Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease.
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.
Pastores
Gregory M
GM
Department of Neurology, New York University School of Medicine, 403 East 34th Street, New York, NY 10016, and St. Louis Children's Hospital, MO, USA. gregory.pastores@med.nyu.edu
Boyd
Ellen
E
Crandall
Kerry
K
Whelan
Alison
A
Piersall
Linda
L
Barnett
Natalie
N
D000328:Adult; D000368:Aged; D000795:Fabry Disease / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007527:Isoenzymes / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis; D013997:Time Factors; D014281:Trihexosylceramides / Q000097:blood; D000519:alpha-Galactosidase / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*
D007074:Immunoglobulin G; D007527:Isoenzymes; D011994:Recombinant Proteins; D014281:Trihexosylceramides; C000627036:agalsidase alfa; C018549:globotriaosylceramide; D000519:alpha-Galactosidase