Amicus Fabry Drug Shows Good Cardiac Outcomes

James Radke

Amicus Therapeutics announced additional positive data on important secondary cardiac endpoints from its second Phase 3 looking at the safety and efficacy of migalastat in patients with Fabry disease. While Fabry disease is a lysosomal disease in which a key problem is a decline in kidney function, a leading cause of death in Fabry patients is from cardiac complications.

Nicholls et al presented their poster at the American Society of Nephrology (ASN) Kidney Week 2014. In the study,  patient swho switched from enzyme replacement therapy (Fabrazyme un U.S. and Replagal in Europe) to migalastat showed a statistically significant decrease from baseline to month 18 in left ventricular mass index (LVMi). LVMi is a measure of cardiac hypertrophy.

Professor Ales Linhart, MD, PhD, a leading expert in the cardiac manifestations of Fabry disease from Charles University of Prague said:

"Cardiac disease represents a major cause of morbidity and mortality in Fabry patients that is not adequately addressed with currently available treatment."

"The data showing further regression of left ventricular mass in patients switched from ERT to migalastat in this study are very promising since in other cardiac conditions a reduction of cardiac mass typically translates to significant improvements in long term outcomes."

As reported earlier, migalastat was comparable to enzyme replacement therapy in primary outcome measures (renal function) in this phase 3, open-label study in which patients with Fabry disease and amenable mutations who had been on enzyme replacement therapy for at least a year were randomized to receive oral migalastat (n=36), or continue their enzyme replacement therapy (n=24).

Dr. Kathy Nicholls, nephrologist from Royal Melbourne Hospital and University of Melbourne, and investigator with 7 years experience in treating Fabry patients in clinical studies of migalastat, said:

 "Fabry patients randomized to switch from ERT to Migalastat showed stability in renal function at least comparable to those who continued on ERT. The new data on cardiac mass and clinical events are encouraging. An oral therapy for Fabry disease is very attractive to patients."

Amicus expects to submit a marketing application for migalastat monotherapy in Europe, and is scheduled to meet with the European Medicines Agency in the fourth quarter of this year. Amicus a so plans to meet with the  U.S. Food and Drug Administration (FDA) in the first quarter of 2015 to discuss the data and determine the fastest U.S. registration pathway for migalastat. Currently, the only approved medication in the United States for patients with Fabry disease is the enzyme replacement therapy, Fabrazyme. Shire's Replagal is available in other countries (as is Fabrazyme).


Nicholls K, Bichet DG, Giugliani R, et al.. Migalastat and Enzyme Replacement Therapy Have Comparable Effects on Renal Function in Fabry Disease: Phase 3 Study Results.  Presented at American Society of Nephrology Kidney Week 2014; Philadelphia PA; November 11-16, 2014.
Figure of cardiac MRI from Germain’s review article on Fabry disease published in the open source journal, Orphanet Journal of rare Diseases. Figure of left ventricular mass index from Amicus’ presentation posted November 15, 2015
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