Onasemnogene abeparvovec preserves bulbar function in infants with presymptomatic spinal muscular atrophy: a post-hoc analysis of the SPR1NT trial.

Autor: Shell RD; Nationwide Children's Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University, Columbus, OH, USA. Electronic address: richard.shell@nationwidechildrens.org., McGrattan KE; University of Minnesota, Minneapolis, MN, USA., Hurst-Davis R; Primary Children's Hospital, Salt Lake City, UT, USA., Young SD; Stanford University School of Medicine, Stanford, CA, USA., Baranello G; The Dubowitz Neuromuscular Centre, Developmental Neuroscience Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre & Great Ormond Street Hospital NHS Foundation Trust, London, UK., Lavrov A; Novartis Gene Therapies, Inc., Cambridge, UK., O'Brien E; Novartis, Dublin, Ireland., Wallach S; Novartis Gene Therapies, Inc., Bannockburn, IL, USA., LaMarca N; Novartis Gene Therapies, Inc., Bannockburn, IL, USA., Reyna SP; Novartis Gene Therapies, Inc., Bannockburn, IL, USA., Darras BT; Boston Children's Hospital, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Neuromuscular disorders : NMD [Neuromuscul Disord] 2023 Aug; Vol. 33 (8), pp. 670-676. Date of Electronic Publication: 2023 Jun 22.
DOI: 10.1016/j.nmd.2023.06.005
Abstrakt: Bulbar function in spinal muscular atrophy has been defined as the ability to meet nutritional needs by mouth while maintaining airway protection and communicate verbally. The effects of disease-modifying treatment on bulbar function are not clear. A multidisciplinary team conducted post-hoc analyses of phase 3 SPR1NT trial data to evaluate bulbar function of infants at risk for spinal muscular atrophy who received one-time gene replacement therapy (onasemnogene abeparvovec) before symptom onset. Three endpoints represented adequate bulbar function in SPR1NT: (1) absence of physiologic swallowing impairment, (2) full oral nutrition, and (3) absence of adverse events indicating pulmonary instability. Communication was not assessed in SPR1NT. We descriptively assessed numbers/percentages of children who achieved each endpoint and all three collectively. SPR1NT included infants <6 postnatal weeks with two (n = 14) or three (n = 15) copies of the survival motor neuron 2 gene. At study end (18 [two-copy cohort] or 24 [three-copy cohort] months of age), 100% (29/29) of patients swallowed normally, achieved full oral nutrition, maintained pulmonary stability, and achieved the composite endpoint. When administered to infants before clinical symptom onset, onasemnogene abeparvovec allowed children at risk for spinal muscular atrophy to achieve milestones within published normal ranges of development and preserve bulbar function.
Competing Interests: Declaration of Competing Interest Richard D. Shell has been a paid speaker for Novartis Gene Therapies. Katlyn E. McGrattan has received research grants from the National Institutes of Health, National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, 1R41HD104305-01 on “A novel non-invasive method of aspiration detection in preterm infants (Ongoing).” In addition, she is a consultant for Novartis Gene Therapies, Biogen, and Roche. Rebecca Hurst-Davis is a Cure SMA Medical Advisory Council member. Sally Dunaway Young is an advisory board member/consultant for Biogen, Cure SMA, Genentech/Roche, and Scholar Rock, and receives grant support from Novartis Gene Therapies, Inc., Biogen, Cure SMA, Genentech/Roche, Genzyme, Minoryx, PTC Therapeutics, and Scholar Rock. Giovanni Baranello has received speaker and consulting fees from Biogen, Novartis Gene Therapies, Inc. (AveXis), and Roche, and has worked as a principal investigator of SMA studies sponsored by Novartis Gene Therapies, Inc., and Roche. Arseniy Lavrov, Eamonn O'Brien, Shiri Wallach, Nicole LaMarca, and Sandra P. Reyna are employees of Novartis Gene Therapies and hold stock/other equities. Basil T. Darras has served as an ad-hoc scientific advisory board member for Audentes, AveXis/Novartis Gene Therapies, Biogen, Pfizer, Sarepta, Roche/Genentech, and Vertex; as a steering committee chair and member for the Roche FIREFISH and Biogen ASCEND studies, respectively, and data and safety monitoring board member for Amicus Inc.; he has no financial interests in these companies. He has received research support from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the Slaney Family Fund for SMA, the Spinal Muscular Atrophy Foundation, CureSMA, and Summit and Working on Walking Fund and has received grants from Ionis Pharmaceuticals, Inc., for the ENDEAR, CHERISH, CS2/CS12 studies; from Biogen for CS11; and from Novartis Gene Therapies, Inc., Sarepta Pharmaceuticals, Novartis, PTC Therapeutics, Roche, Scholar Rock, and Fibrogen. He has also received royalties for books and online publications from Elsevier and UpToDate, Inc.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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