Presenter of 2 Presentations
DELAYED START ANALYSIS OF ROCHE PD MOBILE APPLICATION V2 IN PASADENA SHOWS PERSISTENT POSITIVE EFFECTS OF PRASINEZUMAB ON BRADYKINESIA PROGRESSION
Abstract
Aims
To determine whether the positive effects of prasinezumab on motor progression measured by the exploratory Roche PD Mobile Application v2 (PASADENA study Part 1; 0-52 weeks; NCT03100149) persisted in PASADENA Part 2 (52-104 weeks) when all patients received prasinezumab.
Methods
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 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
In Part 2, patients performed all assigned active tests on average 5/7 days per week, and collected an average of 7.3h smartwatch and 4h smartphone passive monitoring data daily. 6/17 sensor features showed persistent effects favoring prasinezumab (Figure 1). Three sensor features demonstrated persistent positive effects of prasinezumab surviving 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) (Figure 2).
Conclusions
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.
A 104-WEEK DELAYED-START ANALYSIS OF PASADENA (PHASE II STUDY EVALUATING THE SAFETY AND EFFICACY OF PRASINEZUMAB IN EARLY PARKINSON'S DISEASE)
Abstract
Aims
To describe the effect of prasinezumab on motor progression in early Parkinson’s disease (ePD) using a delayed-start analysis of Part 2 (Week 104) of the Phase II PASADENA study (NCT03100149). PASADENA Part 1 did not meet the primary endpoint (Movement Disorders Society–Unified Parkinson’s disease Rating Scale [MDS-UPDRS] sum of Parts I+II+III); however, prasinezumab-treated patients showed less motor progression compared with placebo.
Methods
Individuals with ePD (diagnosis ≤2 years at screening; Hoehn & Yahr Stages I–II) were randomised to receive intravenous prasinezumab every 4 weeks (low or high dose) for 104 weeks (early-start group), or placebo for 52 weeks followed by prasinezumab (low or high dose) for 52 weeks (delayed-start group).
Results
Worsening from baseline in MDS-UPDRS Part III scores was less in the early-start group (n=204) versus the delayed-start group (n=105) at Week 52 (5.02 [SE: 0.673] points vs. 6.25 [0.911] points, respectively) and at Week 104 (9.18 [0.994] vs. 11.12 [1.376] points, respectively) (Figure 1), with the largest group difference in the bradykinesia subscore (Figure 2). Fewer patients in the early-start group (79.1%) reached a ≥5-point increase in MDS-UPDRS Part III versus the delayed-start group (89.5%) (hazard ratio: 0.77 [80% CI 0.66–0.91]) (Figure 3). Digital motor scores were consistent with these results.
Conclusions
After 2 years, prasinezumab-treated individuals showed less motor progression on MDS-UPDRS Part III in the early-start versus the delayed-start group. The ongoing Phase IIb PADOVA (NCT04777331) study will further assess efficacy and safety of prasinezumab in people with ePD on stable symptomatic treatment.