Rare Disease Report

Amicus to Submit NDA for Migalastat to Treat Fabry Disease the End of 2015

SEPTEMBER 15, 2015
James Radke, PhD
Amicus Therapeutics announced it is on track to submit a New Drug Application (NDA) to the FDA in the 4th quarter of 2015 for the drug migalastat to treat Fabry disease patients. The company stated a recent Pre-NDA meeting with the FDA clarified that reduction in disease substrate [kidney interstitial capillary globotriaosylceramide (GL-3)] will serve as the primary endpoint to be supported by the totality of data from completed clinical studies.
In addition to the NDA submission, Amicus plans to submit the protocol for a Phase 4 study examining the effects of migalastat on gastrointestinal symptoms in these patients.
In a press release, John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics said, "The guidance provided by FDA during the Pre-NDA meeting further reinforces our confidence in the NDA package and post-marketing confirmatory study we are preparing for submission by the end of this year. In addition, our marketing submission for migalastat in Europe is already being reviewed under Accelerated Assessment and an Opinion is expected by year-end. With defined regulatory pathways for migalastat in both the U.S. and EU, we are rapidly executing our global strategy to bring this novel personalized medicine to as many people living with Fabry disease as quickly as possible."

Migalastat's Regulatory Journey

The path to gain approval of Migalastat has been a rocky one. In 2012, data from Amicus’ clinical trial testing the efficacy of migalastat in Fabry patients did not meets its primary endpoint and many (i.e., investors) were not optimistic. However, further analysis indicated that patients with ‘amenable mutations’ were more responsive to migalastat and since then, the data has been more optimistic. 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. It is estimated that approximately 30% to 50% of the Fabry population has mutations that are amenable to migalastat.

What is Fabry Disease?

Fabry disease is an X-linked lysosomal storage disorder that leads to excessive deposition of glycosphingolipids throughout the body. Skin, eye, kidney, heart, brain, and peripheral nervous system are highly vulnerable. Fabry disease is caused by deficiency of an enzyme called alpha-galactosidase A (alpha-Gal A) which degrades specific lipids in lysosomes, including globotriaosylceramide (GL-3). The accumulation of GL-3 is believed to cause the various symptoms of Fabry disease.
Symptoms do appear in childhood but often go undiagnosed for several years. As the disease progressive, most patients with Fabry disease die in their fourth or fifth decade due to complications arising from renal or cardiovascular problems.

Currently, Genzyme’s Fabrazyme is the only approved treatment for Fabry disease in the United States.  Fabrazyme is also approved in Europe and elsewhere, as is Shire’s Replagal.


Amicus Therapeutics Plans to Submit New Drug Application (NDA) for Migalastat for Fabry Disease Following Positive Pre-NDA Meeting With FDA [news release]. Cranbury, NJ: Amicus Therapeutics; September 15, 2015. https://globenewswire.com/news-release/2015/09/15/768298/10149333/en/Amicus-Therapeutics-Plans-to-Submit-New-Drug-Application-NDA-for-Migalastat-for-Fabry-Disease-Following-Positive-Pre-NDA-Meeting-With-FDA.html

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