rotigotine XR microspheres (LY03003) / Luye Group - LARVOL DELTA

Efficacy and safety of Rotigotine Extended-Release Microspheres in Early Parkinson's Disease (MDS Congress 2025) - "Objective: To assess the efficacy and safety of Rotigotine extended-release microspheres (LY03003) in patients with early Parkinson's disease Background: Treatment that provides a continuous flow of dopamine and thus can mimic normal physiological dopamine stimulation to improve motor control for patients... The results have demonstrated intramuscular injection of Rotigotine extended-release microspheres weekly can provide lasting improvement in symptoms and quality of life of PD patients with good safety and tolerance. Change in UPDRS Subtotal Scores of Part II and III Change in UPDRS Scores Part III"

Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease

Pharmacodynamics, safety pharmacology and local tolerance of rotigotine behenate extended-release microspheres. (PubMed, Toxicol Appl Pharmacol) - "In summary, RBEM's pharmacological activity is mediated by rotigotine release, with a favorable preclinical safety profile supporting clinical development. Respiratory, cardiovascular, and injection-site reactions should be prioritized in clinical monitoring."

Journal • PK/PD data • Cardiovascular • CNS Disorders • Hematological Disorders • Movement Disorders • Parkinson's Disease

20-Week Toxicity Study of Rotigotine Behenate Extended-Release Microspheres for Intramuscular Injection in Sprague Dawley Rats. (PubMed, Food Chem Toxicol) - "In conclusion, RBEM exhibited a good safety margin and can be used in phase I clinical trials. Keywords: Parkinson's disease; RBEM; Continuous dopaminergic stimulation; Repeated dose toxicity."

Journal • Preclinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease

20-Week Intramuscular Toxicity Study of Rotigotine Behenate Extended-Release Microspheres for Injection via Intramuscular Injection in Cynomolgus Monkeys. (PubMed, Food Chem Toxicol) - "The exposure generally increased in a dose-proportional manner. In summary, major toxicological effects are associated with the dopamine agonist-related properties of rotigotine, and the removal of foreign bodies caused by p oly(lactide-co-glycolide) (PLGA)and sodium carboxymethyl cellulose (SCMC), and the no-observed-adverse-effect-level (NOAEL) was 360 mg/kg."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Population pharmacokinetics of rotigotine extended-release microspheres for intramuscular injection in patients with early-stage Parkinson's disease. (PubMed, Br J Clin Pharmacol) - "Exposure differences were mainly attributed to body weight, while dose adjustments were not needed for patients of different racial identities."

Journal • PK/PD data • CNS Disorders • Movement Disorders • Parkinson's Disease

A study of the Genotoxicity, Fertility and Early Embryonic Development Toxicity of Rotigotine Behenate Extended-Release Microspheres. (PubMed, Basic Clin Pharmacol Toxicol) - "When female rats were administered with RBEM in the dose range 60 to 540 mg/kg given (i.m.), there were clear effects on fertility and early embryonic development. These results indicated that RBEM could induce toxicity in female rats and exert effect on fertility and early embryonic development stage."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

China’s NMPA accepts Luye’s NDA for long-acting rotigotine to treat Parkinson's disease (Bioworld) - "China’s National Medical Products Administration (NMPA) accepted Luye Pharma Group Ltd.’s NDA for rotigotine (LY-03003) extended-release microspheres and granted it priority review for treating Parkinson’s disease....If approved, LY-03003 would be the first long-acting extended-release microsphere formulation for the treatment of Parkinson’s disease (PD)."

Non-US regulatory • CNS Disorders • Parkinson's Disease

A Study to Evaluate the Pharmacokinetics and Safety of LY03003 in Patients With Advanced-stage PD (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Luye Pharma Group Ltd. | Recruiting ➔ Completed

Metastases • Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease

A Study to Evaluate the Effectiveness and Safety of LY03003 in Patients With Early Primary PD (clinicaltrials.gov) - P3 | N=294 | Completed | Sponsor: Luye Pharma Group Ltd. | Recruiting ➔ Completed | Trial completion date: May 2022 ➔ Sep 2022

Trial completion • Trial completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Studying spatial drug distribution in golf ball-shaped microspheres to understand drug release. (PubMed, J Control Release) - "Finally, two linear Level A in vitro-in vivo correlations were established and validated, indicating that the in vitro release testing could be a meaningful predictor for the in vivo performance of GSRM. Our work demonstrates the importance of studying drug distribution in complex microspheres to understand drug release."

Journal

Luye Pharma (02186): Phase III clinical trial of LY03003 in the treatment of Parkinson's disease reached the preset endpoint [Google translation] (Sina Corp) - P3 | N=294 | NCT04571164 | Sponsor: Luye Pharma Group Ltd. | "Luye Pharma...announced that the China Phase III clinical trial of the group's new drug under development, rotigotine sustained-release microspheres for injection (LY03003) in the treatment of Parkinson's disease, has reached the preset endpoint....The test results showed that, compared with the placebo group, the Unified Parkinson's Disease Rating Scale (UPDRS) II+III score in the LY03003 group was significantly improved compared with the baseline, and the difference between the two groups was statistically significant (P<0.001). Relevant secondary evaluation indicators were also statistically significant in both groups (P<0.001). In terms of safety, LY03003 was generally safe and well tolerated, and no serious adverse events related to the investigational drug occurred..."

P3 data • CNS Disorders • Parkinson's Disease

Continuous Activation of Dopamine Receptors Alleviates LPS-Induced Liver Injury in Mice via β-arrestin2 Dependent Akt/NF-κB Pathway. (PubMed, Front Pharmacol) - "In conclusion, activation of DRs inhibited the releases of pro-inflammatory cytokines and alleviated the immune-mediated liver injury induced by LPS in mice. The anti-inflammatory mechanism of RoMS may be related to the regulation of the β-arrestin2-dependent Akt/NF-κB signaling pathway."

IO biomarker • Journal • Preclinical • Hepatology • Immunology • Inflammation • Liver Failure • Oncology • ARRB1 • DRD2 • IL6 • TLR4 • TNFA

Dopamine receptor agonist rotigotine-loaded microspheres ameliorates sexual function deteriorated by fluoxetine in depression rats. (PubMed, ASN Neuro) - "These findings indicated that RoMS improved the fluoxetine-induced impairment of sexual function and did not affect its antidepressant efficacy in depressive rats, which provides a potential treatment for patients with depression that can reduce the possibility of sexual dysfunction. Additionally, co-administration of fluoxetine with RoMS may be beneficial for Parkinson's disease patients with depression."

Journal • Preclinical • CNS Disorders • Depression • Mood Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • Sexual Disorders

Rotigotine-loaded microspheres exerts the antinociceptive effect via central dopaminergic system. (PubMed, Eur J Pharmacol) - "Intracerebroventricular injection of domperidone abated the antinociceptive effect of RoMS...Intracerebroventricular injection of naloxone also alleviated the antinociceptive effect of RoMS. The results suggest that RoMS-mediated antinociceptive efficacy is associated with activating central dopamine D and D receptors. Opioid receptors play a role in the antinociceptive effect of RoMS."

Journal • CNS Disorders • Movement Disorders • Pain • Parkinson's Disease

Lipopolysaccharide/D-galactosamine-induced acute liver injury could be attenuated by dopamine receptor agonist rotigotine via regulating NF-κB signaling pathway. (PubMed, Int Immunopharmacol) - "In line with the above findings, the protective effects of rotigotine and RoMS were abrogated by haloperidol, a DA receptor antagonist. In conclusion, dopamine receptor agonist can regulate NF-κB inflammatory signaling pathway and exert protective effects in LPS/D-Gal-induced liver injury."

Journal • CNS Disorders • Hepatology • Immunology • Inflammation • Liver Failure • Movement Disorders • Parkinson's Disease • DRD2 • TNFA

A Study to Assess Pharmacokinetic Profiles of LY03003 and Neupro (clinicaltrials.gov) - P1; N=40; Completed; Sponsor: Luye Pharma Group Ltd.; Recruiting ➔ Completed

Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease

Luye Pharma (02186.HK): Rotigotine sustained-release microspheres for injection (LY03003) completed phase I clinical trials in Japan [Google translation] (Eastmoney.com) - P1, N=32; NCT04629404; Sponsor: Luye Pharma Group Ltd.; "Luye Pharma...announced that rotigotine sustained-release microspheres for injection (LY03003) have completed phase I clinical trials in Japan...A total of 35 Japanese Parkinson's disease (PD) patients were included in the study...The results show that LY03003 exhibits linear pharmacokinetic characteristics within the test dose range..."

P1 data • Trial completion • CNS Disorders • Parkinson's Disease

The Effect of Rotigotine Extended-Release Microspheres Alone or With Celecoxib on the Inflammatory Pain. (PubMed, Front Pharmacol) - "Clinical trials of rotigotine extended-release microspheres (RTGT-MS), which provides a sustained release of rotigotine for near 2 weeks in vivo, have been conducted in the treatment of Parkinson's disease (PD)...Chlorpromazine, a dopamine receptor blocker, not only weakened the analgesic effect of RTGT-MS, but also increased the levels of cAMP, PKA, COX-2, and PGE2. These findings provide a rationale for the combination of RTGT-MS and celecoxib in the treatment of PD, which may reduce the dose of celecoxib, thereby lowering the incidence of adverse effects and improving the pain management in PD patients."

Journal • CNS Disorders • Movement Disorders • Pain • Parkinson's Disease

A Clinical Trial to Evaluate the Pharmacodynamics/Pharmacokinetics and Safety of LY03003 in Early PD Patients (clinicaltrials.gov) - P1; N=32; Completed; Sponsor: Luye Pharma Group Ltd.

Clinical • New P1 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

A Study to Evaluate the Pharmacokinetics and Safety of LY03003 in Patients With Advanced-stage PD (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Luye Pharma Group Ltd.

Clinical • New P1 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

A Study to Evaluate the Human Tolerance and Pharmacokinetics of LY03003 (clinicaltrials.gov) - P1; N=20; Completed; Sponsor: Luye Pharma Group Ltd.

Clinical • New P1 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Antinociceptive effects of rotigotine-loaded microspheres and its synergistic interactions with analgesics in inflammatory pain in rats. (PubMed, Eur J Pharmacol) - "These findings suggest that RoMS can relieve inflammatory pain in rats. Furthermore, the combination of RoMS with acetaminophen or tramadol produces synergistic antinociception, which may be clinically worthy because combination therapies may reduce the drug doses required for antinociception."

Journal • CNS Disorders • Movement Disorders • Pain • Parkinson's Disease

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 (clinicaltrials.gov) - P1; N=56; Completed; Sponsor: Luye Pharma Group Ltd.; Recruiting ➔ Completed

Clinical • Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease

A Study to Evaluate the Effectiveness and Safety of LY03003 in Patients With Early Primary PD (clinicaltrials.gov) - P3; N=294; Recruiting; Sponsor: Luye Pharma Group Ltd.

Clinical • New P3 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Efficacy and Safety of Rotigotine in the Treatment of Patients With Early Stage of Primary Parkinson's Disease (clinicaltrials.gov) - P3; N=294; Completed; Sponsor: Peking University Third Hospital

Clinical • New P3 trial • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease