Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting

• Published in: Nephrology, dialysis, transplantation Vol. 21; no. 2; pp. 345 - 354
• Main Authors: Schiffmann, Raphael, Ries, Markus, Timmons, Margaret, Flaherty, John T., Brady, Roscoe O.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.02.2006; Oxford Publishing Limited (England)
• Subjects: Adult; alpha-Galactosidase - administration & dosage; alpha-Galactosidase - pharmacology; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; chronic renal disease; Emergency and intensive care: renal failure. Dialysis management; enzyme replacement therapy; Fabry disease; Fabry Disease - drug therapy; genetic disease; glomerular filtration rate; Glomerular Filtration Rate - drug effects; Home Care Services; Humans; Infusions, Intravenous; Intensive care medicine; Isoenzymes - administration & dosage; Isoenzymes - pharmacology; Male; Medical sciences; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Prospective Studies; renal dysfunction; Renal failure; Safety; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; Time Factors; Kidney disease; Nervous system diseases; Replacement therapy; Urinary system disease; Glomerular filtration; Renal function; enzyme replacement therapy; Enzyme; Hemodialysis; glomerular filtration rate; Fabry disease; Cardiovascular disease; Metabolic diseases; Lipids; renal dysfunction; Enzymopathy; Genetic disease; Vascular disease; Extrarenal dialysis; Renal failure; Agalsidase alfa; Lipoidosis; chronic renal disease
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfi152

Background. Fabry disease is an X-linked disorder of glycosphingolipid catabolism that is the result of an intracellular deficiency in the lysosomal enzyme α-galactosidase A (α-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.