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Abstract Background Prasinezumab, a monoclonal antibody that binds aggregated alpha-synuclein, is currently being investigated as a potential disease-modifying therapy in early-stage Parkinson’s disease (PD). In the PASADENA Phase II study, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). Here, we explore whether prasinezumab showed greater benefits on motor progression in rapidly compared with more slowly progressing subpopulations of PD. Methods Prasinezumab’s effects on disease progression were assessed in pre-specified rapidly progressing and more slowly progressing subpopulations of PD during the double-blind phase of PASADENA (e.g., participants taking MAO-B inhibitors at baseline vs. treatment-naïve participants). Results In the rapidly progressing subpopulations of PASADENA, participants treated with prasinezumab showed less decline in MDS-UPDRS Part III compared with more slowly progressing subpopulations of PD. Conclusion Efficacy of prasinezumab was greater in individuals with early-stage PD with a more rapidly progressing clinical phenotype.
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