Evaluating the Impact of Oveporexton in Phase 3 Studies for Narcolepsy Type 1: Elena Koundourakis, PhD

WATCH TIME: 5 minutes | Captions are auto-generated and may contain errors.

“It's an interesting disease because it has symptoms both in the day and in the night, and it has been understood for a very long time that it's more like a disease that has been described by excessive daytime sleepiness as well as cataplexy."

Narcolepsy type 1 (NT1) is caused by the selective loss of orexin-producing neurons in the hypothalamus, a deficiency that drives the disorder's hallmark daytime and nighttime symptoms. Current treatments address individual symptoms but do not target this underlying mechanism. Oveporexton (Takeda), an investigational oral orexin receptor 2-selective agonist, is designed to restore orexin signaling directly. New pooled phase 3 data on the agent presented at the 2026 SLEEP Annual Meeting, held June 14-17 in Baltimore, Maryland, added to prior evidence supporting its potential as a mechanism-based therapy for NT1.¹

At the meeting, Takeda presented pooled results from the FirstLight (NCT06470828) and RadiantLight (NCT06505031) phase 3 studies, which evaluated twice-daily 2-mg and 1-mg doses of oveporexton against placebo. Overall, the pooled analysis showed statistically significant improvements across the 6 domains of the Functional Impacts of Narcolepsy Instrument (FINI), including tiredness, cognitive functioning, and everyday activities. New data presented at this meeting also included cognitive testing which correlated with patient-reported FINI cognitive scores, along with exploratory polysomnography findings showing a shift toward more normalized REM sleep architecture and reduced nighttime sleep disruption.

To dive deeper into these findings, NeurologyLive^® spoke with Elena Koundourakis, PhD, head of Orexin Franchise Development and Neuroscience Programs at Takeda. In the interview, Koundourakis outlined the design of the FirstLight and RadiantLight studies, walked through the correlation observed between objective and patient-reported cognitive measures, and detailed the newly presented nighttime sleep findings, including the shift toward more normalized REM sleep architecture on PSG. She also discussed why both daytime and nighttime results represent a meaningful step for the NT1 treatment landscape.

Click here for more coverage of SLEEP 2026.

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. Takeda. July 15, 2026. Accessed July 17, 2026. https://www.takeda.com/newsroom/newsreleases/2026/oveporexton-phase-3-narcolepsy-type-1/