At the AD/PD 2026 International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders, Roche showcased new five-year data from the Phase II PASADENA trial (NCT03100149). While the study failed to reach its primary endpoint in the randomised 52-week study, analysis of the five-year data from the open-label extension and mathematical modelling suggests that prasinezumab could have potential sustained clinically meaningful effects on motor and function progression in patients with early Parkinson’s disease (PD).
At AD/PD 2026, Roche announced that patients treated with prasinezumab for five years demonstrated a sustained slowing of motor and functional decline compared to an external comparator group, taken from the Parkinson’s Progression Markers Initiative (PPMI) sporadic PD cohort. The use of symptomatic therapies was generally higher in the PPMI cohort in comparison to the treatment arm, with the average levodopa equivalent daily dose approximately 100mg higher in the external comparator group through Year 5. The relative differences in Movement Disorder Society-Sponsored Unified Parkinson’s Disease Rating Scale Revision (MDS-UPDRS) Part III scores between patients treated with 1,500mg of prasinezumab and the external comparator group at Year 5 are a 41% decline in off-medication score and a 95% decline in on-medication score. This supports the potential disease-modifying properties of prasinezumab, with sustained results on slowing motor progression and function decline in PD.
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During the AD/PD 2026 “AI and digital tools for AD/PD care” presentation, Roche also introduced a new concept of shifting the efficacy paradigm for measuring disease progression in PD from the traditional measure using point change in MDS-UPDRS to a new approach of “time gained” or “years of progression avoided” metric. The “time gained” approach could address the challenges associated with assessing disease-modifying properties of pipeline drugs. For example, in early-stage PD, the underlying disease progression is slow and highly variable, making it difficult to measure incremental changes in MDS-UPDRS points. In addition, symptomatic therapy can mask the treatment effects of investigative products for disease modification. These challenges may have contributed to PASADENA missing its primary endpoint. The “time gained” analysis could mitigate the need for clinical trials with long study durations and large sample sizes to achieve statistical separation and provide a patient-centric metric to detect disease-modifying properties.
Using the natural history data from PPMI and disease progression modelling, Roche constructed a virtual comparator and aligned it with the PASADENA five-year data. Results from the mathematical disease model demonstrated an average of two years of “time gained” across motor and functional domains in patients who received prasinezumab treatment for five years. Roche noted that the level of PD progression in patients treated with prasinezumab for five years was similar to the virtual comparator at Year 3 without prasinezumab treatment.
Roche continues to build a compelling case, reinforcing the potential disease-modifying properties of prasinezumab in patients with early Parkinson’s disease. However, since the five-year analyses lack a placebo arm and rely on an external cohort and a virtual comparator, a potential placebo effect cannot be ruled out. These positive exploratory findings must be replicated in a large Phase III clinical trial; the ongoing Phase III randomised, double-blind, placebo-controlled study of prasinezumab in patients with early PD has a primary completion date of June 2029 (PARAISO; NCT07174310). While the PASADENA trial relied on change from baseline in MDS-UPDRS total scores over time, the PARAISO study uses a time-to-event primary endpoint, which focuses on time to confirmed motor progression as assessed by MDS-UPDRS Part III to measure delay in disease progression. Roche is determined to bring prasinezumab to market and has refined its choice of endpoints to capture disease-modification properties in patients with early PD. The “time gained” analysis of the PASADENA study translates complex clinical data into a patient-centred measure and supports the rationale for the pivot to a time-to-event endpoint used in the PARAISO study.
