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Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy.
D'Silva, Arlene M; Holland, Sandra; Kariyawasam, Didu; Herbert, Karen; Barclay, Peter; Cairns, Anita; MacLennan, Suzanna C; Ryan, Monique M; Sampaio, Hugo; Smith, Nicholas; Woodcock, Ian R; Yiu, Eppie M; Alexander, Ian E; Farrar, Michelle A.
  • D'Silva AM; Department of Neurology, Sydney Children's Hospital Network, Sydney, New South Wales, Australia.
  • Holland S; School of Clinical Medicine, UNSW Medicine & Health, Randwick Clinical Campus, Discipline of Paediatrics, University of New South Wales, Sydney, New South Wales, Australia.
  • Kariyawasam D; Department of Neurology, Sydney Children's Hospital Network, Sydney, New South Wales, Australia.
  • Herbert K; Department of Neurology, Sydney Children's Hospital Network, Sydney, New South Wales, Australia.
  • Barclay P; School of Clinical Medicine, UNSW Medicine & Health, Randwick Clinical Campus, Discipline of Paediatrics, University of New South Wales, Sydney, New South Wales, Australia.
  • Cairns A; Physiotherapy, Sydney Children's Hospital, Sydney, New South Wales, Australia.
  • MacLennan SC; Department of Pharmacy, Prince of Wales Hospital, Sydney Children's Hospital Randwick and The Royal Hospital for Women, Randwick, New South Wales, Australia.
  • Ryan MM; Neurosciences Department, Queensland's Children Hospital, South Brisbane, Queensland, Australia.
  • Sampaio H; Neurology Department, Women's & Children's Hospital, North Adelaide, South Australia, Australia.
  • Smith N; School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia.
  • Woodcock IR; Department of Neurology, Royal Children's Hospital, Melbourne, Australia.
  • Yiu EM; Neuroscience Research Group, Murdoch Children's Research Institute, Melbourne, Australia.
  • Alexander IE; Department of Paediatrics, The University of Melbourne, Melbourne, Australia.
  • Farrar MA; Department of Neurology, Sydney Children's Hospital Network, Sydney, New South Wales, Australia.
Ann Clin Transl Neurol ; 9(3): 339-350, 2022 03.
Article in English | MEDLINE | ID: covidwho-1750288
ABSTRACT

OBJECTIVE:

To provide a greater understanding of the tolerability, safety and clinical outcomes of onasemnogene abeparvovec in real-world practice, in a broad population of infants with spinal muscular atrophy (SMA).

METHODS:

A prospective cohort study of children with SMA treated with onasemnogene abeparvovec at Sydney Children's Hospital Network, Australia was conducted from August 2019 to November 2021. Safety outcomes included clinical and laboratory evaluations. Efficacy assessments included World Health Organisation (WHO) motor milestones, oral and swallowing abilities, and requirements for respiratory support. The implementation of a model of care for onasemnogene abeparvovec administration in health practice is described.

RESULTS:

21 children were treated (age range, 0.65-24 months; body weight range, 2.5-12.5 kg) and 19/21 (90.4%) had previous nusinersen. Transient treatment-related side effects occurred in all children; vomiting (100%), transaminitis (57%) and thrombocytopaenia (33%). Incidence of moderate/severe transaminitis was significantly greater in infants weighing ≥8 kg compared with <8 kg (p < 0.05). Duration of prednisolone following treatment was prolonged (mean 87.5 days, range 57-274 days). 16/21 (76%) children gained at least one WHO motor milestone. Stabilisation or improvement in bulbar or respiratory function was observed in 20/21 (95.2%) patients. Implementation challenges were mitigated by developing standard operating procedures and facilitating exchange of knowledge.

INTERPRETATION:

This study provides real-world evidence to inform treatment decisions and guide therapeutic expectations for onasemnogene abeparvovec and combination therapy for SMA in health practice, especially for children weighing ≥8 kg receiving higher vector loads. Proactive clinical and laboratory surveillance is essential to facilitate individualised management of risks.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Muscular Atrophy, Spinal / Spinal Muscular Atrophies of Childhood / Drug-Related Side Effects and Adverse Reactions Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Limits: Child / Child, preschool / Humans / Infant / Infant, Newborn Country/Region as subject: Oceania Language: English Journal: Ann Clin Transl Neurol Year: 2022 Document Type: Article Affiliation country: Acn3.51519

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Muscular Atrophy, Spinal / Spinal Muscular Atrophies of Childhood / Drug-Related Side Effects and Adverse Reactions Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Limits: Child / Child, preschool / Humans / Infant / Infant, Newborn Country/Region as subject: Oceania Language: English Journal: Ann Clin Transl Neurol Year: 2022 Document Type: Article Affiliation country: Acn3.51519