Oveporexton Improved Function, Cognition, and Sleep Outcomes in Narcolepsy Type 1.

Treatment with oveporexton (TAK-861; Takeda, Osaka, Japan and Cambridge, MA), an investigational oral orexin receptor 2–selective agonist, was associated with improved daily functioning and cognitive and sleep-related outcomes in people with narcolepsy type 1 (NT1). The findings, drawn from secondary and exploratory end points in the FirstLight (TAK-861-3001; NCT06470828) and RadiantLight (TAK-861-3002; NCT06505031) pivotal phase 3 studies, were presented at SLEEP 2026.

Oveporexton is designed to restore orexin signaling in NT1, a disorder characterized by orexin deficiency. FirstLight and RadiantLight were global, multicenter, placebo-controlled phase 3 studies evaluating the efficacy, safety, and tolerability of oveporexton over 12 weeks. FirstLight enrolled 168 participants randomized to receive twice-daily oveporexton 2 mg, oveporexton 1 mg, or placebo. RadiantLight enrolled 105 participants randomized to receive twice-daily oveporexton 2 mg or placebo.

Additional Phase 3 Findings

• Oveporexton treatment was linked to significant improvements in daily functioning at week 12 compared with placebo across all doses evaluated (P<.001), as measured by the Functional Impacts of Narcolepsy Instrument.
• Improvements were reported across 6 Functional Impacts of Narcolepsy Instrument domains: tiredness, cognitive functioning, cataplexy, social activities, everyday activities, and everyday responsibilities.
• Cognitive symptoms improved compared with placebo on objective neuropsychological tests of attention, executive function, and memory, as well as on patient-reported measures.
• On the cognitive function domain of the Functional Impacts of Narcolepsy Instrument, approximately 70% of participants receiving oveporexton across all doses reported no significant cognitive difficulties compared with approximately 15% of participants receiving placebo.
• Exploratory end points showed improvements in sleep quality across both studies. Most participants receiving oveporexton reported no hallucinations or sleep paralysis, and most participants receiving the 2-mg twice-daily dose reported meaningful reductions in disturbed nighttime sleep from baseline.
• The timing and pattern of rapid eye movement sleep shifted toward patterns observed in healthy controls.

Takeda previously reported phase 3 results for primary and key secondary outcomes from the oveporexton program. More than 95% of participants who completed FirstLight or RadiantLight enrolled in an ongoing long-term extension study.

According to an announcement from Takeda, the Food and Drug Administration (FDA) has accepted the company’s New Drug Application for oveporexton and granted Priority Review, with a Prescription Drug User Fee Act goal date in the third quarter of 2026.

Source

Takeda. New pivotal study data show Takeda’s oveporexton improved daily function, cognition and nighttime sleep for people with narcolepsy type 1. Published June 15, 2026. Accessed June 16, 2026. https://www.takeda.com/newsroom/newsreleases/2026/oveporexton-phase-3-narcolepsy-type-1/