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

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
08 Oct 2024
Historique:
received: 07 04 2024
accepted: 27 08 2024
medline: 9 10 2024
pubmed: 9 10 2024
entrez: 8 10 2024
Statut: aheadofprint

Résumé

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 .

Identifiants

DOI: 10.1038/s41591-024-03270-6 PMID: 39379705
pubmed: 39379705
doi: 10.1038/s41591-024-03270-6
pii: 10.1038/s41591-024-03270-6
doi:

Banques de données

ClinicalTrials.gov
['NCT03100149']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s).

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Auteurs

Gennaro Pagano (G)

Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland. gennaro.pagano@roche.com.
University of Exeter Medical School, London, UK. gennaro.pagano@roche.com.
ORCID: 0000-0002-6247-8988

Annabelle Monnet (A)

F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Adriana Reyes (A)

F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Benjamin Ribba (B)

Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland.

Hanno Svoboda (H)

Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland.
Roche Diagnostics GmbH, Penzberg, Germany.
ORCID: 0009-0005-1910-586X

Thomas Kustermann (T)

Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland.

Tanya Simuni (T)

Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Ronald B Postuma (RB)

Department of Neurology, McGill University and Montreal Neurological Institute, Montreal, Quebec, Canada.

Nicola Pavese (N)

Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne, UK.

Fabrizio Stocchi (F)

University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome, Italy.

Kathrin Brockmann (K)

Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases (DZNE), University of Tuebingen, Tuebingen, Germany.
ORCID: 0000-0002-7515-8596

Krzysztof Smigorski (K)

Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland.

Valentina Gerbaldo (V)

Excelya Germany GmbH, Freiburg, Germany.

Paulo Fontoura (P)

F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Rachelle Doody (R)

F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Genentech USA Inc., San Francisco, CA, USA.

Geoffrey A Kerchner (GA)

Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland.

Patrik Brundin (P)

Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland.

Kenneth Marek (K)

Institute for Neurodegenerative Disorders, New Haven, CT, USA.

Azad Bonni (A)

Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland.

Tania Nikolcheva (T)

F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Classifications MeSH