Small Molecule · LY03003

Rotigotine extended-release microspheres (LY03003)

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

Once-weekly intramuscular extended-release microsphere depot of rotigotine, a non-ergoline dopamine agonist, developed by Luye Pharma and approved in China (brand Jinyouping / 金悠平, NMPA, June 2024) for Parkinson's disease — the first long-acting extended-release microsphere formulation for PD. Rotigotine itself is an established molecule marketed since 2007 as the once-daily Neupro transdermal patch (UCB); LY03003 is Luye's novel depot presentation, designed to hold rotigotine plasma concentrations stable across seven days per injection and thereby deliver continuous dopaminergic stimulation (CDS), reducing the pulsatile receptor stimulation implicated in motor complications and the on-off phenomenon. Pharmacologically rotigotine is a full agonist across dopamine receptors with highest affinity for D3 (Ki 0.71 nM) over D2 (13.5 nM) and D1 (83 nM), with additional agonism at 5-HT1A (Ki 30 nM) and antagonism at alpha-2B adrenoceptors (Ki 27 nM). The Chinese Phase 3 (NCT04571164, n=294) met its primary endpoint (UPDRS Part II+III vs placebo, p<0.001); full results were presented at MDS 2025. A separate Luye program, LY03009 (rotigotine behenate microspheres), is a once-monthly prodrug follow-on and is not this compound.

Also known as: LY03003, LY-03003, Jinyouping, 金悠平, rotigotine, Rotigotine extended-release microspheres for injection, Rotigotine microspheres for injection, 99755-59-6

Data current as of

Key facts

Modality
Small molecule
Chemical class
aminotetralin, thiophene
Chemistry
Single enantiomer
Mechanism
D3 agonist
Highest phase
Approved
Lead indication
Parkinson's disease
Developer
Luye Pharma Group Ltd. (2186.HK)
Designations
NMPA Priority Review (China; NDA Accepted 2023-08-01)
Trials
7 tracked · 12 sites

Mechanism of action#

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.

0.1 nM1 nM10 nM100 nMD3D3 — agonist — Ki 0.71 nMKi 0.71 nMD2D2 — agonist — Ki 13.5 nMKi 13.5 nM5-HT1A5-HT1A — agonist — Ki 30 nMKi 30 nM
Binding affinity on a log scale — further left is more potent. Values from the sourced literature (see table).
TargetActionAffinity
D3primaryDRD3AgonistKi 0.71 nMⓘ
5-HT1AHTR1AAgonistKi 30 nMⓘ
D2DRD2AgonistKi 13.5 nMⓘ

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—

Development timeline#

2014201620182020202220242026TodayPhase 115 Mar 2013 — phase change — 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.Phase 319 Jul 2022 — readout (met) — 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.11 May 2020 — phase change — 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.Filed (NDA)1 Aug 2023 — phase change — 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 3.1 Aug 2023 — NDA/BLA filed — China NDA for LY03003 accepted by CDE with priority review designationApproved7 Oct 2025 — Conference presentation — Full Phase 3 results for rotigotine extended-release microspheres in early Parkinson's disease presented at MDS 202520 Jun 2024 — phase change — 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.20 Jun 2024 — NMPA approval (China) — NMPA approves Jinyouping (rotigotine microspheres for injection, LY03003) for Parkinson's disease in China
Phase change Readout Event UpcomingHover a marker for details.
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.

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

ApprovedApprovedParkinson's disease indication →

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.

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#

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

Show all 7 trials

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

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)
Show all 12 sources
  1. NCT04630860 — PK and Safety of LY03003 in Patients With Advanced-stage PD (Phase 1) — ClinicalTrials.gov (U.S. National Library of Medicine)
  2. 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