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

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.