YZJ-1139 · program
Fazamorexant (YZJ-1139) for Insomnia
Lead and sole indication. Approved in China: on 2026-05-21 the NMPA granted marketing approval for fazamorexant tablets (brand 孟平 / Mengping; MAH Jiangsu Haian Pharmaceutical, a wholly-owned Yangtze River Pharmaceutical Group subsidiary) for adult insomnia characterized by difficulty falling asleep and/or difficulty maintaining sleep — a Class 1 innovative chemical drug and the first domestically developed dual orexin receptor antagonist in China (the third DORA on the Chinese market after imported lemborexant and daridorexant). Approval rests on the pivotal Phase 3 study YZJ-1139-3-01 (NCT05525637; 1,037 enrolled / 1,034 randomized per the company, 20 mg and 40 mg vs placebo; co-primary subjective and polysomnographic sleep efficiency at 14 days), whose results premiered at World Sleep 2025 in Singapore: significant improvement in objective and subjective sleep parameters within 14 days, efficacy sustained over 6 months of continuous use, 0.6% discontinuation for adverse events, and no rebound insomnia or withdrawal signs on stopping. A 4-week Phase 3 active-controlled PSG study vs zolpidem 10 mg (NCT06975514) completed 2025-08. Approval is China-only; no US or EU filing identified as of 2026-08.
Development timeline
- NDA for fazamorexant submitted to the NMPA Center for Drug Evaluation (CDE). Date is an UPPER BOUND: the company's World Sleep Congress 2025 release (2025-09-21) states the NDA 'has been officially submitted'; one Chinese trade report (pharnexcloud) gives NDA acceptance as January 2025, which could not be confirmed against a primary source, so the earlier date is noted but not asserted.↗
- metPivotal Phase 3 (YZJ-1139-3-01, 1,034 randomized) results premiered at World Sleep 2025: significant improvement in objective and subjective sleep parameters within 14 days, sustained over 6 months; 0.6% AE discontinuation, no rebound insomnia or withdrawal.↗
- Pivotal Phase 3 study YZJ-1139-3-01 (NCT05525637) started: randomized, double-blind, placebo-controlled, multicenter study of 20 mg and 40 mg once nightly in insomnia disorder; 1,037 enrolled. Primary completion 2023-07-07.
- Phase 2 dose-ranging study YZJ-1139-2-01 (NCT06680505) started in primary chronic insomnia disorder: 300 patients, 10/20/40/60 mg vs placebo, multicenter, double-blind. Completed 2020-09-30. Registered on ClinicalTrials.gov retrospectively.
- First-in-human study YZJ-1139-1-01 (NCT06673927) started: single ascending doses 2-80 mg and multiple ascending doses 10-60 mg x 7 days in 104 healthy Chinese adults. Registered on ClinicalTrials.gov retrospectively (posted 2024); start date is the actual conduct date.
Readouts
- 2026-05-21ReportedRegulatorymet
NMPA approved fazamorexant tablets (孟平 / Mengping) for adult insomnia — the first domestically developed Chinese DORA. ↗
- 2025-09-10ReportedFull resultsmetNCT05525637
Pivotal Phase 3 (YZJ-1139-3-01, 1,034 randomized) results premiered at World Sleep 2025: significant improvement in objective and subjective sleep parameters within 14 days, sustained over 6 months; 0.6% AE discontinuation, no rebound insomnia or withdrawal. ↗
Clinical trials in Insomnia
NCT06975514YZJ-1139-3-02Phase 3Completedn=61
A Randomized, Double-blind, Active-controlled, Parallel-group Clinical Study to Evaluate the Efficacy and Safety of YZJ-1139 Tablets in the Treatment of Insomnia Disorder
NCT06680531YZJ-1139-1-14Phase 1Completedn=24
A Clinical Study to Evaluate the Drug Interaction Between YZJ-1139 Tablets and Escitalopram Oxalate Tablets
NCT06671470YZJ-1139-1-13Phase 1Completedn=27
Drug Interaction Study of YZJ-1139 Tablets With Ticagrelor Tablets
NCT06671444YZJ-1139-1-12Phase 1Completedn=16
Pharmacokinetics and Safety Study of YZJ-1139 in Subjects With Severe Renal Impairment and Normal Renal Function
NCT06671509YZJ-1139-1-11Phase 1Completedn=24
A Phase 1 Open-Label Single-Dose Study to Assess the Pharmacokinetics and Safety of YZJ-1139 in Subjects With Mild, Moderate and Normal Hepatic Impairment
metotherSingle-dose PK in mild/moderate hepatic impairment vs healthy controls (with PBPK modeling)
Published open access in Frontiers in Pharmacology 2026 with physiologically based pharmacokinetic modeling of fazamorexant in Chinese patients with hepatic impairment and healthy controls.
NCT05525637YZJ-1139-3-01Phase 3Completedn=1037
A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of YZJ-1139 Tablets in the Treatment of Insomnia Disorder
metprimaryCo-primary: change from baseline in subjective sleep efficiency (sleep diary) and polysomnographic sleep efficiency after 14 days
Per the company's World Sleep 2025 presentation (1,034 randomized; 20 mg and 40 mg vs placebo): both objective (PSG) and subjective sleep parameters significantly improved within 14 days — reduced sleep-onset latency, fewer nighttime awakenings, improved sleep efficiency — with efficacy sustained over 6 months of continuous use. No numeric effect sizes have been published in an open peer-reviewed source, so none are recorded.
metsafetySafety and tolerability — 0.6% discontinuation due to adverse events
Company-reported: only 0.6% of patients discontinued for adverse events; no rebound insomnia and no withdrawal symptoms observed after stopping treatment.
NCT06680505YZJ-1139-2-01Phase 2Completedn=300
A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Phase II Clinical Study to Evaluate the Efficacy and Safety of YZJ-1139 Tablets in the Treatment of Primary Chronic Insomnia Disorder
NCT06685341YZJ-1139-1-02Phase 1Completedn=20
PK/PD Study of YZJ-1139 (zolpidem and placebo comparator)
metotherBalance (body sway) and cognition at hypnotic doses vs zolpidem 10 mg and placebo
Randomized crossover PK/PD work in younger and elderly healthy adults, published as Xia et al., Br J Clin Pharmacol 2026: hypnotic doses of fazamorexant induced less impairment of balance and cognition than zolpidem.
NCT06673927YZJ-1139-1-01Phase 1Completedn=104
A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of YZJ-1139 in Healthy Participants
metprimarySafety/tolerability and PK of single (2-80 mg) and multiple (10-60 mg x 7 days) doses; PD by Stanford Sleepiness Scale
Published as the first-in-human report (Ni et al., Drug Des Devel Ther 2025): rapid absorption (median Tmax 0.625-1.25 h), short half-life (1.91-3.68 h), minimal accumulation; all adverse events Grade 1 (drowsiness, lethargy, dizziness most frequent), no SAEs or deaths; dose-dependent hypnotic effect on the Stanford Sleepiness Scale.
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Fazamorexant oral tablet (evening dosing) Immediate-release tablets taken once daily in the evening. Phase 3 pivotal study YZJ-1139-3-01 tested 20 mg and 40 mg; the Phase 3 active-controlled study YZJ-1139-3-02 used 20 mg; Phase 2 tested 10/20/40/60 mg; first-in-human single doses 2-80 mg and multiple doses 10-60 mg for 7 days. The NMPA-approved label strength(s) are not confirmed in any open English-language source and are deliberately not asserted. | Oral | Once daily | — |
Mechanism of action
Dual orexin receptor antagonist (DORA): selectively blocks both orexin type 1 (OX1R/HCRTR1) and type 2 (OX2R/HCRTR2) receptors, with in vitro IC50 of 32 nM at OX1R and 41 nM at OX2R (vs 147 nM and 126 nM for suvorexant reported in the same paper). Orexin (hypocretin) signaling sustains wakefulness; antagonizing both receptors dampens wake-promoting arousal circuitry, enabling sleep onset and maintenance without GABAergic sedation. Fazamorexant was profiled for fast absorption (median Tmax 0.625-1.25 h) and a short half-life (1.91-3.68 h), aiming at rapid onset with minimal next-morning carryover; dose-dependent hypnotic effects were shown in the first-in-human study, and hypnotic doses impaired balance and cognition less than zolpidem in a randomized crossover study in younger and elderly adults.
| Target | Action | Affinity |
|---|---|---|
| OX2RprimaryHCRTR2 | Antagonist | IC50 41 nMⓘ |
| OX1RHCRTR1 | Antagonist | IC50 32 nMⓘ |
← Full YZJ-1139 compound page (identity, identifiers, all indications)
Sources
- Global Premiere of Phase III Clinical Results for Fazamorexant, a Class 1 Innovative Anti-Insomnia Drug by Yangtze River Pharmaceutical Group (World Sleep 2025, Singapore, 2025-09-05/10) — Yangtze River Pharmaceutical Group
- May 2026 China Innovative Drug Approvals — fazamorexant approved 2026-05-21 for adult insomnia (MAH: Jiangsu Haian Pharmaceutical / YRPG) — Dengyue Med (China regulatory news)
- NCT05525637 (YZJ-1139-3-01) — Phase 3, randomized, double-blind, placebo-controlled study of YZJ-1139 tablets in insomnia disorder (n=1,037) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT06671444 (YZJ-1139-1-12) — PK and safety of YZJ-1139 in severe renal impairment (n=16) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT06671470 (YZJ-1139-1-13) — Drug interaction study of YZJ-1139 tablets with ticagrelor (n=27) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT06671509 (YZJ-1139-1-11) — PK and safety of YZJ-1139 in mild/moderate hepatic impairment (n=24) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT06673927 (YZJ-1139-1-01) — First-in-human SAD/MAD study of YZJ-1139 in healthy participants (n=104) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT06680505 (YZJ-1139-2-01) — Phase 2 dose-ranging study of YZJ-1139 (10/20/40/60 mg) in primary chronic insomnia disorder (n=300) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT06680531 (YZJ-1139-1-14) — Drug interaction study of YZJ-1139 tablets with escitalopram oxalate (n=24) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT06685341 (YZJ-1139-1-02) — PK/PD study of YZJ-1139 with zolpidem and placebo comparators (n=20) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT06975514 (YZJ-1139-3-02) — Phase 3, randomized, double-blind, active-controlled (zolpidem 10 mg) PSG study of YZJ-1139 20 mg in insomnia disorder (n=61) — ClinicalTrials.gov (U.S. National Library of Medicine)
- Ni J, Jin L, Zhao D, et al. Pharmacokinetics, Pharmacodynamic, Safety and Tolerability of Fazamorexant, a Novel Dual Orexin Receptor Antagonist: Report of the First-in-Human Study. Drug Des Devel Ther. 2025;19:5271-5282 — Drug Design, Development and Therapy (Dove/Taylor & Francis) via PubMed Central
- Single-dose pharmacokinetics, tolerability, and physiologically based pharmacokinetic modeling of Fazamorexant in Chinese patients with hepatic impairment and in healthy controls. Front Pharmacol. 2026 — Frontiers in Pharmacology
- Xia et al. Hypnotic doses of fazamorexant induced less impairment on balance and cognition than zolpidem in healthy younger and elderly individuals. Br J Clin Pharmacol. 2026 — British Journal of Clinical Pharmacology (Wiley) / PubMed
- Yangtze River Pharmaceutical Group's Innovative Anti-insomnia Drug Fazamorexant Debut at the World Sleep Congress 2025 (2025-09-21, wire copy; confirms NDA submitted to CDE) — Yangtze River Pharmaceutical Group (via BioSpace)