NDT Advance Access originally published online on October 4, 2005
Nephrology Dialysis Transplantation 2006 21(2):345-354; doi:10.1093/ndt/gfi152
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Clinical Nephrology
Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke National Institutes of Health, Bethesda, MD and 1 Transkaryotic Therapies, Inc., Cambridge, MA, USA
Correspondence and offprint requests to: Raphael Schiffmann, MD, National Institutes of Health, Building 10, Room 3D03, 9000 Rockville Pike, Bethesda, MD 20892–1260. Email: rs4e{at}nih.gov
Background. Fabry disease is an X-linked disorder of glycosphingolipid catabolism that is the result of an intracellular deficiency in the lysosomal enzyme 
-galactosidase A (-Gal A). This enzymatic defect results in the accumulation of globotriaosylceramide (Gb3) within cells and causes progressive neurological, cardiovascular and renal dysfunction. Our objective is to describe the safety and renal effects of long-term enzyme replacement therapy.
Methods. This was a single centre, prospective open-label treatment trial in 25 adult male Fabry patients who had completed a 6-month randomized placebo-controlled study and subsequently enrolled in an open-label extension study. Patients were treated every other week with agalsidase alfa (0.2 mg/kg) infused intravenously over 40 min. The main outcome measures were safety, antibody response and renal glomerular filtration rate (GFR).
Results. During the 4–4.5 years of enzyme replacement therapy, all eligible subjects were able to transition to home therapy. Eight patients developed persistent IgG antibodies to agalsidase alfa, but IgE antibodies were not detected in any patient. The development of IgG antibodies appeared not to affect any clinical end points. Estimated GFR remained stable in subgroups of patients with Stage I (GFR >90 ml/min) or Stage II (GFR 60–89 ml/min) chronic kidney disease at baseline. In contrast, in the subgroup of patients with Stage III chronic kidney disease (GFR 30–59 ml/min), the slope of the decline in GFR was reduced compared with comparable historical controls, suggesting that enzyme replacement therapy was slowing the decline of renal function in this susceptible population.
Conclusions. Long-term enzyme replacement therapy with agalsidase alfa is safe and may slow the progressive decline in renal function that was commonly observed in adult males with Fabry disease.
Keywords: chronic renal disease; enzyme replacement therapy; Fabry disease; genetic disease; glomerular filtration rate; renal dysfunction
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