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

• Autor(a) principal: Germain, Dominique P.
• Data de Publicação: 2019
• Outros Autores: Nicholls, Kathy, Giugliani, Roberto, Bichet, Daniel G., Hughes, Derralynn A., Barisoni, Laura, Colvin, Robert B., Jennette, J. Charles, Skuban, Nina, Castelli, Jeffrey P., Benjamin, Elfrida R., Barth, Jay, Viereck, Christopher
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/200932
• topic: Fenótipo; Doença de Fabry; Estudo clínico; Tratamento farmacológico; Ensaio clínico controlado aleatório; Estudo multicêntrico; Método duplo-cego; Homens; Fabry disease; Migalastat; Classic; Pharmacogenetics; Precision medicine

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 αgalactosidase 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). Results: Baseline 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. Conclusion: Migalastat provided clinical benefit to patients with Fabry disease and amenable variants, regardless of disease severity.