Takeda has presented additional results from two pivotal studies at SLEEP 2026, showing oveporexton (TAK-861), an oral orexin receptor 2 (OX2R)-selective agonist, improved daily functioning as well as cognitive and sleep-related symptoms associated with narcolepsy type 1 (NT1).
Oveporexton is designed to address the underlying orexin deficiency that causes NT1 by restoring orexin signalling. The data, along with previously disclosed phase 3 results, demonstrated improvement across the broad disease spectrum, supporting the potential of oveporexton to redefine the standard of care for NT1.
“Narcolepsy type 1 is a 24-hour disease driven by orexin deficiency, and while excessive daytime sleepiness and cataplexy are the most recognised symptoms, many people experience additional bothersome symptoms such as cognitive difficulties and disrupted nighttime sleep,” said Emmanuel Mignot, principal investigator for the FirstLight phase 3 study. “Oveporexton has demonstrated significant improvement across a broad range of NT1 symptoms, daily functioning and quality of life with the potential to shift disease management beyond incremental symptom relief.”
The presentations highlighted results from secondary and exploratory endpoints from two global, multicentre, placebo-controlled studies, FirstLight and RadiantLight, including:
Functioning: at all doses, oveporexton significantly improved daily functioning at week 12 compared to placebo across the six domains of the Functional Impacts of Narcolepsy Instrument (FINI).
Cognition: oveporexton improved cognitive symptoms associated with NT1 compared to placebo. Approximately 70% of patients across all doses reported no significant cognitive difficulties compared to approximately 15% of patients in the placebo arm.
Nighttime Sleep: exploratory endpoints demonstrated that oveporexton improved quality of sleep across both studies. Across all doses, most patients reported no hallucinations or sleep paralysis.
“Narcolepsy type 1 is not defined by a single symptom, which is why we designed a comprehensive Phase 3 program to evaluate the effect of oveporexton on the broad disease impact,” said Sarah Sheikh, Head, Neuroscience Therapeutic Area Unit and Global Development at Takeda. “With oveporexton under review by multiple regulatory agencies, we are on the cusp of bringing the first and only orexin agonist to the narcolepsy type 1 community, with the potential to redefine the standard of care if approved.”