Takeda Presents Orexin Data from Landmark Oveporexton (TAK-861) Phase 3 Program in Narcolepsy Type 1 at World Sleep 2025

Core Insights - Takeda is presenting data on Oveporexton (TAK-861), an investigational oral orexin receptor 2 (OX2R)-selective agonist for narcolepsy type 1 (NT1), at the World Sleep 2025 Congress, highlighting its potential to transform treatment paradigms for this condition [1][21] - The Phase 3 studies demonstrated statistically significant improvements in NT1 symptoms, with p-values of <0.001 across all doses, indicating a strong efficacy profile [2][11] - Oveporexton was generally well-tolerated, with a safety profile consistent with previous studies, and no serious treatment-related adverse events reported [2][10] Group 1: Study Results - Both the FirstLight and RadiantLight studies met all primary and secondary endpoints, showing significant improvement in excessive daytime sleepiness and cataplexy [2][11] - Oveporexton improved excessive daytime sleepiness, with a majority of participants achieving normative wakefulness within 20 minutes on the Maintenance of Wakefulness Test (MWT) [10] - The median cataplexy-free days improved from 0 at baseline to 4-5 days per week at week 12, demonstrating a significant reduction in weekly cataplexy rates [10] Group 2: Quality of Life and Symptom Severity - Oveporexton resulted in over 70% of participants reporting mild severity levels on the narcolepsy severity scale, indicating a significant reduction in symptom severity [10] - Quality of life improvements were statistically significant, reaching normative scores on the Short Form-36-item (SF-36) survey [10] - Nearly all treated participants (97%) reported improvements in overall narcolepsy symptoms as assessed by the Patient Global Impression of Change (PGI-C) scale [10] Group 3: Future Developments - Takeda plans to submit global regulatory applications for Oveporexton starting in fiscal year 2025, leveraging its leadership in orexin science [1][12] - The Phase 3 program is one of the largest for NT1, involving 273 patients across 19 countries, with over 95% of participants enrolling in a long-term extension study [4][11] - Takeda is also exploring other orexin agonists for various conditions, indicating a robust pipeline in orexin-related therapies [12]