HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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

AbstractOBJECTIVE:
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.
AuthorsJ Edmond Wraith, Anna Tylki-Szymanska, Nathalie Guffon, Y Howard Lien, Michel Tsimaratos, Ashok Vellodi, Dominique P Germain
JournalThe Journal of pediatrics (J Pediatr) Vol. 152 Issue 4 Pg. 563-70, 570.e1 (Apr 2008) ISSN: 1097-6833 [Electronic] United States
PMID18346516 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies
  • Immunoglobulin G
  • Isoenzymes
  • Trihexosylceramides
  • globotriaosylceramide
  • Creatinine
  • alpha-Galactosidase
  • agalsidase beta
Topics
  • Adolescent
  • Antibodies (blood)
  • Capillaries (metabolism)
  • Child
  • Creatinine (blood)
  • Dermis (blood supply, metabolism)
  • Endothelium (metabolism)
  • Fabry Disease (blood, drug therapy, physiopathology)
  • Female
  • Growth
  • Humans
  • Immunoglobulin G (blood)
  • Infusions, Intravenous
  • Isoenzymes (adverse effects, immunology, therapeutic use)
  • Male
  • Nausea
  • Trihexosylceramides (metabolism)
  • alpha-Galactosidase (adverse effects, immunology, therapeutic use)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: