European ad-hoc consensus statement on gene replacement therapy for spinal muscular atrophy.

Spinal muscular atrophy (SMA) used to be one of the most common genetic causes of infant mortality. New disease modifying treatments have changed the disease trajectories and most impressive results are seen if treatment is initiated in the presymptomatic phase of the disease. Very recently, the European Medicine Agency approved Onasemnogene abeparvovec (Zolgensma®) for the treatment of patients with SMA with up to three copies of the SMN2 gene or the clinical presentation of SMA type 1. While this broad indication provides new opportunities, it also triggers discussions on the appropriate selection of patients in the context of limited available evidence. To aid the rational use of Onasemnogene abeparvovec for the treatment of SMA, a group of European neuromuscular experts presents in this paper eleven consensus statements covering qualification, patient selection, safety considerations and long-term monitoring.

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Copyright © 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest For the work presented here the authors did not receive any financial or other material support. Outside the submitted work authors declare the following potential conflicts of interest. Janbernd Kirschner received honoraria for participation in advisory boards and educational activities from Avexis, Biogen, Roche, and ScholarRock. He received funding for clinical research from Biogen and AveXis. Nina Butoianu – nothing to disclose. Nathalie Goemans: participated in ad hoc advisory board activities for Biogen, Avexis, Roche and has received speaker's fee for participation in symposia from Roche and Biogen. Jana Haberlova participated in advisory board activities and has received speaker's fee for participation in symposia for Biogen, Novartis and Roche. Anna Kostera-Pruszczyk reports advisory board for Biogen, Avexis/Novartis, Roche, PTC, and grant support from Biogen, travel support from Biogen and Roche. Eduardo F. Tizzano reports grant support to conduct clinical trials on SMA from Ionis/Biogen. Serves as a consultant to AveXis, Biogen, Biologix, Cytokinetics, Roche for participation to scientific advisory boards and participation in educational symposia. Eugenio Mercuri reports acting as a consultant for AveXis, Biogen, Roche, Novartis, Cytokinetics and Scholar Rock; receiving honoraria from AveXis, Biogen, Roche, for participation to scientific advisory boards and participation in educational symposia; receiving investigator grant from Biogen for the iSMAc disease registry; acting as Principal investigator for Ionis/Biogen nusinersen trials; Roche olesoxime and risdiplam trial, Scholar Rock and Avexis zolgesma trials, all in SMA. Susana Quijano-Roy participated in and received honoraria for lectures and advisory board activities for Biogen, Avexis, and Roche. Thomas Sejersen: participated in and received honoraria for lectures and advisory board activities for Biogen, Avexis, and Roche. W. Ludo van der Pol participated in ad hoc advisory board activities for Biogen and Avexis and served as a member of the Data Monitoring Committee for Branaplam (Novartis). Principal investigator for Jewelfish (Roche) and Topaz studies (Scholar Rock) and member of the scientific advisory board for SMA Europe. Andreas Ziegler reports personal fees and scientific funding from Biogen, personal fees from Avexis, outside the submitted work. Laurent Servais reports research support from AveXis, Roche and Biogen, and consultancy fees/board member of Avexis, Biogen, Roche and Cytokinetics. Francesco Muntoni reports serving on the Pfizer Rare Diseases advisory board; acting as a consultant for AveXis, Biogen, Roche, Novartis; receiving honoraria from AveXis, Biogen, Roche, for participation to scientific advisory boards and participation in educational symposia; receiving investigator grant from Biogen for SMA REACH UK registry; acting as Principal investigator for Ionis/Biogen nusinersen trials; Roche olesoxime and risdiplam trial and Avexis zolgesma trials, all in SMA.