Long-term follow-up of renal function in patients treated with migalastat for Fabry disease

Daniel G Bichet; Roser Torra; Eric Wallace; Derralynn Hughes; Roberto Giugliani; Nina Skuban; Eva Krusinska; Ulla Feldt-Rasmussen; Raphael Schiffmann; Kathy Nicholls

doi:10.1016/j.ymgmr.2021.100786

Long-term follow-up of renal function in patients treated with migalastat for Fabry disease

Mol Genet Metab Rep. 2021 Aug 4:28:100786. doi: 10.1016/j.ymgmr.2021.100786. eCollection 2021 Sep.

Authors

Affiliations

¹ Department of Medicine, Hôpital du Sacré-Coeur, University of Montréal, Montreal, Quebec, Canada.
² Inherited Renal Disorders, Nephrology Department, Fundació Puigvert, REDINREN, IIB Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
³ Department of Medicine, University of Alabama, Birmingham, AL, USA.
⁴ Lysosomal Storage Disorders Unit, Royal Free London NHS Foundation Trust and University College London, London, UK.
⁵ Medical Genetics Service, Department of Genetics, Institute of Biosciences, Institute of Basic Health Sciences, Faculty of Medicine, Faculty of Pharmacy (UFRGS) and, National Institute of Population Medical Genetics (INAGEMP), Porto Alegre, Brazil.
⁶ Amicus Therapeutics, Inc., Cranbury, NJ, USA.
⁷ Department of Medical Endocrinology and Metabolism, Rigshospitalet, National University Hospital, Copenhagen University, Copenhagen, Denmark.
⁸ Institute of Metabolic Disease, Baylor Scott & White Research Institute, Dallas, TX, USA.
⁹ Department of Nephrology, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.

Abstract

The effect of migalastat on long-term renal outcomes in enzyme replacement therapy (ERT)-naive and ERT-experienced patients with Fabry disease is not well defined. An integrated posthoc analysis of the phase 3 clinical trials and open-label extension studies was conducted to evaluate long-term changes in renal function in patients with Fabry disease and amenable GLA variants who were treated with migalastat for ≥2 years during these studies. The analysis included ERT-naive (n = 36 [23 females]; mean age 45 years; mean baseline estimated glomerular filtration rate (eGFR), 91.4 mL/min/mL/1.73 m²) and ERT-experienced (n = 42 [24 females]; mean age, 50 years; mean baseline eGFR, 89.2 mL/min/1.73m²) patients with amenable variants who received migalastat 123 mg every other day for ≥2 years. The annualized rate of change from baseline to last observation in estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration equation (eGFR_CKD-EPI) was calculated by both simple linear regression and a random coefficient model. In ERT-naive patients, mean annualized rates of change from baseline in eGFR_CKD-EPI were - 1.6 mL/min/1.73 m² overall and - 1.8 mL/min/1.73 m² and - 1.4 mL/min/1.73 m² in male and female patients, respectively, as estimated by simple linear regression. In ERT-experienced patients, mean annualized rates of change from baseline in eGFR_CKD-EPI were - 1.6 mL/min/1.73 m² overall and - 2.6 mL/min/1.73 m² and - 0.8 mL/min/1.73 m² in male and female patients, respectively. Mean annualized rate of change in eGFR_CKD-EPI in ERT-naive patients with the classic phenotype (defined by white blood cell alpha galactosidase A [α-Gal A] activity of <3% of normal and multiorgan system involvement) was -1.7 mL/min/1.73 m². When calculated using the random coefficient model, which adjusted for sex, age, and baseline renal function, the annualized eGFR_CKD-EPI change was minimal (mean: -0.1 and 0.1 mL/min/1.73 m² in ERT-naive and ERT-experienced patients, respectively). In conclusion, patients with Fabry disease and amenable GLA variants receiving long-term migalastat treatment (≤8.6 years) maintained renal function irrespective of treatment status, sex, or phenotype.

Keywords: Chaperone; Classic phenotype; Efficacy; Fabry disease; GLP-HEK, Good Laboratory Practice-validated human embryonic kidney; Gb3, globotriaosylceramide; LVMi, left ventricular mass index; Migalastat; Q1, quartile 1; Q3, quartile 3; RI, renin inhibitor; Renal function; eGFRCKD-EPI, estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration equation; α-Gal A, α-galactosidase A.