Delphi consensus on gene therapy of spinal muscular atrophy with onasemnogene abeparvovec in Germany, Austria and Switzerland—part I—systematic literature review and existing evidence
Year: 2025
Type: review
Abstract: BackgroundSince the approval of onasemnogen abeparvovec (OA) for gene addition therapy in children with spinal muscular atrophy (SMA), there has been a considerable increase of evidence regarding its effectiveness and safety. Consequently, the previous recommendations needed to be revised.ObjectiveThe primary objective was to develop an evidence- and expert-based best practice protocol ensuring optimal patient safety and comprehensive support for affected families. The harmonization of treatment algorithms is expected to facilitate the collection of standardized real-world data, laying the foundation for future evidence-based adjustments.MethodsA modified, two-part Delphi process was selected as a standardized methodology. Experts specializing in SMA from all 31 neuromuscular treatment centers within Germany, Austria and Switzerland, and patient advocacy groups participated in an industry-independent Delphi panel. Existing evidence concerning effectiveness, safety, and guidelines of OA was analyzed in a systematic literature followed by development of consensus statements regarding its effectiveness.ResultsStrong consensus was reached regarding the following statements on effectiveness: (1) OA gene addition therapy for SMA demonstrates a clear advantage compared to the natural progression of the disease. (2) Superiority of any of the three approved disease-modifying therapies has not been proven. (3) Earlier initiation of therapy with fewer symptoms and shorter disease duration leads to better outcomes. (4) There is no clinical evidence supporting the superiority of combining two treatments over monotherapy.Conclusions: The systematic literature analysis constitutes the basis for the subsequent part 2, which involves the generation of expert-based recommendations for the surveillance of SMA gene addition therapy.
Authors: Claudia Weiß, Katharina Vill, Matthias Baumann, Günther Bernert, Astrid Blaschek, Astrid Eisenkölbl, Marina Flotats-Bastardas, Johannes Friese, Claudia Ganter, Klaus Goldhahn, Andreas Hahn, Maja von der Hagen, Hans Hartmann, Oswald Hasselmann, Veronka Horber, Ralf A Husain, Sabine Illsinger, David Jacquier, Jessika Johannsen, Cornelia Köhler, Heike Kölbel, Michael Kolodzig, Andrea Klein, Astrid Pechmann, Arpad von Moers, Wolfgang Müller-Felber, Christian Rauscher, Ulrike Schara-Schmidt, Gudrun Schreiber, Oliver Schwartz, Joachim Sproß, Georg M Stettner, Corinna Stoltenburg, Eva Stumpe, Regina Trollmann, Gert Wiegand, Ekkehard Wilichowski, Janbernd Kirschner, Andreas Ziegler
Institutions: Charité - Universitätsmedizin Berlin, Ludwig-Maximilians-Universität München, Innsbruck Medical University, Johannes Kepler University of Linz, Saarland University, University Hospital Bonn, Heidelberg University, Universitätsklinikum Gießen und Marburg, Technische Universität Dresden, Medizinische Hochschule Hannover, Ostschweizer Kinderspital, Jena University Hospital, Centre Hospitalier Universitaire Vaudois, University Medical Center Hamburg-Eppendorf, University Hospitals of the Ruhr-University of Bochum, University of Duisburg-Essen, Staatliche Hochschule für Gestaltung Karlsruhe, University of Bern, University Hospital of Bern, University of Freiburg, University Medical Center Freiburg, Paracelsus Medical University, Klinikum Kassel, University Hospital Münster, Deutsche Gesellschaft für Muskelkranke, University of Zurich, University Children's Hospital Zurich, Friedrich-Alexander-Universität Erlangen-Nürnberg, Asklepios, Asklepios Kliniken Hamburg, Universitätsmedizin Göttingen
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funder: Gemeinsame Bundesausschuss
Award: G4023440861
OpenAlex ID: W4416581704