Prasinezumab (DB14788): An Investigational Anti-Alpha-Synuclein Antibody for Parkinson's Disease

1. Executive Summary

Prasinezumab (DB14788) is an investigational humanized monoclonal antibody targeting aggregated alpha-synuclein (α-syn), a protein central to the pathology of Parkinson's disease (PD). Developed collaboratively by Prothena and Roche, Prasinezumab aims to slow disease progression by inhibiting the accumulation and spread of pathogenic α-synuclein aggregates. Clinical development has progressed through Phase 2b, evaluating the therapy primarily in early-stage PD populations.

Key findings indicate that Prasinezumab possesses a generally favorable safety and tolerability profile, demonstrated across multiple clinical trials, including long-term open-label extensions involving over 900 participants. Immunogenicity concerns have not been significant. However, efficacy results have been mixed. While Phase 1 studies showed peripheral target engagement, the pivotal Phase 2 PASADENA (Part 1) and Phase 2b PADOVA trials failed to meet their primary endpoints assessing overall clinical progression or time to motor progression, respectively, in the intent-to-treat populations over 52-104 weeks. Despite these outcomes, consistent signals suggesting a slowing of motor decline, specifically measured by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, were observed in both trials, particularly in pre-specified subgroup analyses (e.g., patients on levodopa in PADOVA) and in long-term (4-year) open-label extension data compared to external controls.