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

Genet Med. 2019 Sep;21(9):1987-1997. doi: 10.1038/s41436-019-0451-z. Epub 2019 Feb 6.


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-Gb3).

Results: Baseline measures in the classic phenotype patients suggested a more severe phenotype. At month 24, mean (SD) annualized change in eGFRCKD-EPI with migalastat was -0.3 (3.76) mL/min/1.73 m2 in the classic phenotype subgroup; changes in LVMi, GSRS-D, and lyso-Gb3 were -16.7 (18.64) g/m2, -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.

Keywords: Fabry disease; classic; migalastat; pharmacogenetics; precision medicine.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / administration & dosage
  • 1-Deoxynojirimycin / adverse effects
  • 1-Deoxynojirimycin / analogs & derivatives*
  • Adolescent
  • Adult
  • Double-Blind Method
  • Fabry Disease / drug therapy*
  • Fabry Disease / genetics
  • Fabry Disease / pathology
  • Female
  • Genetic Variation / genetics
  • Glomerular Filtration Rate / genetics
  • Humans
  • Kidney / pathology
  • Leukocytes, Mononuclear
  • Male
  • Middle Aged
  • Mutation
  • Pharmacogenetics
  • Precision Medicine*
  • Young Adult
  • alpha-Galactosidase / genetics*


  • 1-Deoxynojirimycin
  • migalastat
  • GLA protein, human
  • alpha-Galactosidase

Associated data

  • ClinicalTrials.gov/NCT00925301