A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease

Purpose: Although Fabry disease is X linked and considered to affect primarily male hemizygotes, female heterozygotes may experience all the signs and symptoms of this metabolic disorder. This prospective, single-center, open-label, clinical trial was performed to evaluate tire long-term response of female patients with Fabry disease to enzyme replacement therapy. Methods: Symptomatic women (average age = 47 years) enrolled in this 4-year study were treated with agalsidase alfa (Replagal (R), Shire HGT, Inc.) at a dose of 0.2 mg/kg, every other week for 4 years (N = 36). Clinical and biochemical assessments were conducted at 12-month intervals. Results: The Mainz Severity Score Index, a measure of total disease burden, was significantly reduced after 12 months (P < 0.01) of treatment and continuously improved over 4 years. Brief Pain Inventory pain at its worst score was reduced from 4.6 +/- 2.9 at baseline to 3.3 +/- 2.9 after 12 months (P = 0.001) and remained reduced through 4 years. Mean left-ventricular mass decreased from 89.4 +/- 29.3 g/m(2.7) at baseline to 66.5 +/- 29.3 g/m(2.7) after 12 months (P < 0.001) and remained reduced through 4 years. Average kidney function (estimated glomerular filtration rate and proteinuria) remained constant during the study. No safety issues were identified. Conclusions: Long-term agalsidase alfa is effective and was well tolerated in women with Fabry disease. Genet Med 2009:11(6): 441-449.