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 set PDUFA date for the third quarter of 2026.¹

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 5-10, 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

“The FDA’s acceptance of our NDA is a milestone for people living with narcolepsy type 1,” Andrew Plump, MD, PhD, president of R&D at Takeda, said in a recent statement.¹ “Considering the high unmet need, this community deserves a new and different treatment approach that aims to address the underlying orexin deficiency that causes NT1 by restoring orexin signaling. We are one step closer to potentially transforming the current treatment paradigm and intend to deliver through our leading work in orexin science.”

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.

"The comprehensive assessments from our Phase 3 studies build on the transformative results we saw with our Phase 2b study with most participants reaching normative ranges and reporting clinically meaningful improvement across a broad range of symptoms at the end of the 12-week treatment period,” Plump, said in a prior statement.² "The positive results also reinforce the continued momentum for our late-stage pipeline, which we believe will deliver value to the patients we serve around the world."

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/