Open Label Extension Study of Migalastat in Fabry Patients Presented at ASHG

James Radke

At the American Society of Human Genetics (ASHG) annual meeting, 32-months worth of data testing the efficacy of migalastat HCl in Fabry disease patients with amenable mutations was presented.

Daniel G. Bichet, M.D., M.Sc., Professor, Department of Physiology, University of Montreal, presented results from a Phase 3 study (Study 011) including patients who continued on migalastat in an open-label extension (Study 041).

Fabry disease is an X-linked lysosomal storage disorder that leads to excessive deposition of globotriaosylceramide ( GL-3) throughout the body. Skin, eye, kidney, heart, brain, and peripheral nervous system are highly vulnerable. Fabry disease is often difficult to diagnose since signs and symptoms are often nonspecific. Decline in kidney function is a key cause of morbidity and mortality in patients with Fabry disease and glomerular filtration rate (GFR) was the outcome measure studied.

As previously reported for the phase 3 FACETS study, GFR in subjects with amenable GLA mutations remained stable over 18-24 months of treatment, with mean annualized eGFR changes of -0.30 ± 0.66 (CKD-EP  eGFR) and +0.79 ± 1.03 (MDRD eGFR)  L/min/1.73m2/yr. In the poster presented at ASHG, the open label extension of that study, estimated GFR (eGFR) were in 41 patients were: Stratifying patients for gender and baseline proteinuria demonstrated that patients treated with migalastat experienced less decline in kidney function than untreated patients from a previously published natural history study.

Lead author Dr. Daniel Bichet, Full Professor and Section Head, Renal Function & Transport Physiology, University of Montreal, said:

 "Baseline proteinuria levels are among the most predictive indicators of disease prognosis and kidney function decline in Fabry patients. The data presented today show that when comparing patients with similar levels of proteinuria, patients treated with migalastat are more stable in their kidney function versus untreated patients. These results are very encouraging for migalastat as a treatment for Fabry patients with amenable mutations." 

Dr. Jay A. Barth, Chief Medical Officer of Amicus added:

"The additional data on substrate reduction show that we can accurately identify patients who may benefit from migalastat. We look forward to meeting with regulatory agencies starting this quarter as we work to make migalastat available for all amenable Fabry patients as quickly as possible."

Amenable mutations are defined as having an absolute increase of 3% of wild type alpha-Gal A enzyme activity and a relative increase of 20% when exposed to migalastat in a cell-based in vitro assay. As reported earlier, migalastat in all patients with Fabry disease (amenable and non amenable) was not found to be significantly change kidney function measures but subsequent post hoc analysis showed patients enrolled in that study who had amenable mutations in the clinical trial HEK assay did respond well to the drug. It is estimated that approximately 30% to 50% of the Fabry population has mutations that are amenable to migalastat.


Subjects treated with migalastat continue to demonstrate stable renal function in a phase 3 extension study of Fabry disease. Poster presented at American Society Human Genetics Annual Meeting, San Diego CA, Oct 18-22, 2014. Abstract 217S.

Image of fabry eye courtesy wikimedia commons
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