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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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.
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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Author working as a consultant under the contract of Pharmaland Consulting Group.
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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). https://doi.org/10.1038/s41436-020-00968-z
- clinical monitoring
- Fabry disease