Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease

J Pediatr. 2008 Apr;152(4):563-70, 570.e1. doi: 10.1016/j.jpeds.2007.09.007. Epub 2007 Dec 3.


Objective: To evaluate the safety and explore the efficacy of enzyme replacement therapy with agalsidase beta (recombinant human alpha-galactosidase A; Fabrazyme [Genzyme Corporation, Cambridge, MA]) in pediatric patients with Fabry disease, a genetic disorder in which deficient endogenous enzyme causes pathogenic tissue accumulation of globotriaosylceramide (GL-3).

Study design: Fourteen male and 2 female patients, 8 to 16 years old, were treated in this open-label study. A 12-week observation period to collect baseline data preceded the 48-week treatment period when agalsidase beta (1 mg/kg) was infused intravenously every 2 weeks. No primary efficacy end point was specified.

Results: Before treatment, results of skin biopsies from 12 male patients showed moderate or severe GL-3 accumulation in superficial dermal capillary endothelial cells; with treatment, these cells were completely cleared of GL-3 in week-24 biopsies from all 12 male patients and in all available week-48 biopsies. With treatment, reports of gastrointestinal symptoms declined steadily. Patient diaries documented significant reductions in school absences due to sickness. Agalsidase beta was generally well tolerated; most treatment-related adverse events were mild or moderate infusion-associated reactions involving rigors, fever, or rhinitis.

Conclusions: Agalsidase beta safely and effectively reduced the GL-3 accumulation in dermal endothelium already evident in children with Fabry disease. Early intervention may prevent irreversible end-organ damage from chronic GL-3 deposition.

Trial registration: NCT00074958.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies / blood
  • Capillaries / metabolism
  • Child
  • Creatinine / blood
  • Dermis / blood supply
  • Dermis / metabolism*
  • Endothelium / metabolism
  • Fabry Disease / blood
  • Fabry Disease / drug therapy*
  • Fabry Disease / physiopathology
  • Female
  • Growth
  • Humans
  • Immunoglobulin G / blood
  • Infusions, Intravenous
  • Isoenzymes / adverse effects
  • Isoenzymes / immunology
  • Isoenzymes / therapeutic use*
  • Male
  • Nausea
  • Trihexosylceramides / metabolism*
  • alpha-Galactosidase / adverse effects
  • alpha-Galactosidase / immunology
  • alpha-Galactosidase / therapeutic use*


  • Antibodies
  • Immunoglobulin G
  • Isoenzymes
  • Trihexosylceramides
  • globotriaosylceramide
  • Creatinine
  • alpha-Galactosidase
  • agalsidase beta

Associated data