LY03003 · program

Rotigotine extended-release microspheres (LY03003) for Parkinson's disease

ApprovedApprovedLuye Pharma Group Ltd. (2186.HK)
  • NMPA Priority Review (China; NDA Accepted 2023-08-01)

Rotigotine extended-release microspheres for injection (LY03003; brand Jinyouping / 金悠平), Luye Pharma's once-weekly intramuscular dopamine-agonist depot, approved by China's NMPA in June 2024 for Parkinson's disease under priority review — the world's first long-acting extended-release microsphere formulation for PD and the first weekly dopamine agonist. The approval rests on a Chinese Phase 1 package plus the pivotal Phase 3 NCT04571164 (n=294 early-stage idiopathic PD, randomized 1:1 to weekly LY03003 or placebo), which met its primary endpoint of UPDRS Part II+III improvement vs placebo (p<0.001) with statistically significant secondary endpoints and no IMP-related SAEs (topline announced 2022-07-19; full results presented at MDS 2025). The CDS rationale: stable 7-day rotigotine exposure avoids pulsatile dopaminergic stimulation, aiming to reduce on-off fluctuations and delay motor complications. Global status beyond China is unclear from open sources: a US bridging-PK package was built through 2020 (including a Neupro-referenced crossover), Luye stated in January 2021 that the product was in Phase 3 in China and the US, and a Japanese Phase 1 completed in 2021 — but no US or Japanese Phase 3 registration or filing has appeared on ClinicalTrials.gov or in company releases since, so no ex-China phase is asserted. A once-monthly rotigotine behenate microsphere follow-on (LY03009) is a separate program.

Data current as of

Development timeline

ApprovedJun 2024 – Oct 2025
  1. Conference presentationFull Phase 3 results for rotigotine extended-release microspheres in early Parkinson's disease presented at MDS 2025↗
  2. NMPA approved Jinyouping (rotigotine microspheres for injection) for marketing in China for Parkinson's disease, announced by Luye 2024-06-20 (wire coverage dated the corporate announcement 2024-06-19; the exact NMPA certificate date is not public, so this date is an upper bound). First marketing authorization anywhere for the weekly depot.↗
  3. NMPA approval (China)NMPA approves Jinyouping (rotigotine microspheres for injection, LY03003) for Parkinson's disease in China↗
Filed (NDA)Aug 2023
  1. China's CDE accepted the NDA for rotigotine extended-release microspheres for injection (LY03003) and granted priority review designation, per Luye's 2023-08-01 announcement. Submission supported by several Phase 1 trials plus the single Phase 3.↗
  2. NDA/BLA filedChina NDA for LY03003 accepted by CDE with priority review designation↗
Phase 3May 2020 – Jul 2022
  1. metChinese pivotal Phase 3 of weekly LY03003 in early-stage Parkinson's disease (n=294) met its primary endpoint: statistically significant improvement in UPDRS Part II+III vs placebo (p<0.001), significant secondary endpoints, no IMP-related SAEs.↗
  2. Pivotal Chinese Phase 3 NCT04571164 started: multicenter, randomized, double-blind, placebo-controlled study of weekly IM LY03003 vs placebo in 294 patients with early primary Parkinson's disease; primary endpoint UPDRS Part II+III.
Phase 1Mar 2013
  1. First-in-human tolerance and PK study of LY03003 started (NCT04627155, n=20; registered retrospectively in 2020). A parallel early PK/safety study in early-stage PD patients (NCT02055274) started October 2013.

Readouts

  • 2022-07-19ReportedTopline datametNCT04571164

    Chinese pivotal Phase 3 of weekly LY03003 in early-stage Parkinson's disease (n=294) met its primary endpoint: statistically significant improvement in UPDRS Part II+III vs placebo (p<0.001), significant secondary endpoints, no IMP-related SAEs. ↗

Clinical trials in Parkinson's disease

NCT04630860Phase 1Completedn=30

A Study to Evaluate the Pharmacokinetics and Safety of LY03003 in Patients With Advanced-stage PD

Started Jul 2020· Primary completion May 2021· 📍 1 site across 1 country (China)

NCT04384666Phase 1Completedn=56

A Randomized, Open-Label, Crossover Study to Evaluate the Pharmacokinetic Profiles of Rotigotine After a Single Dose of LY03003 (28 mg) Versus After a Week of Daily NEUPRO Transdermal Patch (4 mg Every 24 Hours) in Healthy Volunteers

Started Jun 2020· Primary completion Aug 2020· 📍 1 site across 1 country (United States)

NCT04571164Phase 3Completedn=294

A Study to Evaluate the Effectiveness and Safety of LY03003 in Patients With Early Primary PD

Started May 2020· Primary completion Mar 2022· 📍 1 site across 1 country (China)

NCT03733561Phase 1Completedn=40

A Study to Assess Pharmacokinetic Profiles of LY03003 and Neupro

Started Nov 2018· Primary completion Dec 2018· 📍 1 site across 1 country (United States)

NCT04045678Phase 1Completedn=30

A Multiple Ascending Dose Study With LY03003 in Patients With Early-stage Parkinson's Disease

Started Oct 2017· Primary completion Apr 2019· 📍 3 sites across 1 country (China)

NCT02055274Phase 1Completedn=39

Pharmacokinetics and Safety Study of LY03003 in Patients With Early-stage Parkinson's Disease

Started Oct 2013· Primary completion Aug 2015· 📍 5 sites across 1 country (United States)

NCT04627155Phase 1Completedn=20

A Study to Evaluate the Human Tolerance and Pharmacokinetics of LY03003

Started Mar 2013· Primary completion May 2013

Formulations

FormulationRouteRegimenPharmacokinetics
Rotigotine extended-release microspheres for injection, once-weekly IM depot (Jinyouping)Extended-release microsphere depot
Once-weekly intramuscular injection. The Chinese Phase 3 (NCT04571164) used 56 mg weekly vs placebo for up to 24 weeks per MDS 2025 abstract coverage. The Japanese Phase 1 tested five consecutive weekly IM injections at 14, 28 or 56 mg with dose-proportional exposure; the US healthy-volunteer PK crossover (NCT04384666) compared a single 28 mg injection with a week of Neupro 4 mg/24 h patches.
Intramuscular depot (LAI)Once weekly—

Mechanism of action (compound-wide)

Rotigotine is a non-ergoline full agonist across dopamine receptors with a rank-order preference for D3: in standard radioligand binding it shows Ki 0.71 nM at D3, 3.9-15 nM across D4 variants, 5.4 nM at D5, 13.5 nM at D2 and 83 nM at D1, with functional agonist potency rank D3>D2L>D1=D5>D4.4 (2,600- and 53-fold more potent than dopamine at D3 and D2L respectively). Among non-dopaminergic sites it is a weak-but-significant agonist at 5-HT1A (Ki 30 nM) and an antagonist at alpha-2B adrenoceptors (Ki 27 nM). In Parkinson's disease the therapeutic action is attributed to activation of postsynaptic D2-family receptors in the striatum. The LY03003 program's differentiating hypothesis is pharmacokinetic, not pharmacodynamic: an extended-release microsphere depot injected intramuscularly once weekly holds rotigotine plasma concentrations stable over seven days, providing continuous dopaminergic stimulation (CDS) and avoiding the pulsatile stimulation associated with motor complications — the same CDS rationale as the Neupro patch, extended from 24 hours to a week per administration.

TargetActionAffinity
D3primaryDRD3AgonistKi 0.71 nMⓘ
5-HT1AHTR1AAgonistKi 30 nMⓘ
D2DRD2AgonistKi 13.5 nMⓘ

← Full LY03003 compound page (identity, identifiers, all indications)

Sources

  1. China's NMPA Accepts and Grants Priority Review Designation to the New Drug Application for Luye Pharma's Rotigotine Extended-Release Microspheres (2023-08-01) — Luye Pharma Group / Luye Life Sciences
  2. Efficacy and safety of Rotigotine Extended-Release Microspheres in Early Parkinson's Disease — MDS 2025 abstract — International Parkinson and Movement Disorder Society (MDS Abstracts)
  3. Luye Pharma's Innovative Formulation LY03003 Meets Primary Endpoints in Phase III Clinical Trial for Treating Parkinson's Disease (2022-07-19) — Luye Pharma Group
  4. Luye Pharma's Jinyouping (Rotigotine Microspheres for Injection) Approved for Marketing in China (2024-06-20) — Luye Pharma Group
  5. NCT02055274 — Pharmacokinetics and Safety Study of LY03003 in Patients With Early-stage Parkinson's Disease (Phase 1) — ClinicalTrials.gov (U.S. National Library of Medicine)
  6. NCT03733561 — A Study to Assess Pharmacokinetic Profiles of LY03003 and Neupro (Phase 1) — ClinicalTrials.gov (U.S. National Library of Medicine)
  7. NCT04045678 — A Multiple Ascending Dose Study With LY03003 in Patients With Early-stage Parkinson's Disease (Phase 1) — ClinicalTrials.gov (U.S. National Library of Medicine)
  8. NCT04384666 — PK crossover: single 28 mg LY03003 vs a week of daily NEUPRO 4 mg/24 h in healthy volunteers (Phase 1) — ClinicalTrials.gov (U.S. National Library of Medicine)
  9. NCT04571164 — A Study to Evaluate the Effectiveness and Safety of LY03003 in Patients With Early Primary PD (Phase 3, n=294, completed 2022-09-27) — ClinicalTrials.gov (U.S. National Library of Medicine)
  10. NCT04627155 — A Study to Evaluate the Human Tolerance and Pharmacokinetics of LY03003 (first-in-human, started 2013-03-15) — ClinicalTrials.gov (U.S. National Library of Medicine)
  11. NCT04630860 — PK and Safety of LY03003 in Patients With Advanced-stage PD (Phase 1) — ClinicalTrials.gov (U.S. National Library of Medicine)
  12. Scheller D, et al. The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson's disease. Naunyn Schmiedebergs Arch Pharmacol. 2009;379(1):73-86 — Naunyn-Schmiedeberg's Archives of Pharmacology / PubMed