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

Abstract The PASADENA study is an ongoing Phase II, multicenter, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of intravenous prasinezumab, administered every 4 weeks, in early-stage Parkinson’s disease (PD). During the double-blind study period, prasinezumab-treated individuals showed less progression of motor signs (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS] Part III). We evaluated here whether the effect of prasinezumab on motor progression, assessed as change in MDS-UPDRS Part III in OFF- and ON-state, and MDS-UPDRS Part II scores was sustained over 4 years from the start of the trial. We compared participants enrolled in the PASADENA open-label extension (OLE) to an external comparator arm derived from the Parkinson's Progression Markers Initiative (PPMI) observational study. Both PASADENA delayed- (n = 94) and early-start (n = 177) groups showed a slower decline (less increase in score) on MDS-UPDRS Part III in OFF- (-51% for the delayed-start group and − 65% for the early-start group) and ON-state (-94% for the delayed-start group and − 118% for the early-start group), and on MDS-UPDRS Part II (-48% for the delayed-start group and − 40% for the early-start group), compared with the PPMI external comparator (n = 303). This exploratory analysis, which requires confirmation in future studies, suggests that the effect of prasinezumab in slowing motor progression in PD may be sustained long-term.