FDA Accepts New Drug Application for Orexin Agonist Oveporexton in Narcolepsy Type 1, Grants Priority Review

According to a new announcement, the FDA has accepted Takeda’s new drug application (NDA) and granted priority review to oveporexton, investigational oral orexin receptor 2 (OX2R)–selective agonist, for the treatment of patients with narcolepsy type 1 (NT1). The agent, designed to address the underlying orexin deficiency that causes NT1 by restoring orexin signaling, has a Prescription Drug User Fee Act action date set for the third quarter of 2026.¹

“Narcolepsy type 1 is a relentless disease that can have a debilitating impact on a person’s everyday life from work and school to social interactions. The currently available treatments offer symptom relief, but don’t address the underlying cause of the disease,” Andrew Plump, MD, PhD, president of research and development at Takeda, told NeurologyLive®. “Our investigational therapy oveporexton is designed to do just that by restoring orexin signaling. If approved, it would offer people living with narcolepsy type 1 and their health care providers a new approach to the way we treat this disease." 

The NDA is supported by positive data from global phase 3 studies FirstLight (NCT06470828) and RadiantLight (NCT06505031), which showed that oveporexton, formally known as TAK-861, met all its primary and secondary end points. FirstLight and RadiantLight, 2 multicenter, placebo-controlled studies, featured 168 and 105 patients with NT1, respectively, using change in Maintenance Wakefulness Test (MWT) as the primary end point.²

Conducted across 19 countries, FirstLight included high-dose, low-dose, and placebo arms, whereas RadiantLight included only high-dose and placebo arms. Presented at the 2025 World Sleep Congress, held September 5 to 10, 2025, in Singapore, findings showed that treatment with oveporexton in the 12-week trials led to statistically significant improvements in excessive daytime sleepiness reflected in MWT change, relative to placebo (P <.001).³

READ MORE: FDA Grants Orexin Agonist Alixorexton Breakthrough Therapy Designation for Narcolepsy Type 1

At the conclusion of the 12-week studies, oveporexton also showed statistically significant improvements in secondary outcomes, which included change in Epworth Sleepiness Scale and Weekly Cataplexy Rate (both P <.001). In addition, treatment with the investigational agent led to reported enhancements in ability to maintain attention, overall quality of life, and daily life functions, further supporting the drug’s development.

According to Takeda, oveporexton demonstrated a well-tolerated safety profile in the phase 3 studies, which mirrored what had been previously observed. The most common adverse events (AEs) included insomnia and urinary urgency and frequency, with no serious treatment-related AEs found. Of note, more than 95% of the study participants completed their treatment cycles and moved on to the ongoing long-term extension.

“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,” principal investigator for the FirstLight phase 3 study Emmanuel Mignot, MD, PhD, who serves as the Craig Reynolds Professor of Sleep Medicine in the Department of Psychiatry and Behavioral Sciences at Stanford University, said in a statement.³ “Takeda’s groundbreaking efforts targeting the orexin receptor 2 in clinical studies led to positive Phase 3 results for oveporexton, bringing us a major step closer to having the first orexin therapy that addresses the underlying cause of narcolepsy type 1—with the potential of transforming the current treatment paradigm.”

Results from the company's phase 2b study (NCT05687903) of oveporexton, published in the New England Journal of Medicine, showed promising efficacy in NT1.⁴ The trial featured 112 patients with NT1 aged 18 to 70 years randomly assigned to 1 of 4 dosing arms (twice-daily 0.5/0.5 mg, 2/2 mg, or 2/5 mg, or once-daily 7 mg) or placebo for 8 weeks. At the conclusion of the 8-week study, investigators recorded mean MWT changes of 12.5, 23.5, 25.4, and 15.0 minutes, respectively, for the oveporexton groups, vs changes of –1.2 for placebo (adjusted P ≤.001 for all comparisons).

The investigational agent also showed promising data across secondary end points as well. After 8 weeks of treatment, researchers reported mean ESS total score changes of –8.9, –13.8, –12.8, –11.3, and –2.5, respectively (adjusted P ≤.004 for all comparisons vs placebo). In addition, the weekly incidence of cataplexy at week 8 was 4.24, 3.14, 2.48, 5.89, and 8.76, respectively (adjusted P <.05 for 2 mg twice daily and 2 mg followed by 5 mg daily vs. placebo), favoring oveporexton.

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REFERENCES
1. U.S. Food and Drug Administration accepts new drug application and grants priority review for Takeda’s oveporexton (TAK-861) as a potential first-in-class therapy for narcolepsy type 1. News release. Takeda. February 10, 2026. Accessed February 11, 2026. https://www.takeda.com/newsroom/newsreleases/2026/fda-accepts-nda-priority-review-oveporexton-narcolepsy-type-1/
2. Takeda announces positive results from two pivotal phase 3 studies of oveporexton (TAK-861) in narcolepsy type 1. News release. Takeda. July 14, 2025. Accessed February 11, 2026. https://www.takeda.com/newsroom/newsreleases/2025/positive-results-phase-3-oveporexton-narcolepsy-type-1/
3. Takeda presents Orexin Data from Landmark Oveporexton (TAK-861) Phase 3 Program in Narcolepsy Type 1 at World Sleep 2025. News release. Takeda. September 8, 2025. Accessed February 11, 2026. https://www.takeda.com/newsroom/newsreleases/2025/takeda-orexin-data-oveporexton-phase-3-narcolepsy-world-sleep-2025/
4. The New England Journal of Medicine publishes data from phase 2b trial of oral orexin receptor 2 agonist oveporexton (TAK-861) in people with narcolepsy type 1. News release. Takeda. May 14, 2025. Accessed February 11, 2026. https://www.takeda.com/newsroom/newsreleases/2025/oveporexton-phase2b-trial-results/