EC Approves First Oral, Precision Medicine for Rare Disease, Fabry


European Commission (EC) fully approved the first oral treatment as well as the first precision medicine, Galafold™ (migalastat) of US based Amicus Therapeutics for the treatment of a rare, genetic disorder, Fabry disease.

amicus_therapeutics official logo

Galafold™ will be given as a first line therapy to the Fabry disease patients or who have an amenable mutation for long-term treatment. Amicus began the supply in the German market on May 30, 2016 and is preparing for the markets of major European countries.

Fabry disease occurs due to the deficiency of an enzyme, alpha-galactosidase A (alpha Gal A) due to the mutation in GLA gene. It is a lysosomal storage disease inherited in a X- linked manner. Alpha-Gal A degrades specific lysosomal lipids including GL-3 (globotriaosylceramide).

lysosomal storage disease

Figure 1. Lysosomes and other organelles (Photo credit: Fabry disease, Genetics Home Response, NIH U.S. National Library of Medicine)

In the absence of alpha-Gal A, GL-3 gets accumulated in the affected tissues including heart, kidney, central nervous system, skin. Progressive accumulation of GL-3 for years leads to the morbidity or mortality of the patient due to stroke, kidney failure, heart disease etc.

sign and symptoms of fabry disease

Figure 2. Sign and symptoms of Fabry disease (Photo credit: adapted from Eur Heart J. 2013 Mar;34(11):802-8. doi: 10.1093/eurheartj/ehs166)

Galafold™ is a first-in-class chaperone therapy for Fabry disease. It serves as a monotherapy in patients with amenable mutations. Its active agent, migalastat is a pharmacological chaperone which is engineered to selectively and reversibly bind to specific mutant forms of alpha-Gal A present in patients with GLA mutation. Galafold™ stabilizes the body’s own faulty enzyme, so it can dislodge the accumulation of disease substrate in the patients with the amenable mutation. Its broad label encompasses 269 Fabry causing mutation which includes almost 35% to 50% of all patients with Fabry disease. Galafold™ is for the patients of 16 years age or above.

Galafold fabry disease

Figure 3. Molecular mechanism of Galafold™ (Photo credit: Amicus Therapeutics)

The EC approval was based on the results of two Phase III study in both ERT switch patients and treatment-naive patients as well as on-going long-term extension studies. Galafold™ can stabilize the renal function for up to 18 months in ERT switch patients and for 30 months in treatment naive patients followed by improvement in cardiac function.

Currently, the Enzyme Replacement Therapy (ERT) is available for the treatment of Fabry disease. The recombinant alpha-Gal A, administered intravenously as the ERT are Fabrazyme® (agalsidase β) of Genzyme Corp. and Replagal (agalsidase α) of TKT Corp. They are approved in most European countries and Fabrazyme was approved in the US in 2003.

In ERT, the patients are injected with the biologically functional protein which goes into the lysosomes through specific receptors on the surface of the target cells which in turn reverses the metabolic and pathological abnormalities in the cells.

François Eyskens, MD, PhD, Department of Experimental Medicine and Pediatrics, University of Antwerp, Antwerpen, stated, “During my 20 years in treating Fabry disease, I am convinced that it is underdiagnosed and that significant unmet need remains among these patients. Galafold is an innovative oral precision medicine with a unique mechanism of action that has demonstrated compelling results in naïve and treatment-experienced Fabry patients who have amenable mutations. I am looking forward to offering a differentiated treatment option for the many Fabry patients who have an amenable mutation”.

The EC approval has wide opened the door of this new treatment option for Fabry disease for the global market. Amicus anticipates a meeting with US FDA in mid 2016 to chalk out a pathway for the US entry of Galafold™.

Here is a nice video explaining the Pharmacological chaperone and lysosomal storage disease (Source:

Featured image credit: The neo-gothic facade of Florence Cathedral in Opera di Santa Maria del Fiore. Florence Italy © Alvaro German Vilela (Stock Photo ID: 50437022)

One comment

  1. Thanks for sharing such important knowledge. as a medical science student this is really helpful for me.


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