Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease

Nephrol Dial Transplant. 2007 Jul;22(7):1920-5. doi: 10.1093/ndt/gfm096. Epub 2007 Mar 29.


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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Fabry Disease / blood
  • Fabry Disease / complications*
  • Fabry Disease / drug therapy*
  • Fabry Disease / metabolism
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Isoenzymes / adverse effects
  • Isoenzymes / immunology
  • Isoenzymes / pharmacokinetics
  • Isoenzymes / therapeutic use
  • Kidney Failure, Chronic / etiology*
  • Kidney Failure, Chronic / therapy
  • Kidney Transplantation
  • Male
  • Medical Records
  • Middle Aged
  • Recombinant Proteins
  • Renal Dialysis
  • Time Factors
  • Trihexosylceramides / blood
  • alpha-Galactosidase / adverse effects
  • alpha-Galactosidase / immunology
  • alpha-Galactosidase / pharmacokinetics
  • alpha-Galactosidase / therapeutic use*


  • Immunoglobulin G
  • Isoenzymes
  • Recombinant Proteins
  • Trihexosylceramides
  • agalsidase alfa
  • globotriaosylceramide
  • alpha-Galactosidase