Oral Chaperone Therapy Migalastat for Treating Fabry Disease: Enzymatic Response and Serum Biomarker Changes After 1 Year.

Long-term effects of migalastat therapy in clinical practice are currently unknown. We evaluated migalastat efficacy and biomarker changes in a prospective, single-center study on 14 patients with Fabry disease (55 ± 14 years; 11 men). After 1 year of open-label migalastat therapy, patients showed significant changes in alpha-galactosidase-A activity (0.06-0.2 nmol/minute/mg protein; P = 0.001), left ventricular myocardial mass index (137-130 g/m2 ; P = 0.037), and serum creatinine (0.94-1.0 mg/dL; P = 0.021), accounting for deterioration in estimated glomerular filtration rate (87-78 mL/minute/1.73 m2 ; P = 0.012). The enzymatic increase correlated with myocardial mass reduction (r = -0.546; P = 0.044) but not with renal function (r = -0.086; P = 0.770). Plasma globotriaosylsphingosine was reduced in therapy-naive patients (10.9-6.0 ng/mL; P = 0.021) and stable (9.6-12.1 ng/mL; P = 0.607) in patients switched from prior enzyme-replacement therapy. These first real-world data show that migalastat substantially increases alpha-galactosidase-A activity, stabilizes related serum biomarkers, and improves cardiac integrity in male and female patients with amenable Fabry disease mutations.