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

Dominique P. Germain, Kathy Nicholls, Roberto Giugliani, Daniel G. Bichet, Derralynn A. Hughes, Laura M. Barisoni, Robert B. Colvin, J. Charles Jennette, Nina Skuban, Jeffrey P. Castelli, Elfrida Benjamin, Jay A. Barth, Christopher Viereck

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1987-1997
Number of pages11
JournalGenetics in Medicine
Volume21
Issue number9
DOIs
StatePublished - Sep 1 2019

Keywords

  • Fabry disease
  • classic
  • migalastat
  • pharmacogenetics
  • precision medicine

ASJC Scopus subject areas

  • Genetics(clinical)

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