1. Cinpanemab did not show clinical efficacy in preventing early Parkinson’s disease (PD) progression compared to placebo.

2. There was no difference in imaging results of dopamine transporters between cinpanemab and placebo groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: PD is the second most prevalent neurodegenerative disease worldwide. The mainstay of treatment is dopamine replacement with levodopa, which is effective in managing PD symptoms. Current therapies, however, do not slow disease progression. Drug-resistant symptoms may also emerge over time. Therefore, disease-modifying PD drugs are the subject of active investigation. Cinpanemab is a human-derived monoclonal antibody targeting aggregated extracellular α-synuclein, a protein involved in disrupting dopamine signaling underlying the pathology of PD. The current study was a phase two randomized controlled trial assessing the efficacy of cinpanemab in participants with early PD. Participants were randomized to receive infusions of a placebo control or cinpanemab at a dose of 250mg, 1250mg, or 3500mg every 4 weeks. Compared to the placebo, cinpanemab recipients did not show significant improvements in PD clinical rating scores at 52 and 72 weeks. Imaging to examine dopamine signaling showed no differences between cinpanemab and placebo groups. The trial was halted at 72 weeks due to lack of efficacy. These results indicate that targeting extracellular α-synuclein may not be sufficient in modifying PD’s progression.

Click here to read the study in NEJM

In-Depth [randomized control trial]: The present study was a 52-week, double-blind, randomized controlled phase two trial investigating the efficacy of cinpanemab for treating early PD. Participants between 40 and 80 years of age were included if they had early-stage PD, scored no more than 2.5 on the modified Hoehn and Yahr scale of PD progression, had not received PD treatment, and had dopamine transporter single-photon-emission computed tomography (DaT-SPECT) indicated dopaminergic deficit consistent with PD. Overall, 357 participants were enrolled, randomized in a 2:1:2:2 ratio to receive intravenous infusions of placebo or cinpanemab every four weeks for 52 weeks. Afterward, placebo recipients started to receive cinpanemab at 250mg, 1250mg, or 3500mg dose until 112 weeks. The primary outcome was the change from baseline in the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS, high scores indicating more severe symptoms), at 52 and 72 weeks. At 72 weeks, the adjusted mean difference between participants who received cinpanemab for 72 weeks and the pooled group who started cinpanemab at 52 weeks was -0.9 (95% Confidence Interval [CI], -5.6 to 3.8), 0.6 (95% CI, -4.6 to 3.0), and -0.8 (95% CI, -4.6 to 3.0) for the 250mg, 1250mg, and 3500mg groups, respectively. Similar results were observed in the MDS-UPDRS subscales and quality of life measures. Overall, cinpanemab was not shown to be efficacious in clinical measures of early PD.

Image: PD

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