TAK-861 · program
Oveporexton for Narcolepsy
- Breakthrough Therapy
- Priority Review
Oveporexton (TAK-861) is in regulatory review for narcolepsy type 1. Following positive Phase 3 FirstLight and RadiantLight pivotal studies, the FDA accepted Takeda's New Drug Application and granted Priority Review on 2026-02-10, with a PDUFA target action date in Q3 2026. The program holds FDA Breakthrough Therapy designation for excessive daytime sleepiness in NT1. NT1 is the lead indication of Takeda's orexin franchise.
Development timeline
- FDA accepted the oveporexton NDA for narcolepsy type 1 and granted Priority Review, with a PDUFA target action date in Q3 2026.↗
- metPhase 3 FirstLight and RadiantLight pivotal studies met all primary and key secondary endpoints (p<0.001) at week 12.↗
- metPhase 2b (TAK-861-2001) met primary MWT endpoint and key secondary endpoints (ESS, weekly cataplexy rate); results published in the New England Journal of Medicine.↗
Readouts
- 2026-02-10ReportedRegulatory
FDA accepted the oveporexton NDA for narcolepsy type 1 and granted Priority Review, with a PDUFA target action date in Q3 2026. ↗
- 2025-07-14ReportedTopline datametNCT06470828
Phase 3 FirstLight and RadiantLight pivotal studies met all primary and key secondary endpoints (p<0.001) at week 12. ↗
- 2025-05-14ReportedFull resultsmetNCT05687903
Phase 2b (TAK-861-2001) met primary MWT endpoint and key secondary endpoints (ESS, weekly cataplexy rate); results published in the New England Journal of Medicine. ↗
Clinical trials in Narcolepsy
NCT06505031TAK-861-3002Phase 3Completedn=105
RadiantLight: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-861 for the Treatment of Narcolepsy With Cataplexy (Narcolepsy Type 1)
metprimaryExcessive daytime sleepiness via Maintenance of Wakefulness Test (MWT) at week 12 — Clinically meaningful improvement with participants achieving near-normal ranges (<0.001)
Met primary MWT endpoint with statistically significant improvement vs placebo at week 12 (p<0.001). RadiantLight randomized 105 participants to high dose or placebo.
metsecondaryEpworth Sleepiness Scale (ESS) and Weekly Cataplexy Rate (WCR) at week 12 (<0.001)
All key secondary endpoints, including ESS and weekly cataplexy rate, were met with statistically significant improvement vs placebo at week 12 (p<0.001).
NCT06470828TAK-861-3001Phase 3Completedn=168
FirstLight: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-861 for the Treatment of Narcolepsy With Cataplexy (Narcolepsy Type 1)
metprimaryExcessive daytime sleepiness via Maintenance of Wakefulness Test (MWT) at week 12 — Clinically meaningful improvement with participants achieving near-normal ranges (<0.001)
Met primary MWT endpoint with statistically significant improvement vs placebo across all doses at week 12 (p<0.001). FirstLight randomized 168 participants to high dose, low dose, or placebo.
metsecondaryEpworth Sleepiness Scale (ESS) and Weekly Cataplexy Rate (WCR) at week 12 (<0.001)
All key secondary endpoints, including ESS and weekly cataplexy rate, were met with statistically significant improvement vs placebo across all doses at week 12 (p<0.001).
NCT05687903TAK-861-2001Phase 2Completedn=112
A Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-861 for the Treatment of Narcolepsy With Cataplexy (Narcolepsy Type 1)
metprimaryMean sleep latency on the Maintenance of Wakefulness Test (MWT) — Mean sleep latency reached values consistent with normative ranges in healthy individuals across all active doses (<=0.001)
Substantial, dose-spanning increases in mean MWT sleep latency vs placebo, sustained over 8 weeks (adjusted p <=0.001 for all comparisons).
metsecondaryEpworth Sleepiness Scale (ESS)
Significant reductions in ESS (excessive daytime sleepiness) across all doses vs placebo, sustained over 8 weeks.
metsecondaryWeekly Cataplexy Rate (WCR)
Significant reductions in weekly cataplexy rate across all doses vs placebo, sustained over 8 weeks.
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Oveporexton oral tablet 1 mg or 2 mg twice daily (Phase 3 FirstLight/RadiantLight); Phase 2 also tested 7 mg once daily | Oral | Twice daily | — |
Mechanism of action
Oveporexton is a potent, orally available, highly selective orexin receptor 2 (OX2R/HCRTR2) agonist with minimal activity at OX1R. By selectively activating OX2R on wake-promoting hypothalamic and brainstem neurons, it restores deficient orexin signaling in narcolepsy type 1, enhancing downstream monoaminergic and cholinergic wake-promoting pathways to increase wakefulness and suppress abnormal REM-sleep events such as cataplexy.
| Target | Action | Affinity |
|---|---|---|
| OX2RprimaryHCRTR2 | Agonist | —ⓘ |
← Full TAK-861 compound page (identity, identifiers, all indications)
Sources
- FirstLight: TAK-861 for the Treatment of Narcolepsy With Cataplexy (Narcolepsy Type 1) - Phase 3 (TAK-861-3001) — ClinicalTrials.gov
- NEJM Publication: Significant Improvements for Narcolepsy Type 1 in Phase 2b Trial of Oveporexton (TAK-861) — Takeda Pharmaceutical Company
- Oveporexton, an Oral Orexin Receptor 2-Selective Agonist, in Narcolepsy Type 1 (NEJM Phase 2; oral, once- and twice-daily dosing) — New England Journal of Medicine (PubMed)
- RadiantLight: TAK-861 for the Treatment of Narcolepsy With Cataplexy (Narcolepsy Type 1) - Phase 3 (TAK-861-3002) — ClinicalTrials.gov
- TAK-861 for the Treatment of Narcolepsy With Cataplexy (Narcolepsy Type 1) - Phase 2b (TAK-861-2001) — ClinicalTrials.gov
- Takeda Announces Positive Results from Two Pivotal Phase 3 Studies of Oveporexton (TAK-861) in Narcolepsy Type 1 (investigational oral OX2R agonist) — Takeda Pharmaceutical Company
- U.S. Food and Drug Administration Accepts New Drug Application and Grants Priority Review for Takeda's Oveporexton (TAK-861) as a Potential First-in-Class Therapy for Narcolepsy Type 1 — Takeda Pharmaceutical Company