ABSTRACT
BACKGROUND: Fabry disease (FD) is caused by an X-linked deficiency in the activity of alpha-galactosidase A and the resultant accumulation of globotriaosylceramide (Gb3) in multiple tissues. Nearly all classically affected males with FD experience kidney dysfunction, with progression to end-stage renal disease (ESRD) in the third decade of life or shortly thereafter. METHODS: Twenty-two FD patients (20 men and 2 women) receiving dialysis or who had a history of kidney transplantation were treated with agalsidase alfa in an open label setting using the same dosing regimen given to patients without ESRD (0.2 mg/kg every other week). Pharmacokinetics (PK) were determined during and following the initial dose, and safety was evaluated during therapy. Change in plasma Gb3 level was used as a surrogate marker of enzyme activity in vivo. RESULTS: A typical biphasic plasma elimination profile was seen in both dialysis and transplant patients, similar to that observed in 18 non-ESRD FD patients. Calculated PK parameters were similar to the three patient groups. In the male patients, plasma Gb3 level declined by 43% after 6 months (P<0.001). Infusion reactions were experienced by 8 of 21 (38%) patients, but did not result in any infusions being stopped prematurely. Anti-agalsidase alfa IgG antibodies were detected in 15.8% of males and 0% female patients. No anti-agalsidase alfa IgE antibodies were detected. CONCLUSIONS: The same dosing regimen of agalsidase alfa may be safely administered to FD patients with ESRD as given to those without ESRD.