Small Molecule · TAK-861
Oveporexton
- Breakthrough Therapy
- Priority Review
Oveporexton (TAK-861) is an oral, highly selective orexin receptor 2 (OX2R/HCRTR2) agonist developed by Takeda to address the underlying orexin (hypocretin) deficiency that causes narcolepsy type 1. By selectively activating OX2R on wake-promoting neurons, it enhances wakefulness and suppresses abnormal REM-sleep events such as cataplexy. It is the lead asset in Takeda's orexin franchise and is in late-stage development for NT1.
Also known as: TAK-861, Oveporexton, 2460722-04-5
- Modality
- Small molecule
- Chemical class
- pyrrolidine, ethanesulfonamide
- Chemistry
- Single enantiomer
- Mechanism
- OX2R agonist
- Highest phase
- Filed (NDA)
- Lead indication
- Narcolepsy
- Developer
- Takeda Pharmaceutical Company Limited (4502.T)
- Designations
- Breakthrough Therapy, Priority Review
- Trials
- 3 tracked
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 | —ⓘ |
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 | — |
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.↗
Oveporexton for Narcolepsy
Filed (NDA)ActiveNarcolepsy indication →
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.
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
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.
Conference coverage
TAK-861 appears in 1 CNS Pulse conference abstract:
Identifiers
- PubChem CID 154617563
- FDA UNII 59MF6P2ATF
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