Takeda reported new pivotal study results showing that its oral orexin receptor 2 agonist, oveporexton (TAK-861), improved daily functioning, cognition and nighttime sleep in people with narcolepsy type 1 (NT1). Oveporexton is designed to restore orexin signaling and address the underlying orexin deficiency that drives NT1, and the latest data, together with previously disclosed Phase 3 results, demonstrate improvement across the broad disease spectrum, supporting its potential to redefine the standard of care if approved.
Findings presented at SLEEP 2026 came from two global, multicenter, placebo-controlled studies in adults with NT1 evaluating twice-daily oveporexton (2 mg and 1 mg) versus placebo. Across all doses, oveporexton significantly improved daily functioning at week 12 compared with placebo (p<0.001) on all six domains of the Functional Impacts of Narcolepsy Instrument (FINI)—tiredness, cognitive functioning, cataplexy, social activities, everyday activities and everyday responsibilities. Most patients on oveporexton reached or exceeded published normative thresholds on these domains, suggesting a meaningful ability to better manage day-to-day life.
The drug also improved cognitive symptoms associated with NT1. Objective neuropsychological tests showed benefits in attention, executive function and memory, while patient-reported outcomes on the FINI Cognitive Function domain indicated that around 70% of patients receiving oveporexton at any dose reported no significant cognitive difficulties, compared with about 15% in the placebo arm.
Exploratory sleep endpoints showed that oveporexton improved nighttime sleep quality. Across doses, most treated patients reported no hallucinations or sleep paralysis, and those on the 2 mg twice-daily regimen reported meaningful reductions in disturbed nighttime sleep from baseline. The timing and pattern of rapid eye movement sleep also shifted toward those observed in healthy controls, consistent with more normalized sleep architecture.
Takeda said the comprehensive Phase 3 program was intentionally built to capture the full 24-hour burden of NT1, which extends beyond excessive daytime sleepiness and cataplexy to include cognitive and nocturnal symptoms. With oveporexton now under review by multiple regulatory agencies, the company believes it is close to delivering the first and only orexin agonist for the NT1 community and plans additional presentations at SLEEP 2026, including pooled Phase 3 analyses, microsleep data and an assessment of overall symptom burden in U.S. patients.
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