HONOLULU — An investigational, intramuscular formulation of the dopamine agonist rotigotine is linked to significant improvement in symptoms and quality of life in patients with early Parkinson’s disease (PD), new research showed.

Rotigotine extended-release microspheres (LY03003; Luye Pharma) were designed to provide continuous dopaminergic stimulation via weekly injections.

In a large phase 3 trial, patients who received LY03003 for up to 24 weeks had greater improvement on the Unified Parkinson’s Disease Rating Scale (UPDRS) II and III and Clinical Global Impressions-Global Improvement (CGI-I) Scale than those in the placebo group and nearly 30% greater responder rates.

While most treatment-related adverse events (AEs) with LY03003 were deemed mild-to-moderate, serious AEs occurred in 4.8% vs 2.7% of the active and placebo groups, respectively.

Noting that the study showed “beautiful results” and a nice separation from placebo, principal investigator Piu Chan, MD, PhD, professor and director of the Clinical and Research Center for Parkinson’s Disease at Xuanwu Hospital of Capital Medical University, Beijing, China, said the drug was “very stable” and well tolerated by patients.

“All of this wasn’t a surprise, as rotigotine has been used for a long time, but for participants in this trial, they seemed to really like the delivery,” Chan told Medscape Medical News.

The findings were presented on October 7 at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2025.

Simplifies Delivery, Improves Adherence?

Rotigotine is a nonergoline dopamine receptor (D3/D2/D1) agonist. It received US approval in 2012 as a once-daily patch for the treatment of both PD and restless legs syndrome (RLS).

Interestingly, a very recent study showed a significant link between RLS and increased risk for PD.

In the new formulation, poly(lactide-co-glycolide) microspheres “were used to produce a gradual degradation process and sustained release” of rotigotine, the investigators noted. 

“Intramuscular injection also has the advantage of simplifying treatment regimen, improving compliance,” they added. LY03003 is approved for use in China.

Although it is not approved anywhere else at this time, an open-label pharmacokinetics study of the drug published in 2023 included data on patients treated in China, Japan, and the US.

In the current multicenter study, researchers enrolled 294 individuals from China aged 30 years or older and diagnosed with PD within the previous 5 years.

Half of the participants were randomly assigned to receive a weekly intramuscular injection of LY03003 for up to 24 weeks, and the other half received a matching placebo.

Those receiving the active treatment started at a dose of 14 mg that was then increased by an additional 14 mg increments up to a maximum of 56 mg per week. Patients were assessed at visits every 4 weeks, with the last assessment occurring at the start of week 29. 

The primary outcome was the change from baseline in UPDRS subtotal scores of parts II and III. Secondary outcomes included changes in CGI-I score and responder rates.

Significant Improvements

Results showed that the LY03003 group had greater improvement in subtotal scores on the UPDRS part II + III at the last assessment than the placebo group (-11.8 vs -5.6, respectively; P < .001), meeting its primary endpoint, as well as greater improvement on the CGI-I Scale (74.8% vs 54.2%; P < .001).

Additionally, those receiving active treatment showed greater responder rates, defined as a decline of at least 20% in the UPDRS part II + III score, than those receiving placebo (67.7% vs 38.5%, respectively; P < .001).

A greater percentage of the active treatment group also had a decline of at least 25% and at least 30% vs the placebo group (P < .001 for both comparisons).

The most common treatment-emergent AEs for the LY03003 group compared with the placebo group were injection site sclerosis (27.2% vs 12.3%), decreased prolactin (26.5% vs 2.7%), orthostatic hypotension (18.4% vs 21.2%), dizziness (12.2% vs 11%), urinary tract infection (10.9% vs 9.6%), and nausea (10.9% vs 5.5%).

“We have patients now who have been using this [drug] for more than a year and a half. It is safe, and it is effective,” Chan said.

He added that although no additional studies with LY03003 are in the works at this time, he is evaluating options for moving forward — including more research that could hopefully lead to approvals in other countries. 

A Better Option?

Commenting for Medscape Medical News, David Shprecher, DO, a movement disorder neurologist with Banner Sun Health Research Institute in Sun City, Arizona, noted that the study drug’s delivery system “addresses a key problem” with the version of rotigotine that is currently available in the US.

“Many patients, despite our best efforts at having them rotate sites, still have problems with excessive skin irritation from the adhesive patches that are used for the transdermal delivery system,” said Shprecher, who was not involved with the research.

“This novel delivery mechanism, with its intramuscular injection, would get around that problem,” he added.

Asked about the possibility of future FDA approval, Shprecher noted that, as was seen with the extended-release version of amantadine, the approval process can sometimes be expedited “when we already know the general side effect profile and efficacy of a particular drug, and if we can see that there’s a comparable pharmacokinetic profile” with its new formulation.

“So even though there are differences in the regulatory process and potentially in how trials are administered in China than in the United States, one could be cautiously optimistic this type of system could happen in an expedited review process and address unmet need in the US,” he said.

The study was funded by Luye Pharma and Merck. Chan reported having received speaker fees from Luye Pharma. Shprecher reported having no relevant financial relationships.