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Long-term safety and efficacy of enzyme replacement therapy for Fabry disease.
Am J Hum Genet. 2004 Jul; 75(1):65-74.AJ

Abstract

Elsewhere, we reported the safety and efficacy results of a multicenter phase 3 trial of recombinant human alpha -galactosidase A (rh-alpha GalA) replacement in patients with Fabry disease. All 58 patients who were enrolled in the 20-wk phase 3 double-blind, randomized, and placebo-controlled study received subsequently 1 mg/kg of rh-alpha GalA (agalsidase beta, Fabrazyme, Genzyme Corporation) biweekly in an ongoing open-label extension study. Evidence of long-term efficacy, even in patients who developed IgG antibodies against rh- alpha GalA, included the continuously normal mean plasma globotriaosylceramide (GL-3) levels during 30 mo of the extension study and the sustained capillary endothelial GL-3 clearance in 98% (39/40) of patients who had a skin biopsy taken after treatment for 30 mo (original placebo group) or 36 mo (original enzyme-treated group). The mean serum creatinine level and estimated glomerular filtration rate also remained stable after 30-36 mo of treatment. Infusion-associated reactions decreased over time, as did anti-rh- alpha GalA IgG antibody titers. Among seroconverted patients, after 30-36 mo of treatment, seven patients tolerized (no detectable IgG antibody), and 59% had > or =4-fold reductions in antibody titers. As of 30 mo into the extension trial, three patients were withdrawn from the study because of positive serum IgE or skin tests; however, all have been rechallenged successfully at the time of this report. Thus, enzyme replacement therapy for 30-36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels, sustained endothelial GL-3 clearance, stable kidney function, and a favorable safety profile.

Authors+Show Affiliations

Cedars-Sinai Burns and Allen Research Institute and UCLA School of Medicine, Los Angeles, CA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Clinical Trial, Phase III
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15154115

Citation

Wilcox, William R., et al. "Long-term Safety and Efficacy of Enzyme Replacement Therapy for Fabry Disease." American Journal of Human Genetics, vol. 75, no. 1, 2004, pp. 65-74.
Wilcox WR, Banikazemi M, Guffon N, et al. Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet. 2004;75(1):65-74.
Wilcox, W. R., Banikazemi, M., Guffon, N., Waldek, S., Lee, P., Linthorst, G. E., Desnick, R. J., & Germain, D. P. (2004). Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. American Journal of Human Genetics, 75(1), 65-74.
Wilcox WR, et al. Long-term Safety and Efficacy of Enzyme Replacement Therapy for Fabry Disease. Am J Hum Genet. 2004;75(1):65-74. PubMed PMID: 15154115.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. AU - Wilcox,William R, AU - Banikazemi,Maryam, AU - Guffon,Nathalie, AU - Waldek,Stephen, AU - Lee,Philip, AU - Linthorst,Gabor E, AU - Desnick,Robert J, AU - Germain,Dominique P, AU - ,, Y1 - 2004/05/20/ PY - 2004/02/11/received PY - 2004/05/04/accepted PY - 2004/5/22/pubmed PY - 2004/7/21/medline PY - 2004/5/22/entrez SP - 65 EP - 74 JF - American journal of human genetics JO - Am J Hum Genet VL - 75 IS - 1 N2 - Elsewhere, we reported the safety and efficacy results of a multicenter phase 3 trial of recombinant human alpha -galactosidase A (rh-alpha GalA) replacement in patients with Fabry disease. All 58 patients who were enrolled in the 20-wk phase 3 double-blind, randomized, and placebo-controlled study received subsequently 1 mg/kg of rh-alpha GalA (agalsidase beta, Fabrazyme, Genzyme Corporation) biweekly in an ongoing open-label extension study. Evidence of long-term efficacy, even in patients who developed IgG antibodies against rh- alpha GalA, included the continuously normal mean plasma globotriaosylceramide (GL-3) levels during 30 mo of the extension study and the sustained capillary endothelial GL-3 clearance in 98% (39/40) of patients who had a skin biopsy taken after treatment for 30 mo (original placebo group) or 36 mo (original enzyme-treated group). The mean serum creatinine level and estimated glomerular filtration rate also remained stable after 30-36 mo of treatment. Infusion-associated reactions decreased over time, as did anti-rh- alpha GalA IgG antibody titers. Among seroconverted patients, after 30-36 mo of treatment, seven patients tolerized (no detectable IgG antibody), and 59% had > or =4-fold reductions in antibody titers. As of 30 mo into the extension trial, three patients were withdrawn from the study because of positive serum IgE or skin tests; however, all have been rechallenged successfully at the time of this report. Thus, enzyme replacement therapy for 30-36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels, sustained endothelial GL-3 clearance, stable kidney function, and a favorable safety profile. SN - 0002-9297 UR - https://www.unboundmedicine.com/medline/citation/15154115/Long_term_safety_and_efficacy_of_enzyme_replacement_therapy_for_Fabry_disease_ DB - PRIME DP - Unbound Medicine ER -