Article Text

Download PDFPDF
Real-world experience of gene therapy with onasemnogene-abeparvovec (Zolgensma®) for patients with SMA-type1 in UK
  1. Vasantha Gowda1,
  2. Elizabeth Wraige1,
  3. Min Ong2,
  4. Mark Atherton2,
  5. Anirban Majumdar3,
  6. Silvia Sanchez Marco3,
  7. Imelda Hughes4,
  8. Gary Mccullagh4,
  9. Francesco Muntoni5,
  10. Heinz Jungbluth,
  11. et al6
  1. 1Evelina London Children’s Hospital, London, UK
  2. 2Sheffield Children’s NHS Foundation Trust, Sheffield, UK
  3. 3Bristol Royal Hospital for Children, Bristol, UK
  4. 4Royal Manchester Children’s Hospital, Manchester, UK
  5. 5NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK
  6. 6Randall Centre for Cell and Molecular Biophysics, Muscle Signalling Section, Faculty of Life Scien

Abstract

Retrospective review of referrals to the National-Multidisciplinary-Team (NMDT) in England (& Wales), and of the clinical records of SMAtype1 patients included for Zolgensma® therapy in the UK.

Data was available for 42 patients: 13, 12, 10, 6, 1 from Evelina-London, Sheffield, Bristol, Manchester and Belfast centres respectively.

Patients’ age ranged from 2-months to 46-months and weights from 4.44kg to 13.5kg. Post-Zolgensma-infusion monitoring:

Most patients had asymptomatic thrombocytopaenia in week-1, resolving by week-2. No thrombotic microangiopathy was reported. Majority developed transient transaminitis with mild/moderate elevation of AST/ALT. Some had more severe/prolonged transaminitis – Liver ultrasound, coagulation-studies and clinical examination remained normal: 11 (weight>7.5kg) had ALT-peaks of >100 IU/L; 22 (15/22 weighed >7.5kg) had AST-peaks of >100 IU/L – good response seen to doubling Prednisolone, where indicated. Echocardiograms remained normal in patients with elevated Troponin-I levels; 4 had levels >100ng/l, prednisolone doubled in one, with good response.

13/42 needed doubling of Prednisolone; 12/13 had weight >7.5kg.

CHOP-INTEND scores post gene-therapy were available for 22/42. Scores improved in all patients except one (difficult assessment). Improvement ranged from 2-24 points.

Conclusion All patients tolerated the Zolgensma®-therapy well and have recovered well from any transient issues. No persistent complications from gene-therapy or steroid-cover were reported.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.