Objective: To determine whether the positive effects of prasinezumab on motor progression measured by Roche PD Mobile Application (PASADENA study Part 1; 0-52 weeks; NCT03100149) persisted in PASADENA Part 2 (52-104 weeks) during which all patients received prasinezumab.

Background: Prasinezumab was designed to target aggregated alpha-synuclein and slow disease progression in PD. The efficacy of prasinezumab was tested in PASADENA study Part 1 in 316 individuals with early-stage PD. While the primary study outcome was not met (MDS-UPDRS total score), reduced clinical decline of motor signs was detected by the MDS UPDRS part III and the newly developed Roche PD Mobile Application. All Part 1 patients received prasinezumab in PASADENA Part 2 (weeks 52-104), enabling an exploratory delayed-start analysis to determine the persistence of effects in Part 2.

Method: 316 individuals with early PD were randomized to prasinezumab (low or high dose) for 104 weeks (early-start group), or placebo for 52 weeks then prasinezumab (low or high dose) for 52 weeks (delayed-start group). Roche PD Mobile Application v2 administered daily “active tests” and “passively monitored” motor behavior in daily life (phone, smartwatch). Seventeen pre-specified sensor features were aggregated over every two-week period until the start of dopaminergic therapy. Linear mixed effect models or mixed models for repeated measures were fitted to each feature’s change from baseline to week 104. Exploratory significance was defined as α<0.2 and false discovery rate (FDR) correction applied at 15%.

Results: Individuals with PD performed all assigned active tests on average 5/7 days per week in part 2, and collected an average of 7.3h smartwatch and 4h smartphone passive monitoring data daily. 6/17 sensor features showed persistent effects favoring the early-start group, three of which survived FDR correction: speeded tapping variability (β=-0.0017, p=0.03), U-turn test (β =0.0006, p = 0.02), and daily gesture power (Week 104 mean difference= 0.21, p=0.02).

Conclusion: The early-start prasinezumab group showed a persistent reduction in bradykinesia progression compared with the delayed-start group as measured by the Roche PD Mobile Application v2.
This material was presented at ADPD, March 19, 2022.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/exploratory-analysis-of-the-effect-of-delayed-start-prasinezumab-on-motor-sign-progression-measured-with-the-roche-pd-mobile-application-v2-pasadena-phase-ii-parts-1-and-2/