Safety and efficacy of migalastat in adolescent patients with Fabry disease: Results from ASPIRE, a phase 3b, open-label, single-arm, 12-month clinical trial, and its open-label extension

作者：Uma Ramaswami, Esperanza Font–Montgomery, Özlem Göker-Alpan, Damara Ortiz, Amarilis Sanchez‐Valle, Chester B. Whitley, William R. Wilcox, Hai Jiang, Lee Ann Lawson, Jennie Vosk, Haichen Yang, Robert J. Hopkin · 发表于：Molecular Genetics and Metabolism · 年份：2025 · DOI：10.1016/j.ymgme.2025.109102 · 被引用次数：5 · 研究领域：Lysosomal Storage Disorders Research、Glycogen Storage Diseases and Myoclonus、Carbohydrate Chemistry and Synthesis

Fabry disease (FD) is a progressive, multisystemic, X-linked lysosomal disorder caused by reduced or absent α-galactosidase A activity due to galactosidase alpha (GLA) gene variants. Although clinical manifestations of FD often appear in childhood, approved treatments for the management of FD in children and adolescents are limited. ASPIRE (NCT03500094) was a phase 3b, two-stage, open-label, multicenter study evaluating the safety, pharmacokinetics, and efficacy of migalastat in adolescents 12 to <18 years, ≥ 45 kg with FD and amenable GLA variants. Long-term outcomes were evaluated in the ongoing open-label extension (OLE) study (NCT04049760). Pharmacokinetic results (a primary objective of ASPIRE) were reported previously. Here, we report safety, efficacy, pharmacodynamic, and patient-reported outcome measures in adolescents treated with migalastat for up to 48 months across ASPIRE and the subsequent OLE. Outcome measures included treatment-emergent adverse events, estimated glomerular filtration rate, left ventricular mass index, plasma globotriaosylsphingosine (lyso-Gb3) levels, the Fabry-specific Pediatric Health and Pain Questionnaire (FPHPQ), and the Pediatric Quality of Life Inventory™. Overall, 21 patients (52.4 % female) received at least one dose of migalastat in ASPIRE, 11 of whom were enzyme replacement therapy experienced. Mean age at study entry was 14.7 years. Treatment with migalastat was well tolerated in this adolescent population with no new or unexpected ...