Daniel Umbricht, Switzerland
F. Hoffmann - La Roche Ltd Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Discovery and Translational AreaAuthor Of 1 Presentation
A PHASE 2 STUDY TO EVALUATE THE SAFETY AND EFFICACY OF PRASINEZUMAB IN EARLY PARKINSON'S DISEASE (PASADENA): RESULTS FROM PART 1 WEEK–52
Abstract
Aims
This study aimed to evaluate the efficacy and safety of prasinezumab, a monoclonal antibody which targets extracellular α-synuclein, following 52 weeks of treatment in early PD.
Methods
A 52-week randomised, double-blind, placebo-controlled study (PASADENA Part 1) was performed to assess efficacy and safety of prasinezumab (low or high dose) in early PD (N=316, diagnosis ≤2 years; Hoehn & Yahr Stages I–II). The primary endpoint was the change in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total score (Parts I + II + III) from baseline to Week 52. Secondary and exploratory endpoints included: changes in MDS-UPDRS Part III, MDS-UPDRS Part III subscores, other clinical and digital endpoints and imaging biomarkers.
Results
At Week 52, MDS-UPDRS Total score was –1.30 (–14%; 80% CI: –3.18, 0.58) for pooled doses versus placebo; –2.02 for low dose (–21.5%; 80% CI: –4.21, 0.18) and –0.62 for high dose (–6.6%; 80% CI: –2.82, 1.58). MDS-UPDRS Part III was –1.88 (–35.0%; 80% CI: –3.31, –0.45) for pooled treatment groups versus placebo; –2.44 for low dose (–45.4%; 80% CI: –4.09, –0.78) and –1.33 for high dose (–24.7%; 80% CI: –2.99, 0.34). MDS-UPDRS Part III site rating, MDS-UPDRS Part III bradykinesia subscore, digital motor endpoints, and time to worsening of motor symptoms supported the MDS-UPDRS Part III positive motor signals. There were no life-threatening adverse events or immunogenicity concerns.
Conclusions
Prasinezumab had a favourable safety profile and is the first potentially disease-modifying, anti-α-synuclein antibody to show efficacy signals on clinical progression of core motor features of PD. Further studies are warranted.