Takeda publishes oveporexton data in New England Journal of Medicine

Takeda (TAK) announced that the New England Journal of Medicine published data from the Phase 2b trial of oveporexton in people with narcolepsy type 1. Oveporexton is an investigational oral orexin receptor 2-selective agonist designed to restore orexin signaling to address the underlying orexin deficiency that causes NT1. Results demonstrated significant improvement in objective and subjective measures of excessive daytime sleepiness, reductions in cataplexy events and clinically meaningful improvements in disease severity and quality of life across all doses tested compared to placebo through eight weeks of treatment. The primary endpoint demonstrated substantial increases in mean sleep latency on the Maintenance of Wakefulness Test, a key measure of wakefulness, with improvements across all doses compared to placebo sustained over 8 weeks. The mean sleep latency on the MWT reached values consistent with normative values seen in healthy individuals. Key secondary endpoints demonstrated significant reductions in Epworth Sleepiness Scale scores, a measure of EDS, and reductions in Weekly Cataplexy Rate across all doses compared to placebo and were sustained over 8 weeks. The Narcolepsy Severity Scale for Clinical Trials, a self-assessment scale used to assess the severity, frequency and impact across narcolepsy symptoms, and the 36-item short-form, used to assess quality of life, were evaluated as exploratory endpoints. NSS-CT domain scores indicated marked improvements across most domains while clinically meaningful improvements in quality of life as assessed with the SF-36 questionnaire were observed with all oveporexton dose groups compared to placebo. The most commonly reported treatment-emergent adverse events were insomnia, increased urinary urgency and frequency. Most TEAEs were mild to moderate in intensity, and most started within 1-2 days of treatment and were transient. No cases of hepatotoxicity or visual disturbances were reported. The majority of participants who completed the trial enrolled in the long-term extension study, with many patients reaching one year or more of treatment. Takeda anticipates a data readout from the Phase 3 trials in calendar year 2025.