TAK-861 · program
Oveporexton for Narcolepsy
- Breakthrough Therapy
- Priority Review
Oveporexton (TAK-861) was approved by the FDA on 2026-08-05 as ORZEYFUL for narcolepsy type 1 in adults — the first medicine approved for NT1 as a complete disorder and the first acting on the orexin system. Approval followed the positive Phase 3 FirstLight and RadiantLight pivotal studies and a Priority Review granted 2026-02-10, and was preceded by China NMPA approval on 2026-07-22. FDA has recommended ORZEYFUL for scheduling under the Controlled Substances Act; it is lawful to market only after the DEA issues its scheduling decision. NT1 is the lead indication of Takeda's orexin franchise.
Development timeline
- FDA approved ORZEYFUL (oveporexton) tablets for narcolepsy type 1 in adults, on the basis of two randomized, double-blind, placebo-controlled 12-week studies in 273 adults. Approval was granted to Takeda Pharmaceuticals America, Inc. Marketing is lawful only after the DEA issues its Controlled Substances Act scheduling decision.↗
- metSLEEP 2026: FirstLight/RadiantLight secondary and exploratory endpoints (function via FINI, cognition, nighttime sleep/REM)↗
- Conference presentationSecondary and exploratory Phase 3 endpoint results for oveporexton presented at SLEEP 2026↗
- 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
- 2026-06-15ReportedFull resultsmet
SLEEP 2026: FirstLight/RadiantLight secondary and exploratory endpoints (function via FINI, cognition, nighttime sleep/REM) ↗
- 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)
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).
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.
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)
metsecondaryEpworth Sleepiness Scale (ESS)
Significant reductions in ESS (excessive daytime sleepiness) across all doses vs placebo, sustained over 8 weeks.
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).
metsecondaryWeekly Cataplexy Rate (WCR)
Significant reductions in weekly cataplexy rate across all doses vs placebo, sustained over 8 weeks.
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
- FDA Approves First Drug to Treat the Full Range of Narcolepsy Type 1 Symptoms — U.S. Food and Drug Administration
- 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
- 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 — Takeda Pharmaceutical Company
- Takeda: oveporexton Phase 3 secondary/exploratory endpoint data presented at SLEEP 2026 (FirstLight, RadiantLight) — Takeda Pharmaceutical Company Limited
- Takeda's ORZEYFUL (oveporexton) Approved in China as First Orexin Agonist and Only Medicine to Treat Narcolepsy Type 1 — Takeda Pharmaceutical Company Limited
- 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 Limited