Sustained effect of prasinezumab on Parkinson's disease motor progression in the open-label extension of the PASADENA trial

Nat Med. 2024 Dec;30(12):3669-3675. doi: 10.1038/s41591-024-03270-6. Epub 2024 Oct 8.

Abstract

The Phase II trial of Anti-alpha-Synuclein Antibody in Early Parkinson's Disease (PASADENA) is an ongoing double-blind, placebo-controlled trial evaluating the safety and efficacy of prasinezumab in early-stage Parkinson's disease (PD). During the double-blind period, prasinezumab-treated individuals showed less progression of motor signs (Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III) than placebo-treated individuals. We evaluated whether the effect of prasinezumab on motor progression, assessed as a change in MDS-UPDRS Part III score in the OFF and ON states, and MDS-UPDRS Part II score, was sustained for 4 years from the start of the trial. We compared participants enrolled in the PASADENA open-label extension study with those enrolled in an external comparator arm derived from the Parkinson's Progression Markers Initiative observational study. The PASADENA delayed-start (n = 94) and early-start (n = 177) groups showed a slower decline (a smaller increase in score) in MDS-UPDRS Part III scores in the OFF state (delayed start, -51%; early start, -65%), ON state (delayed start, -94%; early start, -118%) and MDS-UPDRS Part II (delayed start, -48%; early start, -40%) than did the Parkinson's Progression Markers Initiative external comparator (n = 303). This exploratory analysis, which requires confirmation in future studies, suggested that the effect of prasinezumab in slowing motor progression in PD may be sustained long term. PASADENA ClinicalTrials.gov no. NCT03100149 .

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Disease Progression*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / physiopathology
  • Treatment Outcome
  • alpha-Synuclein

Substances

  • Antibodies, Monoclonal, Humanized
  • alpha-Synuclein

Associated data

  • ClinicalTrials.gov/NCT03100149