New data presented by Takeda at SLEEP 2026 this week continues to build the case for oveporexton (TAK-861) as a potential disease-modifying treatment for narcolepsy type 1 (NT1). Oveporexton is designed to address the root cause of the disease, targeting the underlying orexin deficiency responsible for NT1.
Results from two pivotal studies showed that the investigational oral orexin receptor 2 (OX2R)-selective agonist improved daily functioning along with cognitive and sleep-related symptoms experienced by people with NT1.1,2,3
Combined with previously reported Phase 3 findings, the latest results suggest the therapy offers broad clinical benefits and could represent a significant shift in the treatment landscape for NT1.4
SleepWorld sat down with Elena Koundourakis, PhD, head of Takeda’s Orexin Franchise Development & Neuroscience Programs to talk about the impact of these findings:
“This drug really covers the total spectrum of the disease. It provides robust and clinically meaningful improvements in objective and subjective measurements across daytime and nighttime symptoms,” Dr. Koundourakis said. “It’s really quite exciting and doesn’t happen too many times in drug development.”
“We’re very excited that we were able to show this correlation between what we’re measuring objectively and how patients feel and function,” she said. “We are so thankful to the patients who really stuck with us. We had some setbacks with previous compounds, and they didn’t give up on us and we didn’t give up on them, and we are very excited to be here and share this moment with them.”
Here’s what Takeda reported:
“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,” said Emmanuel Mignot, M.D., Ph.D., principal investigator for the FirstLight (TAK-861-3001) 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, 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 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.5 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,” said Sarah Sheikh, M.Sc., B.M., B.Ch., MRCP, Head, Neuroscience Therapeutic Area Unit and Global Development at Takeda. “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 United States.
Source: Takeda
1. Plazzi G, Dauvilliers Y, Pizza F, et al. Effect of the Oral Orexin Receptor 2 Agonist Oveporexton (TAK-861) on Functional Impacts of Narcolepsy Type 1: Results from Two Phase 3 Studies. Presented at: SLEEP 2026; 14-17 June 2026; Baltimore, MD.
2. Pizza F, Dauvilliers Y, Del Rio Villegas R, et al. Oveporexton (TAK-861) Improves Cognitive Symptoms in Patients with Narcolepsy Type 1: Results from Two Randomized, Placebo-controlled Phase 3 Trials. Presented at: SLEEP 2026; 14-17 June 2026; Baltimore, MD.
3. Barateau L, Gong Y, Dauvilliers Y, et al. Effects of Treatment with Oveporexton, an Orexin Receptor 2 Agonist, on Sleep in People with Narcolepsy Type 1: Phase 3 Results. Presented at: SLEEP 2026; 14-17 June 2026; Baltimore, MD.
4. The topline results of these studies were shared on September 8, 2025, in “Takeda Presents Orexin Data from Landmark Oveporexton (TAK-861) Phase 3 Program in Narcolepsy Type 1 at World Sleep 2025.” 5 Crawford S, et al. Sleep 2024;47(suppl 1):A288.
