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- Title
Twice weekly dosing with Sebelipase alfa (Kanuma®) rescues severely ill infants with Wolman disease.
- Authors
de Castro, María José; Jones, Simon A; de las Heras, Javier; Sánchez-Pintos, Paula; Couce, María L; Colón, Cristóbal; Crujeiras, Pablo; Unceta, María; Church, Heather; Brammeier, Kathryn; Yee, Wu Hoi; Cooper, James; López de Frutos, Laura; Serrano-Gonzalo, Irene; Camba, María José; White, Fiona J.; Holmes, Victoria; Ghosh, Arunabha
- Abstract
Background: Sebelipase alfa (Kanuma®) is approved for patients with Wolman disease (WD) at a dosage of 3–5 mg/kg once weekly. Survival rates in the second of two clinical trials was greater, despite recruiting more severely ill patients, probably related to higher initial and maximal doses. We aimed to evaluate the effective pharmacokinetics and pharmacodynamics of Sebelipase alfa when administered to patients with severe WD at 5 mg/kg twice weekly, an intensive regimen which was not assessed in the trials. Methods: We recruited 3 patients receiving Sebelipase alfa 5 mg/kg twice weekly. We measured LAL activity in leukocytes and plasma oxysterol concentration in two patients and LAL activity in fibroblasts in one patient. Clinical follow up was also assessed. Results: Analyses of LAL activity and oxysterols demonstrate that there is short-lived enzyme activity post-dosing which is associated with the release of stored lipids. Clinical data demonstrate that 5 mg/kg twice weekly dosing is well tolerated and effective. Conclusion: 5 mg/kg twice weekly dosing with Sebelipase alfa rescues severely ill infants with WD by increasing substrate clearance. There is biologically relevant lipid accumulation in the 'trough' periods before the next dosing, even with this intensive regimen.
- Subjects
INFANT diseases; OXYSTEROLS; SURVIVAL rate; FIBROBLASTS; CLINICAL trials; ASSISTED suicide; ANIMAL rescue
- Publication
Orphanet Journal of Rare Diseases, 2024, Vol 19, Issue 1, p1
- ISSN
1750-1172
- Publication type
Article
- DOI
10.1186/s13023-024-03219-5