Clinical Impacts of New FDA-Approved Oveporexton for Narcolepsy Type 1: Sara Sarkey, PhD

WATCH TIME: 4 minutes

Narcolepsy type 1 (NT1) is a chronic sleep-wake disorder characterized by excessive daytime sleepiness, cataplexy, disrupted nighttime sleep, and other manifestations of REM sleep dysregulation. Central to its pathophysiology is the loss of orexin-producing neurons in the hypothalamus, resulting in deficient orexin signaling and an inability to maintain stable wake and sleep states.¹ Historically, treatment has relied on therapies directed toward individual manifestations of the disease rather than replacing the signaling lost in NT1.

On August 5, 2026, the FDA approved oveporexton (Orzeyful; Takeda), an oral selective orexin receptor 2 agonist, for adults with NT1.²Marketed as Orzeyful, the approval represented the first therapy to directly restore orexin signaling and treat NT1 as a complete disorder. In the phase 2 program, published in the New England Journal of Medicine, oveporexton produced significant improvements in objective wakefulness, patient-reported sleepiness, and cataplexy, findings that preceded the pivotal phase 3 FirstLight and RadiantLight studies supporting approval.^1,2

“I have talked to so many patients who have accepted ‘good enough.’ To me, it’s amazing to have something that could potentially improve that overall quality of life so that they can live the life they want to live and reach goals they may not have thought possible.”

Sara Sarkey, PhD, vice president of Neuroscience and Vaccines at Takeda, has been involved in the company's neuroscience portfolio as orexin-directed therapeutics have advanced from a longstanding biologic concept toward clinical application. Following the FDA decision, Sarkey sat down with NeurologyLive^® to provide perspective on what the approval may mean for the treatment of NT1.

In the interview, Sarkey discusses how directly addressing orexin deficiency could change expectations for clinicians and patients accustomed to managing NT1 symptom by symptom. She also considers the broader implications of treating a 24-hour disorder, the substantial adaptations patients often make around their symptoms, and why treatment goals may increasingly extend beyond conventional symptom measures toward everyday functioning and quality of life.

REFERENCES
1. Dauvilliers Y, Plazzi G, Mignot E, et al. Oveporexton, an oral orexin receptor 2-selective agonist, in narcolepsy type 1. N Engl J Med. 2025;392(19):1905-1916. doi:10.1056/NEJMoa2405847.
2. US Food and Drug Administration. FDA approves first drug to treat the full range of narcolepsy type 1 symptoms. Published August 5, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-full-range-narcolepsy-type-1-symptoms