Takeda reports FirstLight, RadiantLight studies met all endpoints

Takeda (TAK) will present data from two global Phase 3 double-blind, placebo-controlled studies of oveporexton, a potential investigational oral orexin receptor 2-selective agonist in narcolepsy type 1, during multiple oral presentations at the World Sleep 2025 Congress in Singapore. Both the FirstLight and RadiantLight studies met all primary and secondary endpoints demonstrating statistically significant improvement across a broad range of NT1 symptoms compared to placebo with p-values of less than0.001 across all doses at week 12. Oveporexton was generally well-tolerated with a safety profile consistent across clinical studies to date. No serious treatment-related adverse events were reported. The most common adverse events were insomnia, urinary urgency and frequency. The studies investigated 14 primary and secondary endpoints over a total of 12 weeks in 273 patients across 19 countries. More than 95% of the participants who completed the studies enrolled in the ongoing long-term extension study. Oveporexton improved excessive daytime sleepiness demonstrating statistically significant improvement from baseline in mean sleep latency on the Maintenance of Wakefulness Test and in Epworth Sleepiness Scale scores at week 12 across doses compared to placebo. The majority of participants treated with the 2/2mg dose achieved wakefulness within normative range on the MWT, and close to 85% of participants achieved ESS scores comparable to healthy individuals. Oveporexton demonstrated significant reduction in weekly cataplexy rate over 12 weeks across doses compared to placebo. Median cataplexy free days compared to placebo improved from 0 days at baseline to 4-5 days per week at week 12. Cataplexy is a defining symptom for NT1 and is the sudden loss of muscle tone triggered by strong emotions. Oveporexton showed statistically significant changes from baseline in the narcolepsy severity scale total score compared to placebo with more than 70 percent of participants reporting the lowest severity level across doses. Oveporexton also resulted in statistically significant improvements in overall narcolepsy symptoms as assessed by the self-rated Patient Global Impression of Change scale with nearly all treated participants reporting improvements. Oveporexton resulted in statistically significant improvements in quality of life reaching scores in the normative range as assessed by the Short Form-36-item survey. These outcomes were supported by significant improvements on exploratory endpoints including the EuroQol 5-Dimension 5-Level. Across both studies, oveporexton was generally well-tolerated. No treatment-related serious adverse events were observed. Consistent with our experience from previous clinical studies, the most common adverse events were insomnia, urinary urgency and frequency. Most adverse events were mild to moderate.