Phase 3 data presented at SLEEP 2026 show the investigational orexin agonist improved daily functioning, cognition, and nighttime sleep in patients with narcolepsy type 1.
Key takeaways:
- Oveporexton (TAK-861) demonstrated significant improvements in daily functioning, cognition, and nighttime sleep for patients with narcolepsy type 1 across two phase 3 trials.
- Approximately 70% of patients across all oveporexton doses reported no significant cognitive difficulties, compared to about 15% in the placebo group.
Takeda presented additional results from two pivotal studies at SLEEP 2026, showing that 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).
“Narcolepsy type 1 is a 24-hour disease driven by orexin deficiency, and while excessive daytime sleepiness and cataplexy are the most recognized symptoms, many people experience additional bothersome symptoms such as cognitive difficulties and disrupted nighttime sleep,” says Emmanuel Mignot, MD, PhD, principal investigator for the FirstLight Phase 3 study, in a release. “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, multicenter, placebo-controlled studies—FirstLight (twice-daily 2mg, 1mg, and placebo) and RadiantLight (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 six 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% 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 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.
“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,” says Sarah Sheikh, MSc, BM, BCh, MRCP, head, neuroscience therapeutic area unit and global development at Takeda, in a release. “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.”
The US Food and Drug Administration accepted the New Drug Application and granted Priority Review for oveporexton, with a Prescription Drug User Fee Act goal date in the third quarter of this calendar year.
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 United States.
