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Lookup NU author(s): Professor Nicola PaveseORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024. Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson’s disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). We report here an exploratory analysis assessing whether prasinezumab showed greater benefits on motor signs progression in prespecified subgroups with faster motor progression. Prasinezumab’s potential effects on disease progression were assessed in four prespecified and six exploratory subpopulations of PASADENA: use of monoamine oxidase B inhibitors at baseline (yes versus no); Hoehn and Yahr stage (2 versus 1); rapid eye movement sleep behavior disorder (yes versus no); data-driven subphenotypes (diffuse malignant versus nondiffuse malignant); age at baseline (≥60 years versus <60 years); sex (male versus female); disease duration (>12 months versus <12 months); age at diagnosis (≥60 years versus <60 years); motor subphenotypes (akinetic–rigid versus tremor-dominant); and motor subphenotypes (postural instability gait dysfunction versus tremor-dominant). In these subpopulations, the effect of prasinezumab on slowing motor signs progression (MDS-UPDRS Part III) was greater in the rapidly progressing subpopulations (for example, participants who were diffuse malignant or taking monoamine oxidase B inhibitors at baseline). This exploratory analysis suggests that, in a trial of 1-year duration, prasinezumab might reduce motor progression to a greater extent in individuals with more rapidly progressing Parkinson’s disease. However, because this was a post hoc analysis, additional randomized clinical trials are needed to validate these findings.
Author(s): Pagano G, Taylor KI, Anzures Cabrera J, Simuni T, Marek K, Postuma RB, Pavese N, Stocchi F, Brockmann K, Svoboda H, Trundell D, Monnet A, Doody R, Fontoura P, Kerchner GA, Brundin P, Nikolcheva T, Bonni A, PASADENA Investigators, Prasinezumab Study Group
Publication type: Article
Publication status: Published
Journal: Nature Medicine
Year: 2024
Volume: 30
Issue: 4
Pages: 1096-1103
Online publication date: 15/04/2024
Acceptance date: 23/02/2024
Date deposited: 30/04/2024
ISSN (print): 1078-8956
ISSN (electronic): 1546-170X
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41591-024-02886-y
DOI: 10.1038/s41591-024-02886-y
Data Access Statement: Qualified researchers may request access to individual patient-level data through the clinical study data request platform (https://vivli. org/). Further details on Roche’s criteria for eligible studies are available at https://vivli.org/members/ourmembers/. For further details on Roche’s Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see: https://www. roche.com/research_and_development/who_we_are_how_we_work/ clinical_trials/our_commitment_to_data_sharing.htm
PubMed id: 38622249
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