Objective: Evaluate the long-term effectiveness of potential disease-modifying treatments (DMTs) in Parkinson’s disease (PD) using a modelling-based virtual comparator and explore patient-relevant benefits through the concept of ‘time saved’.

Background: Current measures are unable to detect early changes in ability of individuals with PD to perform daily activities and there are currently no suitable functional endpoints for registrational trials of investigational treatments with disease modifying potential.

Method: Models describing clinician-assessed MDS-UPDRS Part III OFF medication state and patient-reported Part II progression were developed from Parkinson’s Progression Markers Initiative (PPMI) observational data and could successfully reproduce progression in the placebo arm of the PASADENA trial (NCT03100149). Long-term treatment effects were evaluated by comparing 5-year data from the prasinezumab Open-Label Extension (OLE) with simulated trajectories based on PPMI data. Exploratory analyses of participant withdrawal in PPMI were conducted to better characterize the limitations of the virtual comparator.

Results: A treatment-related slowing of disease progression was evident earlier when measured by MDS-UPDRS Part III off medication score than by Part II. This temporal sequence aligns with theoretical expectations and modelling results that suggest changes in motor impairment typically precede functional decline by several years. The observed PASADENA OLE outcomes consistently deviated from the model-predicted progression, suggesting a sustained treatment effect. On average, participants were approximately 2 years less advanced in disease severity 5 years after the start of the trial compared to the virtual comparator. Withdrawal increased markedly around year 5 in the PPMI cohort.

Conclusion: The comparison of PASADENA OLE data with PPMI-based model predictions supports potential delay of motor symptoms with an estimated 2 years of ‘time saved’ providing an intuitive measure of long-term benefit for individuals living with PD. It can be hypothesized that among the increased number of participants withdrawing in year 5 in the PPMI cohort, participants progressing more rapidly might have been overrepresented. This emphasizes the critical need to account for missing data when assessing long-term, model-based treatment effects.

Abstract was previously presented at ADPD 2026 on 19 March 2026.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/modeling-parkinsons-disease-progression-to-quantify-long-term-treatment-effects-via-the-concept-of-time-saved/