Survival in infants treated with sebelipase Alfa for lysosomal acid lipase deficiency: an open-label, multicenter, dose-escalation study


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Jones S. A. , Rojas-Caro S., Quinn A. G. , Friedman M., Marulkar S., Ezgu F., ...More

ORPHANET JOURNAL OF RARE DISEASES, vol.12, 2017 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 12
  • Publication Date: 2017
  • Doi Number: 10.1186/s13023-017-0587-3
  • Title of Journal : ORPHANET JOURNAL OF RARE DISEASES
  • Keywords: Lysosomal acid lipase deficiency, Wolman disease, Sebelipase alfa, Survival, Hemophagocytic lymphohistiocytosis, ESTER STORAGE DISEASE, BONE-MARROW-TRANSPLANTATION, WOLMAN-DISEASE, CELL TRANSPLANTATION, MUTATION

Abstract

Background: Infants presenting with lysosomal acid lipase deficiency have marked failure to thrive, diarrhea, massive hepatosplenomegaly, anemia, rapidly progressive liver disease, and death typically in the first 6 months of life; the only available potential treatment has been hematopoietic stem cell transplantation, which is associated with high morbidity and mortality in this population. The study objective was to evaluate safety and efficacy (including survival) of enzyme replacement with sebelipase alfa in infants with lysosomal acid lipase deficiency. This is an ongoing multicenter, open-label, phase 2/3 study conducted in nine countries. The study enrolled infants with growth failure prior to 6 months of age with rapidly progressive lysosomal acid lipase deficiency; they received once-weekly doses of sebelipase alfa initiated at 0.35 mg/kg with intrapatient dose escalation up to 5 mg/kg. The main outcome of interest is survival to 12 months and survival beyond 24 months of age.