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

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  • Holdbrook, Fred
    • Other Affiliation: Amicus Therapeutics, Inc., Cranbury, NJ, USA
  • Jennette, Charles
    • Affiliation: School of Medicine
  • Bichet, Daniel G
    • Other Affiliation: Hôpital du Sacré-Coeur, University of Montreal, Montreal, Quebec, Canada
  • Shankar, Suma P
    • Other Affiliation: Emory University School of Medicine, Atlanta, GA, USA; Present Address: UC Davis MIND Institute, Sacramento, CA, USA
  • Colvin, Robert B
    • Other Affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  • Castelli, Jeffrey P
    • Other Affiliation: Amicus Therapeutics, Inc., Cranbury, NJ, USA
  • Schiffmann, Raphael
    • Other Affiliation: Baylor Scott & White Research Institute, Dallas, TX, USA; Institute of Metabolic Disease, 3812 Elm Street, Dallas, TX 75226, USA
  • Nicholls, Kathleen
    • Other Affiliation: Department of Nephrology, Royal Melbourne Hospital, Parkville, VIC, Australia
  • Skuban, Nina
    • Other Affiliation: Amicus Therapeutics, Inc., Cranbury, NJ, USA
  • Jovanovic, Ana
    • Other Affiliation: Salford Royal Foundation Trust, Manchester, Greater Manchester, UK
  • Barth, Jay A
    • Other Affiliation: Amicus Therapeutics, Inc., Cranbury, NJ, USA
  • Mulberg, Andrew
    • Other Affiliation: Amicus Therapeutics, Inc., Cranbury, NJ, USA
  • Giugliani, Roberto
    • Other Affiliation: Medical Genetics Service, HCPA/UFRGS, Porto Alegre, Brazil
  • Feldt-Rasmussen, Ulla
    • Other Affiliation: Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • Barisoni, Laura
    • Other Affiliation: Miller School of Medicine, University of Miami, Miami, FL, USA
  • Hughes, Derralynn A
    • Other Affiliation: NHS Foundation Trust, Royal Free Hospital, London, UK
  • Abstract 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.
Date of publication
  • doi:10.1186/s13023-018-0813-7
Resource type
  • Article
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  • In Copyright
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  • The Author(s).
  • English
Bibliographic citation
  • Orphanet Journal of Rare Diseases. 2018 Apr 27;13(1):68
  • BioMed Central

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