Migalastat improves diarrhea in patients with Fabry disease: Clinical-biomarker correlations from the phase 3 FACETS trial

Raphael Schiffmann, Daniel G. Bichet, Ana Jovanovic, Derralynn A. Hughes, Roberto Giugliani, Ulla Feldt-Rasmussen, Suma Shankar, Laura Barisoni, Robert B. Colvin, J. Charles Jennette, Fred Holdbrook, Andrew Mulberg, Jeffrey P. Castelli, Nina Skuban, Jay A. Barth, Kathleen Nicholls

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Background: Fabry disease is frequently characterized by gastrointestinal symptoms, including diarrhea. Migalastat is an orally-administered small molecule approved to treat the symptoms of Fabry disease in patients with amenable mutations. Methods: We evaluated minimal clinically important differences (MCID) in diarrhea based on the corresponding domain of the patient-reported Gastrointestinal Symptom Rating Scale (GSRS) in patients with Fabry disease and amenable mutations (N = 50) treated with migalastat 150 mg every other day or placebo during the phase 3 FACETS trial (NCT00925301). Results: After 6 months, significantly more patients receiving migalastat versus placebo experienced improvement in diarrhea based on a MCID of 0.33 (43% vs 11%; p =.02), including the subset with baseline diarrhea (71% vs 20%; p =.02). A decline in kidney peritubular capillary globotriaosylceramide inclusions correlated with diarrhea improvement; patients with a reduction > 0.1 were 5.6 times more likely to have an improvement in diarrhea than those without (p =.031). Conclusions: Migalastat was associated with a clinically meaningful improvement in diarrhea in patients with Fabry disease and amenable mutations. Reductions in kidney globotriaosylceramide may be a useful surrogate endpoint to predict clinical benefit with migalastat in patients with Fabry disease. Trial registration: NCT00925301; June 19, 2009.

Original languageEnglish (US)
Article number68
JournalOrphanet Journal of Rare Diseases
Issue number1
StatePublished - Apr 27 2018


  • Amenable mutation
  • Diarrhea
  • Fabry disease
  • Gastrointestinal
  • Globotriaosylceramide
  • GSRS
  • Lyso-Gb
  • Migalastat
  • Pharmacological chaperone

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)


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