Assessment of plasma lyso-Gb3 for clinical monitoring of treatment response in migalastat-treated patients with Fabry disease



To assess the utility of globotriaosylsphingosine (lyso-Gb3) for clinical monitoring of treatment response in patients with Fabry disease receiving migalastat.


A post hoc analysis evaluated data from 97 treatment-naive and enzyme replacement therapy (ERT)–experienced patients with migalastat-amenable GLA variants from FACETS (NCT00925301) and ATTRACT (NCT01218659) and subsequent open-label extension studies. The relationship between plasma lyso-Gb3 and measures of Fabry disease progression (left ventricular mass index [LVMi], estimated glomerular filtration rate [eGFR], and pain) and the relationship between lyso-Gb3 and incidence of Fabry-associated clinical events (FACEs) were assessed in both groups. The relationship between changes in lyso-Gb3 and kidney interstitial capillary (KIC) globotriaosylceramide (Gb3) inclusions was assessed in treatment-naive patients.


No significant correlations were identified between changes in lyso-Gb3 and changes in LVMi, eGFR, or pain. Neither baseline lyso-Gb3 levels nor the rate of change in lyso-Gb3 levels during treatment predicted FACE occurrences in all patients or those receiving migalastat for ≥24 months. Changes in lyso-Gb3 correlated with changes in KIC Gb3 inclusions in treatment-naive patients.


Although used as a pharmacodynamic biomarker in research and clinical studies, plasma lyso-Gb3 may not be a suitable biomarker for monitoring treatment response in migalastat-treated patients.

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Fig. 1: Lack of correlation between changes in plasma lyso-Gb3 and changes in LVMi, eGFR, and pain at selected timepoints of migalastat treatment.


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We thank Simon Heales, David Kasper, and Sarah Young for their contributions to the development of this study. Third-party medical writing assistance was provided by Lei Bai and Stephanie Agbu (ApotheCom, Yardley, PA)


This study was funded by Amicus Therapeutics, Inc.

Author information




DGB, ABM, and NS participated in study design; DGB, ABM, NS, and EK analyzed the data; and DGB, CAB, HM, ABM, NS, and EK interpreted the data. JMA drafted the article. All authors critically revised the manuscript, gave final approval of the submitted version, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Raphael Schiffmann MD.

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D.G.B. has served as a consultant and speaker for, and received research funding and honoraria from, Amicus Therapeutics, Inc. and Sanofi Genzyme. J.M.A. has served as a consultant for Azafaros and as a speaker for Amicus Therapeutics, Inc. and Sanofi Genzyme. C.A.-B. has served as a consultant and speaker for Amicus Therapeutics, Inc. and Sanofi Genzyme; has served as a collaborator for 4D Molecular Therapeutics, Avrobio, and Protalix; has received research grants and honoraria as an investigator for BioMarin Pharmaceutical Inc., Shire/Takeda, and University Health Network; and has received research equipment and supplies from Waters Corporation. H.M. has received research support from Amicus Therapeutics, Inc. and Idorsia; and has received speaker fees from Amicus Therapeutics, Inc. and Sanofi K.K. A.T.B. has received honoraria from and served as a consultant and investigator for Amicus Therapeutics, Inc., Protalix/Pfizer, Sanofi Genzyme, and Shire/Takeda. N.S. is an employee of and holds stock in Amicus Therapeutics, Inc. E.K. is a paid consultant for Amicus Therapeutics, Inc. R.S. has served as a consultant for Chiesi Farmaceutici and Amicus Therapeutics, Inc., and has served as an investigator for Idorsia, Protalix, and Sanofi Genzyme.

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Bichet, D.G., Aerts, J.M., Auray-Blais, C. et al. Assessment of plasma lyso-Gb3 for clinical monitoring of treatment response in migalastat-treated patients with Fabry disease. Genet Med (2020).

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Key words

  • biomarker
  • clinical monitoring
  • Fabry disease
  • lyso-Gb3
  • migalastat