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

Author:

Servais Laurent1,Day John W.2,De Vivo Darryl C.3,Kirschner Janbernd4,Mercuri Eugenio5,Muntoni Francesco67,Proud Crystal M.8,Shieh Perry B.9,Tizzano Eduardo F.10,Quijano-Roy Susana11,Desguerre Isabelle12,Saito Kayoko13,Faulkner Eric141516,Benguerba Kamal M.17,Raju Dheeraj14,LaMarca Nicole14,Sun Rui14,Anderson Frederick A.18,Finkel Richard S.19

Affiliation:

1. 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

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

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

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

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

6. The Dubowitz Neuromuscular Centre, University College London, Great Ormond Street Institute of Child Health & Great Ormond Street Hospital, London, UK

7. National Institute of Health Research, Great Ormond Street Hospital Biomedical Research Centre, London, UK

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

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

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

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

12. Hôpital Necker Enfants Malades, APHP, Paris, France

13. Institute of Medical Genetics, Tokyo Women’s Medical University, Tokyo, Japan

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

15. Institute for Precision and Individualized Therapy, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, IL, USA

16. Genomics, Biotech and Emerging Medical Technology Institute, National Association of Managed Care Physicians, Richmond, VA, USA

17. Novartis Gene Therapies Switzerland GmbH, Rotkreuz, Switzerland

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

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

Abstract

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.

Publisher

IOS Press

Subject

Neurology (clinical),Neurology

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