Takeda presented additional results from 2 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 signaling. These 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.

Emmanuel Mignot, MD, PhD, principal investigator for the FirstLight (TAK-861-3001) phase 3 study, said, "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. 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 2 global, multicenter, placebo-controlled studies—FirstLight (TAK-861-3001; twice-daily 2mg, 1mg and placebo) and RadiantLight (TAK-861-3002; twice-daily 2mg and placebo)—including:

• functioning: At all doses, oveporexton significantly improved daily functioning at week 12 compared to placebo (p<0.001) across the 6 domains of the Functional Impacts of Narcolepsy Instrument (FINI). Most patients reached or exceeded the published normative domain thresholds, underscoring oveporexton’s ability to allow individuals to manage their everyday lives. FINI reflects the domains that are of highest impact for NT1 including tiredness, cognitive functioning, cataplexy, social activities, everyday activities and everyday responsibilities.
• cognition: Oveporexton improved cognitive symptoms associated with NT1 compared to placebo, as measured using objective neuropsychological tests of attention, executive function and memory along with patient-reported measures. On the FINI Cognitive Function domain, approximately 70 percent of patients across all doses reported no significant cognitive difficulties compared to approximately 15 percent 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 and most patients on the 2/2mg dose reported meaningful reductions in disturbed nighttime sleep from baseline. Additionally, the timing and pattern of Rapid Eye Movement (REM) sleep shifted toward those seen in healthy controls.

Sarah Sheikh, MSc, BM, BCh, MRCP, Head, Neuroscience Therapeutic Area Unit and Global Development, Takeda, said, "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. We are grateful to the patients, caregivers and healthcare providers who have been a part of this journey. 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.”

Takeda will present additional data at the conference, including pooled analyses from previously presented phase 3 results, data evaluating the impact of oveporexton in reducing microsleeps and an evaluation of the holistic symptom impact of NT1 in the US.