Exploratory Analysis of PASADENA Open-label Extension Evaluating the Effect of Prasinezumab on the Progression of Motor Signs and Symptoms
Gennaro Pagano1, Annabelle Monnet2, Adriana Reyes2, Tanya Simuni3, Ronald Postuma4, Nicola Pavese5, Fabrizio Stocchi6, Krzysztof Smigorski1, Valentina Gerbaldo7, Riorge Thomas8, Hanno Svoboda9, Paulo Fontoura2, Rachelle Doody2, Geoffrey Kerchner1, Patrik Brundin1, Azad Bonni1, Kenneth Marek10, Tania Nikolcheva2
1Roche Pharma Research and Early Development (pRED), F. Hoffmann-La Roche Ltd, 2F. Hoffmann-La Roche Ltd, 3Northwestern University Feinberg School of Medicine, 4Montreal General Hospital, 5Newcastle University, 6Institute for Research and Medical Care, IRCCS San Raffaele Pisana, 7Excelya Germany GmbH, 8Roche Products Ltd, Welwyn Garden City, UK, 9Roche Diagnostics GmbH, DE, 10Invicro, A Konica Minolta Company
Objective:
To compare the progression of the PASADENA population treated with prasinezumab to a matched real-world data sample from the Parkinson's Progression Markers Initiative (RWD-PPMI).
Background:
Prasinezumab is a humanized monoclonal antibody that binds aggregated alpha-synuclein with the potential to slow disease progression in Parkinson’s disease (PD).
Design/Methods:
Early-stage PD participants of PASADENA received intravenous prasinezumab every 4 weeks (1500 mg or 4500 mg) for 104 weeks (early-start group) or placebo for 52 weeks (Part 1) followed by prasinezumab (1500 mg or 4500 mg) for 52 weeks (Part 2; delayed-start group). Following a wash-out period on average 7.4 months, 271 participants entered the 5-year open-label extension (OLE) receiving prasinezumab 1500 mg every 4 weeks (Part 3) and were included in the analysis, regardless of change in symptomatic therapy. After 3.5 years follow-up, MDS-UPDRS part III ON-state and MDS-UPDSR part II score were compared among early-start group (n=177), delayed-start group (n=94) and RWD-PPMI (n=303), using a mixed model for repeated measures.
Results:
Compared to the RWD-PPMI, PASADENA delayed- and early-start groups showed a slower decline (less increase in score) on MDS-UPDRS Part III ON-state: delayed-start group: -96% less progression (mean points [80% confidence interval]) (-4.9 [-6.75 to -3.04]), early-start group: -127% less progression (-6.5 [-7.96 to -5.03]); and on MDS-UPDRS Part II: delayed-start group: -38% less progression (-1.53 [-2.31 to -0.74]), early-start group: -43% less progression (-1.73 [-2.36 to -1.11]).
Conclusions:
Progression in the PASADENA OLE population was relatively small compared to the RWD-PPMI cohort, suggesting that prasinezumab slowed the progression of motor signs and symptoms of PD. These exploratory results need to be confirmed in a randomized controlled trial.