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


METHODS
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.
Wraith
J Edmond
JE
Royal Manchester Children's Hospital, Manchester, United Kingdom.
Tylki-Szymanska
Anna
A
Guffon
Nathalie
N
Lien
Y Howard
YH
Tsimaratos
Michel
M
Vellodi
Ashok
A
Germain
Dominique P
DP
D000293:Adolescent; D000906:Antibodies / Q000097:blood; D002196:Capillaries / Q000378:metabolism; D002648:Child; D003404:Creatinine / Q000097:blood; D020405:Dermis / Q000098:blood supply / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D000795:Fabry Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006128:Growth; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007262:Infusions, Intravenous; D007527:Isoenzymes / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D009325:Nausea; D014281:Trihexosylceramides / Q000378:metabolism*; D000519:alpha-Galactosidase / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
D000906:Antibodies; D007074:Immunoglobulin G; D007527:Isoenzymes; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D003404:Creatinine; D000519:alpha-Galactosidase; C459420:agalsidase beta