Oveporexton Improves Daily Function, Cognition, and Nighttime Sleep in Narcolepsy Type 1

CONFERENCE REPORTER

Takeda presented additional results from 2 pivotal studies at the SLEEP 2026 Annual Meeting, showing oveporexton (TAK-861) improved daily functioning, cognition, and sleep-related symptoms associated with narcolepsy type 1 (NT1).^1-4

Oveporexton is an oral orexin receptor 2 (OX2R)-selective agonist that is designed to address the underlying orexin deficiency that causes NT1 by restoring orexin signaling. These data, along with previously shared phase 3 results, demonstrated improvement across the broad disease spectrum.

Psychiatric Times sat down with Elena Koundourakis, PhD, the head of the Orexin Franchise Development & Neuroscience Programs at Takeda, to learn more.

The SLEEP presentations highlighted results from secondary and exploratory endpoints from the 2 global, multicenter, placebo-controlled studies FirstLight (TAK-861-3001; twice-daily 2 mg, 1 mg, and placebo) and RadiantLight (TAK-861-3002; twice-daily 2 mg and placebo).

At all doses, oveporexton significantly improved daily functioning at week 12 compared with placebo (P<0.001) across the 6 domains of the Functional Impacts of Narcolepsy Instrument (FINI). Most participants reached or exceeded the published normative domain thresholds. FINI reflects the domains that are of highest impact for NT1, such as tiredness, cognitive functioning, cataplexy, social activities, everyday activities, and everyday responsibilities.

Oveporexton improved cognitive symptoms associated with NT1 compared with 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 participants across all doses reported no significant cognitive difficulties compared with approximately 15% of participants in the placebo arm.

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.

Dr Koundourakis is head of the Orexin Franchise Development and Portfolio Strategy at Takeda.

References

1. New pivotal study data show Takeda’s oveporexton improved daily function, cognition and nighttime sleep for people with narcolepsy type 1. News release. Monday June 15, 2026. Accessed June 17, 2026. https://www.takeda.com/newsroom/newsreleases/2026/oveporexton-phase-3-narcolepsy-type-1/

2. 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. Poster presented at: SLEEP 2026; June 14-17, 2026; Baltimore, MD.

3. Pizza F, Dauvilliers Y, Del Rio Villegas R, et al. Oveporexton (TAK-861) improves cognitive symptoms in patients with narcolepsy type 1: tesults from two randomized, placebo-controlled phase 3 trials. Poster presented at: SLEEP 2026; June 14-17, 2026; Baltimore, MD.

4. 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. Poster presented at: SLEEP 2026; June 14-17, 2026; Baltimore, MD.