Abstract Introduction Fabry disease (FD) is a progressive lysosomal disorder caused by variants in the GLA gene. It is characterised by multisystemic dysfunction, predominantly affecting the renal, cardiac and nervous systems. Treatment options include enzyme replacement therapy (ERT) or migalastat, an oral chaperone therapy for patients (pts) with amenable GLA variants. Purpose The followME Fabry Pathfinders registry is an ongoing, multinational, observational, patient-focused registry that evaluates the long-term safety, efficacy and patient-reported outcomes for pts with FD who are untreated or undergoing treatment with ERT or migalastat in the real world. Here, we present data from pts treated with migalastat in Spain and Portugal. Methods Pts ≥12 years of age with a confirmed FD diagnosis and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² were enrolled in the followME registry in one of three groups: pts with migalastat-amenable GLA variants receiving migalastat; pts with any GLA variant receiving ERT; or untreated pts with migalastat-amenable GLA variants. Pts who received migalastat for ≥2 years in Spain or Portugal were included in this analysis. Data were collected retrospectively and prospectively following enrolment, with ‘baseline’ defined as migalastat start date. All available clinical data since migalastat start are included in the analysis, with overall patient demographics and characteristics described at enrolment. Results Overall, 35 pts (74.3% male) were included in this analysis. At enrolment, median age was 58.0 years, median age at symptom onset was 54.0 years and median time from migalastat start to enrolment was 281.0 days (range 1–733; n=31). The three most common GLA variants were p.F113L (n=21; 60.0%), p.S238N (n=6; 17.1%) and p.R301Q (n=3; 8.6%). As of data cut-off (Nov 2024), 35 pts had median migalastat exposure of 4.8 years (range 2.4–5.9). At first measurement after migalastat start (median 236.0 days N=35; range 6–1,258 for left ventricular mass index LVMi and 169.0 days N=35; range 1–1,044 for eGFR Chronic Kidney Disease Epidemiology Collaboration equation eGFRCKD-EPI), median LVMi was 125.2 g/m² (N=35; range 66–366) and median eGFRCKD-EPI was 92.4 mL/min/1.73 m² (N=35; range 33–113). Using all available retrospective and prospective data, the overall median annualised rate of change in LVMi was 0.16 g/m² (n=33; range –49.3 to 20.9; mean standard deviation (SD) −4.00 15.8). Median annualised rate of change in eGFRCKD-EPI was −1.33 mL/min/1.73 m² (N=35; range −12.8 to 6.6; mean SD −1.54 3.2). Overall, there were no treatment-related treatment-emergent serious adverse events and no discontinuations. Conclusion These data demonstrate that, during a median of 4.8 years of treatment with migalastat, cardiac and renal measures were stable, and migalastat was well tolerated in a population with a majority of late-onset variants and cardiac involvement at baseline.
Azevedo et al. (2025) studied this question.