Real-World Outcomes in Patients with Spinal Muscular Atrophy Treated with Onasemnogene Abeparvovec Monotherapy: Findings from the RESTORE Registry.

AAV9 vector-based gene replacement therapy RESTORE registry long-term follow-up motor neuron disease newborn screening onasemnogene abeparvovec outcomes rare disease real-world evidence spinal muscular atrophy

Journal

Journal of neuromuscular diseases
ISSN: 2214-3602
Titre abrégé: J Neuromuscul Dis
Pays: Netherlands
ID NLM: 101649948

Informations de publication

Date de publication:
18 Jan 2024
Historique:
medline: 22 1 2024
pubmed: 22 1 2024
entrez: 22 1 2024
Statut: aheadofprint

Résumé

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. We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting. RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources. 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. 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.

Sections du résumé

BACKGROUND 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 OBJECTIVE
We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting.
METHODS METHODS
RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources.
RESULTS 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 CONCLUSIONS
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.

Identifiants

DOI: 10.3233/JND-230122 PMID: 38250783
pubmed: 38250783
pii: JND230122
doi: 10.3233/JND-230122
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Auteurs

Laurent Servais (L)

MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liège, Liège, Belgium.

John W Day (JW)

Department of Neurology, Stanford University Medical Center, Stanford, CA, USA.

Darryl C De Vivo (DC)

Departments of Neurology and Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.

Janbernd Kirschner (J)

Department for Neuropediatrics and Muscle Disease, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.

Eugenio Mercuri (E)

Department of Paediatric Neurology and Nemo Clinical Centre, Catholic University, Rome, Italy.

Francesco Muntoni (F)

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.

Crystal M Proud (CM)

Children's Hospital of The King's Daughters, Norfolk, VA, USA.

Perry B Shieh (PB)

Department of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, USA.

Eduardo F Tizzano (EF)

Department of Clinical and Molecular Genetics, Hospital Vall d'Hebron, Barcelona, Spain.

Susana Quijano-Roy (S)

Garches Neuromuscular Reference Center, Child Neurology and ICU Department, APHP Raymond Poincare University Hospital (UVSQ Paris Saclay), Garches, France.

Isabelle Desguerre (I)

Hôpital Necker Enfants Malades, APHP, Paris, France.

Kayoko Saito (K)

Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.

Eric Faulkner (E)

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.

Kamal M Benguerba (KM)

Novartis Gene Therapies Switzerland GmbH, Rotkreuz, Switzerland.

Dheeraj Raju (D)

Novartis Gene Therapies, Inc., Bannockburn, IL, USA.

Nicole LaMarca (N)

Novartis Gene Therapies, Inc., Bannockburn, IL, USA.

Rui Sun (R)

Novartis Gene Therapies, Inc., Bannockburn, IL, USA.

Frederick A Anderson (FA)

Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA, USA.

Richard S Finkel (RS)

Center for Experimental Neurotherapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.

Classifications MeSH