Oveporexton, an Oral Orexin Receptor 2–Selective Agonist, in Narcolepsy Type 1

This phase 2, randomized, placebo controlled trial evaluated the efficacy and safety of oveporexton (TAK-861), an oral orexin receptor 2 (OX2R) selective agonist, in 112 participants with narcolepsy type 1. Over 8 weeks, oveporexton significantly improved wakefulness (mean increase in sleep latency on the Maintenance of Wakefulness Test: 12.5–25.4 minutes vs. 1.2 minutes with placebo; P≤0.001), reduced daytime sleepiness (Epworth Sleepiness Scale scores improved by 8.9 to 13.8 vs. 2.5), and decreased cataplexy episodes (weekly rate: 2.48–5.89 vs. 8.76; P<0.05 for higher doses). Common adverse events included insomnia (48%), urinary urgency (33%), and urinary frequency (32%), with no hepatotoxicity observed. Oveporexton demonstrated clinically meaningful improvements in narcolepsy symptoms with a favorable safety profile.

This phase 2, randomized, placebo controlled trial evaluated the efficacy and safety of oveporexton (TAK-861), an oral orexin receptor 2 (OX2R) selective agonist, in 112 participants with narcolepsy type 1. Over 8 weeks, oveporexton significantly improved wakefulness (mean increase in sleep latency on the Maintenance of Wakefulness Test: 12.5–25.4 minutes vs. 1.2 minutes with placebo; P≤0.001), reduced daytime sleepiness (Epworth Sleepiness Scale scores improved by 8.9 to 13.8 vs. 2.5), and decreased cataplexy episodes (weekly rate: 2.48–5.89 vs. 8.76; P<0.05 for higher doses). Common adverse events included insomnia (48%), urinary urgency (33%), and urinary frequency (32%), with no hepatotoxicity observed. Oveporexton demonstrated clinically meaningful improvements in narcolepsy symptoms with a favorable safety profile.