30 april 2024: Zie ook dit artikel: https://kanker-actueel.nl/q-10-werkt-ook-in-het-afremmen-van-de-ziekte-van-parkinson-40-procent-meer-remming-tov-controlegroep-blijkt-uit-driejarige-gerandomiseerde-studie.html

30 april 2024: Bron: Nature, Published: 15 April 2024

Prasinezumab, een zogeheten monoklonaal antilichaam dat alfa-synucleïne bindt, vertraagt de progressie van beginnende ziekte van Parkinson met meer dan 100 procent in vergelijking met beste zorg. Dat blijkt uit de tussenresultaten na 3 en een half jaar van de Pasadena studie, een driedubbel gerandomiseerde fase II studie, bij totaal 315 deelnemende patiënten met de ziekte van Parkinson in verschillende stadia.

Er werden drie groepen geanalyseerd. De oorspronkelijk behandelde groep kreeg een voortgezette therapie gedurende 2 jaar (vroege start), en de oorspronkelijke placebogroep kreeg het tweede jaar therapie, wat als een uitgestelde startgroep kan worden beschouwd. Na een wash-outperiode werden alle patiënten opgenomen in een open-label studie van 5 jaar. Een andere groep kwam in aanmerking voor controlegroep – een gematcht ‘real-world database’ van het Parkinson’s Progression Markers Initiative (PPMI).

In beide groepen waar patiënten werden behandeld met Prasinezumab vertoonden een indrukwekkend langzamere daling in de deel III-score vergeleken met de RWD-PPMI-groep. De groep met een vroege start had een 127% langzamere progressie, en de groep met een jaar later, dus een vertraagde start had een langzamere progressie maar noig altijd remde Prasinezumab de progressie van de ziekte met 96%.

Deze studie laat dus een veelbelovend effect zien op het vertragen van de progressie van de ziekte van Parkinson aldus de onderzoekers en het zou heel goed kunnen zijn dat het effect duidelijker wordt naarmate het type therapie in de loop van de jaren wordt bekeken. Probleem is dat de gegevens van de controlegroep bestond uit gegevens uit een ander onderzoek en die behandeling was open-label. Open-label onderzoeken zijn misleidend bij de ziekte van Parkinson, gezien de grote placebo-effecten.

Zoals de auteurs opmerkten, moet er een gerandomiseerde, gecontroleerde studie worden uitgevoerd. Maar als daarin de resultaten uit de Pasadena studie daarin zouden worden bevestigd, ondersteunt dit ook het idee dat alfa-synucleïne inderdaad mede oorzaak van de ziekte van Parkinson is.

Het volledige studierapport is redent gepubliceerd in Nature en gratis in te zien of te downloaden. Klik daarvoor op de titel van het abstract:

Article
Open access
Published: 15 April 2024

Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson’s disease

Nature Medicine volume 30, pages1096–1103 (2024)Cite this article

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Abstract

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.

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Data availability

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.

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Acknowledgements

The study is sponsored by F. Hoffmann-La Roche Ltd. F. Hoffmann-La Roche Ltd was involved in the study design, collection, analysis, interpretation of data, the writing of this article and the decision to submit it for publication. We thank the patients and their families who participated in the study and the clinical investigators. Editorial assistance for this manuscript was provided by mXm Medical Communications funded by F. Hoffmann-La Roche Ltd.

Author information

Authors and Affiliations

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

Gennaro Pagano, Kirsten I. Taylor, Hanno Svoboda, Geoffrey A. Kerchner, Patrik Brundin & Azad Bonni
University of Exeter Medical School, London, UK

Gennaro Pagano
Roche Products Ltd, Welwyn Garden City, UK

Judith Anzures Cabrera & Dylan Trundell
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Tanya Simuni
Institute for Neurodegenerative Disorders, New Haven, CT, USA

Kenneth Marek
Department of Neurology, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

Ronald B. Postuma
Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne, UK

Nicola Pavese
The Institute for Research and Medical Care (IRCCS) San Raffaele Pisana, University San Raffaele Roma, Rome, Italy

Fabrizio Stocchi
Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany

Kathrin Brockmann
Roche Diagnostics GmbH, Penzberg, Germany

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

Annabelle Monnet, Rachelle Doody, Paulo Fontoura & Tania Nikolcheva

Consortia

PASADENA Investigators

Tanya Simuni
& Kathrin Brockmann

Prasinezumab Study Group

Gennaro Pagano
, Kirsten I. Taylor
, Judith Anzures Cabrera
, Hanno Svoboda
, Dylan Trundell
, Annabelle Monnet
, Rachelle Doody
, Paulo Fontoura
, Geoffrey A. Kerchner
, Patrik Brundin
, Tania Nikolcheva
, Tania Nikolcheva
& Azad Bonni

Contributions

G.P., K.I.T. and J.A.C. were responsible for the study concept and design. G.P., K.I.T., J.A.C., T.S., K.M., R.B.P., N.P., F.S., K.B., H.S., D.T., A.M., R.D., P.F., G.A.K., P.B., T.N. and A.B. undertook acquisition, analysis or interpretation of the data. G.P., K.I.T. and J.A.C. drafted the manuscript. G.P., K.I.T., J.A.C., T.S., K.M., R.B.P., N.P., F.S., K.B., H.S., D.T., A.M., R.D., P.F., G.A.K., P.B., T.N. and A.B. were responsible for critical revision and final approval of the manuscript.

Corresponding author

Correspondence to Gennaro Pagano.

Ethics declarations

Competing interests

G.P., K.I.T., A.M., R.D., P.F., G.A.K., P.B., T.N. and A.B. are employees and shareholders of F. Hoffmann-La Roche Ltd. R.D. is also employed by Genentech. P.B. also has ownership interests in Acousort AB, Enterin Inc., Axial Therapeutics and Ryne Bio. J.A.C. and D.T. are employees of Roche Products Ltd and shareholders of F. Hoffmann-La Roche Ltd. H.S. is an employee of Roche Diagnostics GmbH Deutschland and a shareholder of F. Hoffmann-La Roche. In the past 12 months, T.S. has served as a consultant for AskBio, Amneal, Blue Rock Therapeutics, Critical Path for Parkinson’s Consortium, Denali, General Electric, Kyowa, NeuroDerm/Mitsubishi Tanabe Pharma America Inc. (MTPA), Prevail/Lilly, Roche, Sanofi, Sinopia, Takeda and Vanqua Bio. T.S. served on advisory boards for AskBio, Amneal, Biohaven, Denali, GAIN, General Electric, Kyowa, Michael J. Fox Foundation for Parkinson’s Research (MJFF), Neuron23, Parkinson Study Group, Prevail/Lilly and Roche. T.S. has also served as a member of the scientific advisory board of Koneksa, NeuroDerm/MTPA, Sanofi and UCB, has received research funding from Amneal, Biogen, NeuroDerm, Prevail, Roche and UCB and is an investigator for NINDS, MJFF, Parkinson’s Foundation. K.M. is a consultant for MJFF, F. Hoffmann-La Roche Ltd, UCB, Denali, Takeda, Biohaven, Neuron23, Aprinoia, Prothena, Calico, Inhibikase, Invicro, Koneksa and Lilly. R.B.P. reports grants and personal fees from Fonds de la Recherche en Sante, grants from Canadian Institute of Health Research, grants from MJFF, grants from Webster Foundation, personal fees from Biogen, personal fees from Curasen, personal fees from Novartis, personal fees from Eisai, others from Parkinson Canada, grants from National Institute of Health, personal fees from International Parkinson and Movement Disorders Society, personal fees from Merck, personal fees from Vaxxinity, personal fees from Bristol Myers Squibb, personal fees from Clinilabs, personal fees from Ventus, personal fees from Korro and personal fees from Calico. R.B.P. also received consulting fees from Roche for helping plan and interpret the study. N.P. reports participating in advisory boards for Britannia, Boston Scientific, Benevolent AI, Hoffmann-La Roche, Inc. and AbbVie. N.P. also reports receiving honoraria from Britannia, AbbVie, GE Healthcare and Boston Scientific, and grants from the Independent Research Fund Denmark, Danish Parkinson’s Disease Association, Parkinson’s UK, Center of Excellence in Neurodegeneration network award, GE Healthcare Grant, Multiple System Atrophy Trust, Weston Brain Institute, European Union (EU) Joint Program Neurodegenerative Disease Research, EU Horizon 2020 research and Hoffmann-La Roche, Inc. F.S. is a consultant for AbbVie, Bial Pharma, Biogen, F. Hoffmann-La Roche Ltd, H. Lundbeck A S, Mitsubishi Tanabe Pharma America, Inc., Sunovion Pharmaceuticals, Inc., Teva Pharmaceutical Industries, Zambon and Britannia. K.B. has received research funding from the MJFF, the German Society for Parkinsonʼs DPG, the Health Forum Baden Wuerttemberg, the Else Kröner Fresenius Stiftung, the University of Tübingen and from the German Research Foundation DFG. K.B. is a consultant for F. Hoffmann-La Roche Ltd, Vanqua Bio and the MJFF, and has received speaker honoraria from AbbVie, Lundbeck, UCB and Zambon.

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Nature Medicine thanks David Devos, Michael Schwarzchild and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Jerome Staal, in collaboration with the Nature Medicine team.

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Supplementary information

Supplementary Information

Supplementary materials, Tables 1–7 and Fig. 1.

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