Safety and pharmacodynamic effects of a pharmacological chaperone on α-galactosidase A activity and globotriaosylceramide clearance in Fabry disease: report from two phase 2 clinical studies

Table 7 Summary of α-Gal A increase and GL-3 reduction for each patient and combined score according to HEK-293 response status

Patient	2-0103	2-0104	2-0202	3-0301	3RF01	3RF03	2-0102	3-0302	3-0303
Mutation	p.P259R	p.P259R	p.R301Q	p.F295C	p.N215S	p.P205T	p.L415P	p.C94S	p.R112C
HEK-293	R	R	R	R	R	R	NR	NR	NR
α-Gal A PBMC (at least +50%)	+	+	+	+	+	+	-	-	+
α-Gal A kidney (at least +50%)	+	+	+	+	+	+	-	-	-
α-Gal A skin (at least +50%)	+	+	+	+	+	+	+	+	+
u-GL3	+ (−60%)	+ (−75%)	+ (−38%)	-	+ (−20%)	+ (−52%)	-	-	-
GL-3 skin LC/MS	+ (−31%)	+ (−11%)	-	-	-	+ (−57%)	-	-	-
GL-3 kidney LC/MS	+ (−41%)	+ (−6%)	+ (−21%)	-	-	+ (−36%)	+ (−22%)	-	-
GL-3 kidney Inclusion (−50%)	+	+	-	+	+	^a	-	-	-
Combined score	+	+	+	+	+	+	-	-	-

HEK-293 = transfection assay in Human Embryonic Kidney-293 cells, R = responsive mutation, NR = non-responsive mutation, α-Gal A = alpha galactosidase A, PBMCs = Peripheral Blood Mononuclear Cells, GL-3 = globotriaosylceramide, u = urine, s = skin, k = kidney, LC/MS = Liquid Chromatography - Mass Spectrometry.
^a baseline biopsy not evaluable.

ISSN: 1750-1172