Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized,multicenter, double-blind clinical trial and extension study |
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| Institution: | 1. Division of Medical Genetics and Inserm U1179, University of Versailles, Paris-Saclay University, Montigny, France;;2. Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia;;3. Medical Genetics Service, HCPA, and Department of Genetics, UFRGS, Porto Alegre, Brazil;;4. Department of Nephrology, Hôpital du Sacré-Coeur, University of Montreal, Montreal, QC, Canada;;5. Royal Free NHS Foundation Trust and University College London, London, UK;;6. Department of Pathology, University of Miami, Miller School of Medicine, Miami, FL, USA;;7. Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA;;8. School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;;9. Amicus Therapeutics, Inc, Cranbury, NJ, USA.;1. Division of Medical Genetics and Inserm U1179, University of Versailles, Paris-Saclay University, Montigny, France;;2. Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia;;3. Medical Genetics Service, HCPA, and Department of Genetics, UFRGS, Porto Alegre, Brazil;;4. Department of Nephrology, Hôpital du Sacré-Coeur, University of Montreal, Montreal, QC, Canada;;5. Royal Free NHS Foundation Trust and University College London, London, UK;;6. Department of Pathology, University of Miami, Miller School of Medicine, Miami, FL, USA;;7. Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA;;8. School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;;9. Amicus Therapeutics, Inc, Cranbury, NJ, USA. |
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| Abstract: | PurposeOutcomes in patients with Fabry disease receiving migalastat during the phase 3 FACETS trial (NCT00925301) were evaluated by phenotype.MethodsData were evaluated in two subgroups of patients with migalastat-amenable GLA variants: “classic phenotype” (n = 14; males with residual peripheral blood mononuclear cell α-galactosidase A <3% normal and multiorgan system involvement) and “other patients” (n = 36; males not meeting classic phenotype criteria and all females). Endpoints included estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMi), Gastrointestinal Symptoms Rating Scale diarrhea subscale (GSRS-D), renal peritubular capillary (PTC) globotriaosylceramide (GL-3) inclusions, and plasma globotriaosylsphingosine (lyso-Gb3).ResultsBaseline measures in the classic phenotype patients suggested a more severe phenotype. At month 24, mean (SD) annualized change in eGFRCKD-EPI with migalastat was ?0.3 (3.76) mL/min/1.73 m2 in the classic phenotype subgroup; changes in LVMi, GSRS-D, and lyso-Gb3 were ?16.7 (18.64) g/m2, ?0.9 (1.66), and ?36.8 (35.78) nmol/L, respectively. At month 6, mean PTC GL-3 inclusions decreased with migalastat (?0.8) and increased with placebo (0.3); switching from placebo to migalastat, PTC inclusions decreased by ?0.7. Numerically smaller changes in these endpoints were observed in the other patients.ConclusionMigalastat provided clinical benefit to patients with Fabry disease and amenable variants, regardless of disease severity. |
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