Objective: To evaluate the effect of prasinezumab on slowing down disease progression in participants with early-stage Parkinson’s disease (PD) on stable symptomatic medication.

Background: Prasinezumab was shown to potentially delay motor progression in patients with early-stage PD who were either treatment-naïve or on monoamine oxidase type B inhibitor (MAO-Bi) therapy in the PASADENA study.

Method: The PADOVA study (NCT04777331) evaluated the efficacy, safety and pharmacokinetics of prasinezumab in participants with early-stage PD on stable MAO-Bi or levodopa monotherapy for ≥3 months prior to randomization. The primary endpoint was time to confirmed motor progression, defined as ≥5-points increase from baseline on MDS-UPDRS Part III in OFF-medication state. The primary analysis was a treatment comparison between prasinezumab and placebo using a stratified log-rank test at a two-sided 5% significance level. Secondary and exploratory efficacy assessments included continuous and time-to-event measures of disease progression, and participant- and clinician-rated global measures of change.

Results: A total of 586 participants were enrolled; 74.2% were receiving levodopa and 25.8% MAO-Bi. While the primary endpoint did not reach statistical significance (p=0.0657), prasinezumab indicated a trend for potential clinical efficacy with an HR (95% CI)=0.84 (0.69–1.01). A more pronounced effect was seen in the levodopa population (HR=0.79 [0.63–0.99]). Pre-specified supplementary covariate-adjusted analyses showed a nominally significant effect on the primary endpoint (HR=0.81 [0.67–0.98]); and in the levodopa population (HR=0.76 [0.61–0.95]). Consistent positive trends across secondary and exploratory endpoints were also observed. Prasinezumab-treated participants showed numerically less decline in neuromelanin MRI intensity and volume of substantia nigra pars compacta and statistically significantly less accumulation of iron in an exploratory biomarker analysis. Prasinezumab was well tolerated with no new safety signals observed.

Conclusion: Even though the primary endpoint of PADOVA was missed, results suggest a possible clinical benefit of prasinezumab in slowing down disease progression in early-stage PD on top of efficacious symptomatic medication. These results warrant further exploration and will inform future clinical trials.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/padova-topline-results-from-a-phase-iib-study-of-prasinezumab-in-early-stage-parkinsons-disease-participants-on-stable-symptomatic-treatment/