Safety and effectiveness of enzyme replacement therapy with agalsidase alfa in patients with Fabry disease: Post-marketing surveillance in Japan.

Fabry disease is a rare X-linked inherited multisystem disorder resulting from deficiency of the lysosomal enzyme alpha-galactosidase A. Currently, specific therapies, including enzyme replacement therapies, are available for Fabry disease, but clinical trials provide limited information on long-term safety and effectiveness. Agalsidase alfa was approved in Japan in 2006. The post-marketing surveillance study of all patients receiving agalsidase alfa to evaluate its long-term safety and effectiveness as a mandatory condition for its approval had been conducted for 8 years (from February 2007 to March 2015). A total of 493 patients were included in this analysis of safety and effectiveness. The overall mean follow-up period was 3.5 years (range, 0.0-7.9 years). The percentage of patients with adverse drug reactions was 24.5% (121/493) and 12.6% had infusion-related reactions (62/493). In the 256 patients without prior enzyme replacement therapy whose IgG antibody data were available, 17 were IgG antibody positive (6.6%). However, the chronological correlation between seroconversion and the incidence of infusion-related reactions was not clear. The mean brief pain inventory score of the worst pain decreased in patients with moderate and severe pain at baseline. Plasma Gb and urine sediment Gb in males with classical Fabry disease without prior enzyme replacement therapy significantly decreased. The mean yearly changes in eGFR (mL/min/1.73 m) ranged from -2.88 to +1.00 in males with classical Fabry disease, from -2.04 to -0.95 in males with non-typical variant and from -2.64 to -1.02 in females. The lower eGFR or the more proteinuria at baseline, the faster the decrease in eGFR of the patients was observed. There was no substantial difference in cardiac parameters (left ventricular mass index, E/A wave ratio, ejection fraction, and QRS duration). In conclusion, agalsidase alfa, 0.2 mg/kg every other week, was well tolerated and controlled the progression of symptoms (especially renal and cardiac) of Fabry disease in adults. Enzyme replacement therapy should be started in Japanese patients before cardiac and/or renal symptoms of Fabry disease develop.