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
- PMID: 40215726
- DOI: 10.1016/j.ymgme.2025.109102
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
Abstract
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 safety findings observed. Renal and cardiac measures remained within the normal range for adolescent patients throughout ASPIRE and the OLE with no meaningful changes observed with migalastat treatment. Plasma lyso-Gb3 levels were stable. Pain related to heat or exertion (as measured by FPHPQ) improved with migalastat treatment, and other patient-reported measures of pain, gastrointestinal symptoms, and quality of life remained stable. These data show a benefit of long-term migalastat treatment in this adolescent patient population with amenable GLA variants.
Keywords: Adolescents; Efficacy; Fabry disease; Migalastat; Quality of life; Safety.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest Uma Ramaswami reports research grants from Amicus Therapeutics, Intrabio and Takeda, honoraria for advisory boards from Amicus Therapeutics, Chiesi, Sanofi, and Takeda, and speaker fees from Amicus Therapeutics, Chiesi and Takeda. Esperanza Font-Montgomery has no conflicts of interest to report. Ozlem Goker-Alpan reports being contracted by Amicus Therapeutics as a principal investigator and consulting fees, honoraria, travel support, and grant support for clinical trials from Sanofi and Chiesi. Damara Ortiz reports research grants from 4D Molecular Therapeutics, Allievex, AvroBio, Cyclo Therapeutics, Freeline, Pfizer, Sangamo Therapeutics, Sanofi, Takeda, UniCure, and Zevra, advisory board membership, participation and honoraria for Sanofi, support for travel from Amicus Therapeutics, and participation in a data safety monitoring board for 4D Molecular Therapeutics. Amarilis Sanchez-Valle reports being contracted by Amicus Therapeutics as a principal investigator. Chester B. Whitley reports that Amicus Therapeutics reimbursed their employer, the University of Minnesota, for the cost to implement two patients who were enrolled and evaluated longitudinally in the clinical trial reported in this scientific article. William Wilcox reports research grants to their institution from 4D Molecular Therapeutics, Alexion, Amgen, Amicus Therapeutics, Astellas, BioMarin, Chiesi, Cyclo Therapeutics, Denali, Protalix, Sangamo Therapeutics, Sanofi-Genzyme, and Takeda, receiving consulting fees from UniQure and Spark Therapeutics/Roche, and participation in advisory boards for Sanofi-Genzyme and Chiesi. On behalf of their spouse, they report stocks and other financial interests in Prevention Genetics. Hai Jiang reports employment with, and stocks in, Amicus Therapeutics. Lee Ann Lawson reports unpaid membership of the Board of Directors for the International Association of Clinical Research Nurses, and employment with, and stocks in, Amicus Therapeutics. Jennie Vosk reports employment with, and stocks in, Amicus Therapeutics. Haichen Yang reports employment with, and stocks in, Amicus Therapeutics. Robert J. Hopkin reports research grants to their institution from Amicus Therapeutics, Chiesi, Sangamo Therapeutics, Sanofi, Spur, and Takeda, consulting fees from Amicus Therapeutics, Chiesi, Freeline, Hanmi, Octant, Sangamo Therapeutics, and Sanofi, speaker bureaus from Sanofi, speaker invitations from Amicus Therapeutics, Chiesi and Fabry Support & Information Group, support for travel from Amicus Therapeutics, Chiesi, Fabry Support & Information Group, National Fabry Disease Foundation, Sangamo Therapeutics, and Sanofi, participation in advisory boards for Acadia Pharmaceuticals and Denali, and leadership or fiduciary roles in the 1p36 Support and Information group, Amicus Therapeutics FollowME Registry Board, Fabry Registry Board of Medical Advisors, Fabry Support & Information Group, National Fabry Disease Foundation Board of Advisors, and the Think Genetic advisory board.
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