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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

PURPOSE: Outcomes in patients with Fabry disease receiving migalastat during the phase 3 FACETS trial (NCT00925301) were evaluated by phenotype. METHODS: Data were evaluated in two subgroups of patients with migalastat-amenable GLA variants: “classic phenotype” (n = 14; males with residual periphera...

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Autores principales: Germain, Dominique P., Nicholls, Kathy, Giugliani, Roberto, Bichet, Daniel G., Hughes, Derralynn A., Barisoni, Laura M., Colvin, Robert B., Jennette, J. Charles, Skuban, Nina, Castelli, Jeffrey P., Benjamin, Elfrida, Barth, Jay A., Viereck, Christopher
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752321/
https://www.ncbi.nlm.nih.gov/pubmed/30723321
http://dx.doi.org/10.1038/s41436-019-0451-z
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author Germain, Dominique P.
Nicholls, Kathy
Giugliani, Roberto
Bichet, Daniel G.
Hughes, Derralynn A.
Barisoni, Laura M.
Colvin, Robert B.
Jennette, J. Charles
Skuban, Nina
Castelli, Jeffrey P.
Benjamin, Elfrida
Barth, Jay A.
Viereck, Christopher
author_facet Germain, Dominique P.
Nicholls, Kathy
Giugliani, Roberto
Bichet, Daniel G.
Hughes, Derralynn A.
Barisoni, Laura M.
Colvin, Robert B.
Jennette, J. Charles
Skuban, Nina
Castelli, Jeffrey P.
Benjamin, Elfrida
Barth, Jay A.
Viereck, Christopher
author_sort Germain, Dominique P.
collection PubMed
description PURPOSE: Outcomes in patients with Fabry disease receiving migalastat during the phase 3 FACETS trial (NCT00925301) were evaluated by phenotype. METHODS: Data 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-Gb(3)). RESULTS: Baseline measures in the classic phenotype patients suggested a more severe phenotype. At month 24, mean (SD) annualized change in eGFR(CKD-EPI) with migalastat was −0.3 (3.76) mL/min/1.73 m(2) in the classic phenotype subgroup; changes in LVMi, GSRS-D, and lyso-Gb(3) were −16.7 (18.64) g/m(2), −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. CONCLUSION: Migalastat provided clinical benefit to patients with Fabry disease and amenable variants, regardless of disease severity.
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spelling pubmed-67523212019-09-23 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 Germain, Dominique P. Nicholls, Kathy Giugliani, Roberto Bichet, Daniel G. Hughes, Derralynn A. Barisoni, Laura M. Colvin, Robert B. Jennette, J. Charles Skuban, Nina Castelli, Jeffrey P. Benjamin, Elfrida Barth, Jay A. Viereck, Christopher Genet Med Article PURPOSE: Outcomes in patients with Fabry disease receiving migalastat during the phase 3 FACETS trial (NCT00925301) were evaluated by phenotype. METHODS: Data 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-Gb(3)). RESULTS: Baseline measures in the classic phenotype patients suggested a more severe phenotype. At month 24, mean (SD) annualized change in eGFR(CKD-EPI) with migalastat was −0.3 (3.76) mL/min/1.73 m(2) in the classic phenotype subgroup; changes in LVMi, GSRS-D, and lyso-Gb(3) were −16.7 (18.64) g/m(2), −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. CONCLUSION: Migalastat provided clinical benefit to patients with Fabry disease and amenable variants, regardless of disease severity. Nature Publishing Group US 2019-02-06 2019 /pmc/articles/PMC6752321/ /pubmed/30723321 http://dx.doi.org/10.1038/s41436-019-0451-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, and provide a link to the Creative Commons license. You do not have permission under this license to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Article
Germain, Dominique P.
Nicholls, Kathy
Giugliani, Roberto
Bichet, Daniel G.
Hughes, Derralynn A.
Barisoni, Laura M.
Colvin, Robert B.
Jennette, J. Charles
Skuban, Nina
Castelli, Jeffrey P.
Benjamin, Elfrida
Barth, Jay A.
Viereck, Christopher
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752321/
https://www.ncbi.nlm.nih.gov/pubmed/30723321
http://dx.doi.org/10.1038/s41436-019-0451-z
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