Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized, multicenter, double-blind clinical trial and extension study


Journal Article

© 2019, American College of Medical Genetics and Genomics. Purpose: Outcomes in patients with Fabry disease receiving migalastat during the phase 3 FACETS trial (NCT00925301) were evaluated by phenotype. Methods: Data were evaluated in two subgroups of patients with migalastat-amenable GLA variants: “classic phenotype” (n = 14; males with residual peripheral blood mononuclear cell α-galactosidase A <3% normal and multiorgan system involvement) and “other patients” (n = 36; males not meeting classic phenotype criteria and all females). Endpoints included estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMi), Gastrointestinal Symptoms Rating Scale diarrhea subscale (GSRS-D), renal peritubular capillary (PTC) globotriaosylceramide (GL-3) inclusions, and plasma globotriaosylsphingosine (lyso-Gb 3 ). Results: Baseline measures in the classic phenotype patients suggested a more severe phenotype. At month 24, mean (SD) annualized change in eGFR CKD-EPI with migalastat was −0.3 (3.76) mL/min/1.73 m 2 in the classic phenotype subgroup; changes in LVMi, GSRS-D, and lyso-Gb 3 were −16.7 (18.64) g/m 2 , −0.9 (1.66), and −36.8 (35.78) nmol/L, respectively. At month 6, mean PTC GL-3 inclusions decreased with migalastat (−0.8) and increased with placebo (0.3); switching from placebo to migalastat, PTC inclusions decreased by −0.7. Numerically smaller changes in these endpoints were observed in the other patients. Conclusion: Migalastat provided clinical benefit to patients with Fabry disease and amenable variants, regardless of disease severity.

Full Text

Duke Authors

Cited Authors

  • Germain, DP; Nicholls, K; Giugliani, R; Bichet, DG; Hughes, DA; Barisoni, LM; Colvin, RB; Jennette, JC; Skuban, N; Castelli, JP; Benjamin, E; Barth, JA; Viereck, C

Published Date

  • January 1, 2019

Published In

Electronic International Standard Serial Number (EISSN)

  • 1530-0366

International Standard Serial Number (ISSN)

  • 1098-3600

Digital Object Identifier (DOI)

  • 10.1038/s41436-019-0451-z

Citation Source

  • Scopus