FDA Approves Oveporexton (Orzeyful) for Narcolepsy Type 1

The US Food & Drug Administration (FDA) has approved oveporexton (Orzeyful) tablets for narcolepsy type 1 in adults, the first medicine to directly target orexin signaling loss and address the disorder as a complete condition.¹

Existing narcolepsy type 1 therapies, including stimulants and sedatives, manage individual symptoms without addressing the underlying orexin deficiency driving the disorder. Oveporexton is the first agent to activate the OX2R receptor directly, restoring the signal lost when orexin-producing neurons are destroyed. The approval was granted to Takeda Pharmaceuticals America, Inc, following Breakthrough Therapy Designation and Priority Review.¹

“For too long, people with narcolepsy type 1 have had to manage a complex, lifelong neuropsychiatric condition with treatments that only address pieces of it,” said Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA Center for Drug Evaluation and Research, in a statement. “This new drug is the first medicine that impacts the underlying biology of the disease, treating narcolepsy type 1 as a whole.”¹

Oveporexton Efficacy in FirstLight and RadiantLight

The approval rests on 2 randomized, double-blind, placebo-controlled 12-week trials enrolling 273 adults with narcolepsy type 1, FirstLight (NCT06470828, n = 168) and RadiantLight (NCT06505031, n = 105).2 FirstLight, conducted across 19 countries, included high-dose, low-dose, and placebo arms, while RadiantLight tested only the high-dose regimen against placebo.³ Both trials assessed oveporexton dosed at 1 mg or 2 mg twice daily, using change in Maintenance Wakefulness Test score as the primary endpoint.³

Across both studies, patients receiving oveporexton 2 mg showed significant improvements in their ability to stay awake during the day compared with placebo (P <.001).¹ Patients also reported substantially less daytime sleepiness and a significant reduction in cataplexy episodes.¹ Data presented at the 2025 World Sleep Congress showed both trials met all primary and secondary endpoints, with improvements reaching near-normal ranges by week 12.²

Oveporexton Safety and Secondary Endpoints

Beyond wakefulness, oveporexton produced meaningful improvement across the full spectrum of narcolepsy type 1 symptoms, including sleep paralysis, hallucinations, and disrupted nighttime sleep.¹

The most common adverse events were insomnia, increased urinary frequency, urgency to urinate, and increased saliva production, with a low rate of discontinuation due to side effects.¹ Oveporexton should not be co-administered with strong CYP3A inhibitors, and safety and effectiveness have not been established in patients under 18 years.¹ The drug has been recommended for scheduling under the Controlled Substances Act and will require a DEA scheduling decision before marketing begins.¹

"Our research has shown that the loss of orexin is the cause of narcolepsy type 1, which results in symptoms like excessive daytime sleepiness and cataplexy," said FirstLight investigator Emmanuel Mignot, MD, PhD, Craig Reynolds Professor of Sleep Medicine at Stanford University, in a statement.³

Orzeyful was previously approved in China in July 2026 as the first orexin agonist and only approved medicine for NT1, and Takeda has additional orexin agonists in development for narcolepsy type 2 and idiopathic hypersomnia.⁴ Marketing in the US remains contingent on the DEA's final scheduling decision under the Controlled Substances Act.¹

References

1. FDA Approves First Drug To Treat The Full Range Of Narcolepsy Type 1 Symptoms. U.S. Food and Drug Administration. Published August 5, 2026. Accessed August 5, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-full-range-narcolepsy-type-1-symptoms

2. Ciccone I. FDA accepts new drug application for orexin agonist oveporexton in narcolepsy type 1, grants priority review. NeurologyLive. Published February 11, 2026. Accessed August 5, 2026. https://www.neurologylive.com/view/fda-accepts-nda-orexin-agonist-oveporexton-nt1-grants-priority-review

3. Takeda Presents Orexin Data From Landmark Oveporexton (TAK-861) Phase 3 Program in Narcolepsy Type 1 at World Sleep 2025. Takeda. Published September 8, 2025. Accessed August 5, 2026. https://www.takeda.com/newsroom/newsreleases/2025/takeda-orexin-data-oveporexton-phase-3-narcolepsy-world-sleep-2025/

4. Takeda's ORZEYFUL (Oveporexton) Approved in China as First Orexin Agonist and Only Medicine to Treat Narcolepsy Type 1. Takeda. Published July 22, 2026. Accessed August 5, 2026. https://www.takeda.com/newsroom/newsreleases/2026/orzeyful-approved-china-narcolepsy/