[en] [en] BACKGROUND: Long-term, real-world effectiveness and safety data of disease-modifying treatments for spinal muscular atrophy (SMA) are important for assessing outcomes and providing information for a larger number and broader range of SMA patients than included in clinical trials.
OBJECTIVE: We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting.
METHODS: RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources.
RESULTS: Recruitment started in September 2018. As of May 23, 2022, data were available for 168 patients treated with onasemnogene abeparvovec monotherapy. Median (IQR) age at initial SMA diagnosis was 1 (0-6) month and at onasemnogene abeparvovec infusion was 3 (1-10) months. Eighty patients (47.6%) had two and 70 (41.7%) had three copies of SMN2, and 98 (58.3%) were identified by newborn screening. Infants identified by newborn screening had a lower age at final assessment (mean age 11.5 months) and greater mean final (SD) CHOP INTEND score (57.0 [10.0] points) compared with clinically diagnosed patients (23.1 months; 52.1 [8.0] points). All patients maintained/achieved motor milestones. 48.5% (n = 81/167) experienced at least one treatment-emergent adverse event (AE), and 31/167 patients (18.6%) experienced at least one serious AE, of which 8/31 were considered treatment-related.
CONCLUSION: These real-world outcomes support findings from the interventional trial program and demonstrate effectiveness of onasemnogene abeparvovec over a large patient population, which was consistent with initial clinical data and published 5-year follow-up data. Observed AEs were consistent with the established safety profile of onasemnogene abeparvovec.
Disciplines :
Pediatrics
Author, co-author :
Servais, Laurent ; Université de Liège - ULiège > Département des sciences cliniques ; MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
Day, John W; Department of Neurology, Stanford University Medical Center, Stanford, CA, USA
De Vivo, Darryl C; Departments of Neurology and Pediatrics, Columbia University Irving Medical Center, New York, NY, USA
Kirschner, Janbernd; Department for Neuropediatrics and Muscle Disease, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
Mercuri, Eugenio; Department of Paediatric Neurology and Nemo Clinical Centre, Catholic University, Rome, Italy
Muntoni, Francesco; The Dubowitz Neuromuscular Centre, University College London, Great Ormond Street Institute of Child Health & Great Ormond Street Hospital, London, UK ; National Institute of Health Research, Great Ormond Street Hospital Biomedical Research Centre, London, UK
Proud, Crystal M; Children's Hospital of The King's Daughters, Norfolk, VA, USA
Shieh, Perry B; Department of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, USA
Tizzano, Eduardo F; Department of Clinical and Molecular Genetics, Hospital Vall d'Hebron, Barcelona, Spain
Quijano-Roy, Susana; Garches Neuromuscular Reference Center, Child Neurology and ICU Department, APHP Raymond Poincare University Hospital (UVSQ Paris Saclay), Garches, France
Desguerre, Isabelle; Hôpital Necker Enfants Malades, APHP, Paris, France
Saito, Kayoko; Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan
Faulkner, Eric; Novartis Gene Therapies, Inc., Bannockburn, IL, USA ; Institute for Precision and Individualized Therapy, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, IL, USA ; Genomics, Biotech and Emerging Medical Technology Institute, National Association of Managed Care Physicians, Richmond, VA, USA
Benguerba, Kamal M; Novartis Gene Therapies Switzerland GmbH, Rotkreuz, Switzerland
Raju, Dheeraj; Novartis Gene Therapies, Inc., Bannockburn, IL, USA
LaMarca, Nicole; Novartis Gene Therapies, Inc., Bannockburn, IL, USA
Sun, Rui; Novartis Gene Therapies, Inc., Bannockburn, IL, USA
Anderson, Frederick A; Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA, USA
Finkel, Richard S; Center for Experimental Neurotherapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA
Writing and editing assistance, including preparation of a draft manuscript under the direction and guidance of the authors, incorporating author feedback, and manuscript submission, was provided by Wynne Dillon, MS (Kay Square Scientific, Newtown Square, PA, USA) and David Wolff, MS (Novartis Gene Therapies, Inc., Bannockburn, IL, USA). This support was funded by Novartis Gene Therapies, Inc. Nicole Gusset of SMA Schweiz, Heimberg, Switzerland, and SMA Europe, Frieberg, Germany, was a member of the RESTORE steering committee and was part of the discussions that contributed to this analysis. The authors also wish to thank the investigators and site coordinators and, most importantly, all the patients, families, and caregivers for their willingness to participate in RESTORE, which is sponsored by Novartis Gene Therapies, Inc.
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