Amicus Getting Ready to Submit NDA for Migalastat to Treat Fabry

James Radke

Amicus Therapeutics announced the U.S. Food and Drug Administration (FDA) has given the company the go-ahead to submit a new drug application (NDA) for their drug migalastat for the treatment of Fabry disease.
The announcement comes after several meetings between Amicus and the FDA, and both parties have agreed that sufficient data is now available for the latter to make an informed decision on the safety and efficacy of the drug. The company plans to submit the NDA in the 4th quarter of 2017.
Fabry disease is an X-linked lysosomal storage disorder due to a deficiency of alpha-galactosidase A (alpha-Gal A) which degrades specific lipids in lysosomes, including globotriaosylceramide (GL-3). The net result is excessive deposition of glycosphingolipids throughout the body that can impact multiple organs, including skin, eyes, kidneys, heart, brain, and the peripheral nervous system are highly vulnerable.

Currently, Genzyme’s Fabrazyme is the only approved treatment for Fabry disease in the United States, however, in Europe, Amicus’ migalastat (Galafold), and Shire’s Replagal, are approved, too.
Migalastat, a chaperone therapy, works by stabilizing alpha-Gal A so it can clear the accumulation of disease substrate in patients who have amenable mutations, and getting the drug to the FDA for review has been a challenge for Amicus.
In 2012, data from Amicus’ clinical trial testing the efficacy of migalastat in Fabry patients did not meets its primary endpoint and few were optimistic that the drug would ever be approved. Further analysis, however, indicated that patients with ‘amenable mutations’ – 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 – were more responsive to migalastat.
It is estimated that approximately 30% to 50% of the Fabry population has mutations that are amenable to migalastat.
In 2015, Amicus announced another setback when they stated the FDA wanted the company to conduct an additional study assessing the effects of migalastat on gastrointestinal symptoms. The FDA has since reversed that decision and is no longer asking the company to conduct another trial.
“We are moving ahead expeditiously with our NDA submission and accelerating the U.S. pathway for migalastat. Today is a seminal moment in the development of migalastat and a testament to the dedication and perseverance of the patients, physicians and employees who have worked so hard on the development of this precision medicine,” said John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics.

Jack Johnson, Founder and Executive Director of the Fabry Support & Information Group (FSIG) added, "With significant unmet needs and a lack of treatment choices for people living with Fabry disease in the U.S., we may be one step closer to a new oral therapy. Amicus has been a true partner for the Fabry community for more than a decade, and I look forward to potentially having a new oral precision medicine available to patients with amenable mutations in the U.S."
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