Four-year prospective clinical trial of agalsidase alfa in children with Fabry disease.
OBJECTIVE
To investigate a 4-year prospective clinical trial of agalsidase alfa in children with Fabry disease, an X-linked metabolic disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A.


METHODS
Seventeen (16 boys, 1 girl; age range, 7.3 to 18.4 years) of the 24 children who completed a 6-month, open-label agalsidase alfa study enrolled in a 3.5-year extension study that investigated the safety and potential efficacy of long-term treatment. All 17 patients completed the initial 6-month study, and 10 patients (9 boys) completed the extension study.


RESULTS
Agalsidase alfa was well tolerated. In treated boys, there were sustained, statistically-significant improvements in the clinical features of Fabry disease, including reduced plasma globotriaosylceramide levels, reduced pain severity assessed by the Brief Pain Index, and improved heart rate variability. Mean urine globotriaosylceramide levels were reduced to normal range (P < .05 compared with baseline during 1.5 to 4 years). Kidney function and left ventricular mass indexed to height remained stable throughout.


CONCLUSIONS
This clinical trial demonstrates that treatment with agalsidase alfa was well tolerated and associated with improvement of Fabry disease-related features.
Schiffmann
Raphael
R
Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX 75226, USA. Raphael.Schiffmann@baylorhealth.edu
Martin
Rick A
RA
Reimschisel
Tyler
T
Johnson
Karen
K
Castaneda
Victoria
V
Lien
Y Howard
YH
Pastores
Gregory M
GM
Kampmann
Christoph
C
Ries
Markus
M
Clarke
Joe T R
JT
D000293:Adolescent; D049628:Body Size; D002648:Child; D000795:Fabry Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000009:adverse effects / Q000627:therapeutic use; D007668:Kidney / Q000503:physiopathology; D008297:Male; D010147:Pain Measurement; D011994:Recombinant Proteins; D013542:Sweat / Q000502:physiology; D014281:Trihexosylceramides / Q000097:blood / Q000652:urine; D016277:Ventricular Function, Left; D000519:alpha-Galactosidase / Q000009:adverse effects / Q000627:therapeutic use*
D007527:Isoenzymes; D011994:Recombinant Proteins; D014281:Trihexosylceramides; C000627036:agalsidase alfa; C018549:globotriaosylceramide; D000519:alpha-Galactosidase