Migalastat for the treatment of Fabry disease

Abstract

ABSTRACTIntroduction: Fabry disease, a rare X-linked disorder of α-galactosidase A deficiency, leads to progressive multiorgan damage.Areas covered: Enzyme replacement therapy (ERT) is the current standard of care for Fabry disease; however, many patients progress despite treatment and the intravenous infusions present several challenges. Migalastat, an orally administered, small molecule pharmacological chaperone, binds to and stabilizes specific mutant forms of α-galactosidase A. Migalastat is approved in several countries for Fabry disease in patients with amenable GLA mutations; amenable mutations are identified using a good laboratory practice-validated assay. Data from clinical trials demonstrated that migalastat effectively reduces disease substrate, stabilizes renal function, decreases cardiac mass and improves gastrointestinal signs and symptoms in patients with Fabry disease and amenable mutations. Across trials, migalastat was generally well tolerated; headache was the most frequently reported treatment-emergent adverse event. Long-term treatment with migalastat was associated with sustained reduction in left ventricular mass index and evidence of left ventricular hypertrophy regression; migalastat was generally well tolerated over 48 months of treatment. An ongoing Phase III extension study will provide further evidence of the long-term safety and efficacy of migalastat.Expert opinion: Given the convenience of the orally administered small molecule and the efficacy and safety demonstrated in pivotal Phase III trials, migalastat offers a viable alternative to ERT for patients with Fabry disease and migalastat-amenable mutations.