An exploratory analysis of data from the PASADENA trial and the Parkinson’s Progression Markers Initiative (PPMI) suggests that prasinezumab, a monoclonal antibody targeting aggregated alpha-synuclein, may offer sustained benefits in slowing motor progression in individuals with early-stage Parkinson's disease (PD). The study, published in Nature Medicine, compared outcomes over four years in participants who received early-start prasinezumab versus a delayed-start group and a propensity score-weighted PPMI cohort.
The PASADENA trial was a randomized, double-blind, placebo-controlled study, followed by a 5-year open-label extension (OLE). Participants with early-stage PD (diagnosed ≤2 years, Hoehn and Yahr stages 1-2) received either intravenous prasinezumab (1,500 or 4,500 mg) or placebo for 52 weeks, followed by prasinezumab in the delayed-start group. The PPMI is an observational study designed to identify biomarkers of PD progression.
The primary endpoint of the analysis was the change from baseline to year 4 in motor progression, as measured by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III. Secondary endpoints included changes in levodopa equivalent daily dose (LEDD) and severity of motor complications.
Impact on Motor Progression
Results indicated that the early-start prasinezumab group experienced a slower rate of motor progression compared to the PPMI cohort. This finding was supported by both propensity score analysis and disease modeling, which accounted for differences in baseline characteristics and LEDD usage between the groups. Specifically, the propensity score-weighted analysis demonstrated a statistically significant difference in MDS-UPDRS scores between the early-start group and the PPMI cohort.
Disease Modeling Reinforces Findings
Disease modeling, a quantitative approach to predict disease progression, further supported these findings. By simulating PD progression based on PPMI data and comparing it to the PASADENA data, researchers observed that the early-start prasinezumab group performed better than predicted by the model, suggesting a potential disease-modifying effect.
Considerations and Future Directions
The study authors noted several limitations, including the observational nature of the PPMI cohort and the potential for unmeasured confounders. However, they emphasized the consistency of the findings across different analytical approaches. "These results support the potential of prasinezumab to modify disease progression in early Parkinson's disease," the authors stated. Further research, including larger, controlled trials, is needed to confirm these findings and fully elucidate the long-term effects of prasinezumab on PD progression.
The trial was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines, with all participants providing written informed consent.
