phase 3 clinical program and expands the company’s neuroscience portfolio in China. Oveporexton is also under priority review in the United States after receiving Breakthrough Therapy designation and is under regulatory review in Japan with Sakigake designation. Additional global submissions are planned during the year.
First Orexin Agonist Targets the Cause of Narcolepsy Type 1
Narcolepsy type 1 is a chronic neurological disorder caused by the loss of orexin-producing neurons, resulting in orexin deficiency that disrupts the brain’s ability to regulate sleep and wakefulness. Unlike existing treatments that address individual symptoms, oveporexton selectively activates the orexin receptor 2 (OX2R) to restore orexin signaling.
By replacing the missing orexin activity, the therapy improves wakefulness while reducing rapid eye movement (REM) sleep-related symptoms, including cataplexy, a sudden loss of muscle tone that characterizes NT1.
China is estimated to have approximately 700,000 people living with narcolepsy, with 75% to 80% of cases classified as NT1. The disease typically develops between the ages of 10 and 20 and substantially affects education, employment, social functioning, and mental health. Delayed diagnosis remains common, often exceeding 10 years because of low disease awareness and diverse clinical manifestations.
Phase 3 Studies Demonstrated Broad Symptom Improvement
The approval is supported by the global Phase 3 FirstLight (TAK-861-3001; NCT06470828) and RadiantLight (TAK-861-3002; NCT06505031) studies.
Both multicenter, placebo-controlled trials evaluated the efficacy, safety, and tolerability of oveporexton over 12 weeks in patients with narcolepsy type 1 across 19 countries.
The FirstLight study enrolled 168 participants, who received twice daily oveporexton 2 mg, oveporexton 1 mg, or placebo. RadiantLight enrolled 105 participants randomized to twice-daily oveporexton 2 mg or placebo.
The primary endpoint in both trials was improvement in excessive daytime sleepiness measured by the Maintenance of Wakefulness Test (MWT). Secondary endpoints included the Epworth Sleepiness Scale (ESS), Weekly Cataplexy Rate (WCR), Narcolepsy Severity Scale for Clinical Trials (NSS-CT), Psychomotor Vigilance Test (PVT), Patient Global Impression of Change (PGI-C), Functional Impacts of Narcolepsy Instrument (FINI), 36-Item Short Form Survey (SF-36), and treatment-emergent adverse events.
The studies showed statistically significant improvements over placebo across prespecified endpoints, including reductions in excessive daytime sleepiness and cataplexy, together with improvements in multiple patient-reported and functional outcome measures.
Oveporexton demonstrated a safety profile consistent with previous clinical studies. The most frequently reported adverse events were insomnia, urinary urgency, and urinary frequency.
Experts Highlight Shift Beyond Symptom Management
Yan Liu, General Manager of Takeda China, said the approval addresses a major unmet medical need and reflects the accelerated regulatory review process that enabled earlier patient access in China. He added that the milestone also expands Takeda China’s presence into neuroscience.
Professor Han Fang, Director of the Sleep Medicine Center at Peking University People’s Hospital and Director of the Peking University Sleep Research Center, said the approval represents an important transition from managing individual symptoms toward a mechanism-based treatment approach capable of addressing multiple manifestations of narcolepsy type 1 while supporting improvements in daily functioning and quality of life.
Lin Wang, Head of Research and Development for Global Regions and Head of R&D China and Asia-Pacific at Takeda, noted that oveporexton was discovered and developed internally and represents the first approved orexin agonist for NT1 in China, reinforcing the company’s long-term investment in orexin biology.
Global Regulatory Reviews Continue
Following its first approval in China, oveporexton remains under priority review in the United States and regulatory review in Japan, with additional submissions planned across multiple regions during the year.
Takeda is also advancing a broader orexin portfolio that includes TAK-360, an oral OX2R agonist being studied for narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia, alongside TAK-495 and other investigational orexin agonists targeting sleep-wake disorders and additional neurological conditions.
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About the Writer
Fariha Sameen, PharmD (LinkedIn), is a clinical pharmacy professional with hands-on experience in patient counselling, medication review, therapeutic monitoring, and clinical documentation across multiple departments. She has experience identifying and assessing drug-related problems and supporting medication safety practices. Her interests include pharmacovigilance, ADR reporting, clinical research, and medical writing focused on clear, evidence-based communication.