Migalastat Preserved Renal Function Over Long Term in Patients With Fabry Disease

New data show the therapy led to minimal changes in renal function, even after more than 8 years.

New long-term data show that patients with Fabry disease who are treated with migalastat (Galafold) experienced stable renal function after 2 years or more on the drug.

The report offers some of the first data regarding the long-term data regarding the medication, which was approved by the FDA in 2018. The study was published in the journal Molecular Genetics and Metabolism Reports.

Fabry disease is a rare lysosomal storage disease caused by a mutation of the GLA gene. The mutation leads to buildup of globotriaosylceramide (Gb3) throughout the body, including in the kidneys. Renal manifestations of the disease—as well as likely associated cardiac events—are a significant cause of mortality and morbidity in patients with Fabry, noted corresponding author Daniel G. Bichet, MD of the University of Montreal, and colleagues.

Enzyme replacement therapy (ERT), in combination with the oral chaperone migalastat, has become the standard treatment for people with Fabry disease. The investigators explained that migalastat works by targeting the lysosomal enzyme lysosomal enzyme α-galactosidase A (α-Gal A), which is functionally deficient in patients with Fabry.

“As a small molecule pharmacological chaperone, migalastat binds to and stabilizes amenable mutant forms of α-Gal A in the endoplasmic reticulum, facilitating trafficking of α-Gal A to lysosomes and restoring endogenous enzyme activity,” Bichet and colleagues wrote.

Previous reports, including the phase 3 clinical trials for migalastat, showed that patients on the medication had stable renal function. However, those studies were based on shorter time frames of 24 months or less.

In the new study, the authors conducted a post-hoc analysis to look at the long-term renal-function changes in patients with amenable GLA variants who were given migalastat for 2 or more years as part of the phase 3 trials and/or long-term open-label extension studies.

A total of 78 patients were included in the analysis. Of those, 36 were ERT-naive, and 42 were ERT-experienced. The 2 groups had average ages of 45 years and 50 years, respectively. The ERT-naive group had a mean baseline estimated glomerular filtration rate (eGFR) of 91.4 mL/min/mL/1.73 m2, while the ERT-experienced group had a mean baseline eGFR of 89.2 mL/min/1.73 m2.

All of the patients were prescribed migalastat at a dose of 123 mg every other day. The patients all took the drug for at least 2 years, and up to 8.6 years. Investigators then calculated an annualized rate of change for the patients, using the Chronic Kidney Disease Epidemiology Collaboration equation.

In the ERT-naive cohort, the mean annualized rates of change from baseline were -1.6 mL/min/1.73 m2 overall. Stratified by gender, male patients had a mean annualized change rate of -1.8 mL/min/1.73 m2 and females had a change rate of -1.4 mL/min/1.73 m2.

In the RT-experienced cohort, the overall mean annualized rate of change was -1.6 mL/min/1.73 m2, -2.6 mL/min/1.73 m2for male patients, and -0.8 mL/min/1.73 m2for female patients.

This translated to a minimal annualized change in renal function from baseline.

Bichet and colleagues said the data show migalastat led to preserved renal function across a broad range of patients.

“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,” they wrote.


Bichet DG, Torra R, Wallace E, et al. Long-term follow-up of renal function in patients treated with migalastat for Fabry disease. Mol Genet Metab Rep. Published online August 4, 2021. doi:10.1016/j.ymgmr.2021.100786