SP002CLINICAL OUTCOMES WITH MIGALASTAT IN PATIENTS WITH FABRY DISEASE BASED ON DEGREE OF RENAL IMPAIRMENT: RESULTS FROM PHASE 3 TRIALS

INTRODUCTION AND AIMS: Fabry disease is a progressive X-linked disorder caused by functional deficiency of α-galactosidase A (α-Gal A) that can lead to multiorgan disorders and early death. Migalastat, an oral pharmacological chaperone, restores lysosomal α-Gal A trafficking and enzyme activity by binding, inducing proper folding, and stabilizing amenable mutant forms of the enzyme. In the Phase 3 FACETS (NCT00925301) and ATTRACT (NCT01218659) trials, migalastat reduced disease substrate, stabilized renal function, and decreased cardiac mass in enzyme replacement therapy (ERT)-naive and ERT-experienced patients, respectively. Here, we assessed outcomes in these patients based on the degree of renal impairment at baseline. METHODS: In FACETS, ERT-naïve patients were randomized to receive 6 months of double-blind treatment with migalastat 150 mg every other day (QOD) or placebo, followed by an additional 18 months of migalastat. In ATTRACT, patients on ERT were randomized to receive 18 months of migalastat 150 mg QOD or continued on ERT, followed by an additional 12 months of migalastat. Clinical endpoints were evaluated for patients with amenable mutations based on baseline renal function (≥30 to <60 mL/min/1.73 m2 and ≥60 mL/min/1.73 m2; eGFRMDRD used for FACETS and mGFRiohexol used for ATTRACT); patients with baseline GFR <30 mL/min/1.73 m2 were excluded from the trials. RESULTS: Regardless of renal function, in FACETS, there was a reduction in kidney interstitial capillary GL-3 inclusions from baseline to month 6 with migalastat (eGFR <60 mL/min/1.73 m2, -0.39, n=3; eGFR ≥60 mL/min/1.73 m2, -0.30, n=22) but not placebo (<60, 0.04, n=2; ≥60, 0.07, n=18). At month 24, lyso-Gb3 and left ventricular mass index (LVMi) decreased and white blood cell (WBC) α-Gal A activity increased with migalastat in both renal subgroups (Table). In ATTRACT, eGFRCKD-EPI remained stable, LVMi decreased, and WBC α-Gal A activity increased, and lyso-Gb3 remained low and stable during 18 months of treatment with migalastat in both renal subgroups (Table). CONCLUSIONS: In both Phase 3 studies, clinical outcomes in patients with Fabry disease and amenable mutations treated with migalastat were similar regardless of renal function.

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