Assessment of plasma lyso-Gb3 for clinical monitoring of treatment response in migalastat-treated patients with Fabry disease
Daniel G. Bichet, Johannes M. F. G. Aerts, Christiane Auray‐Blais, Hiroki Maruyama, Atul Mehta, Nina Skuban, Eva Krusinska, Raphael Schiffmann
Abstract
PurposeTo assess the utility of globotriaosylsphingosine (lyso-Gb3) for clinical monitoring of treatment response in patients with Fabry disease receiving migalastat.MethodsA 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.ResultsNo 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.ConclusionsAlthough 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.