The European Commission has granted approval for the oral small molecule pharmacological chaperone Galafold ( Migalastat ) as a first line therapy for long-term treatment of adults and adolescents aged 16 years and older with a confirmed diagnosis of Fabry disease ( alpha-galactosidase A deficiency ) and who have an amenable mutation.

The EC approval was based on clinical data from two phase 3 pivotal studies in both treatment naïve ( Study 011, or FACETS ) and enzyme replacement therapy ( ERT ) switch patients ( Study 012, or ATTRACT ), as well as ongoing long-term extension studies.

Galafold is a first-in-class chaperone therapy approved in the EU as a monotherapy for Fabry disease in patients with amenable mutations. Galafold works by stabilizing the body’s own dysfunctional enzyme, so it can clear the accumulation of disease substrate in patients who have amenable mutations.
A proprietary in vitro assay ( Galafold Amenability Assay ) was used to classify more than 800 known GLA mutations as amenable or not-amenable to treatment with Galafold.
The current label includes all 269 GLA mutations that have been identified and determined to be amenable based on the Galafold Amenability Assay, which represent between 35% and 50% of the currently diagnosed Fabry population.

Galafold is not intended for concomitant use with enzyme replacement therapy.

Galafold is not recommended for use in patients with Fabry disease who have severe renal impairment ( less than 30 mL/min/1.73 m2 ).

The safety and efficacy of Galafold in children 0–15 years of age have not yet been established.

No dosage adjustments are required in patients with hepatic impairment or in the elderly population.

There is very limited experience with the use of this medicine in pregnant women. While taking Galafold, patients should use effective birth control should be used. It is not known whether Galafold is excreted in human milk.

Fabry disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called alpha-galactosidase A ( alpha-Gal A ), which are the result of mutations in the GLA gene.
The primary biological function of alpha-Gal A is to degrade specific lipids in lysosomes, including globotriaosylceramide ( GL-3 ).
Reduced or absent levels of alpha-Gal A activity lead to the accumulation of GL-3 in the affected tissues, including the central nervous system, heart, kidneys, and skin.
Progressive accumulation of GL-3 is believed to lead to the morbidity and mortality of Fabry disease, including pain, kidney failure, heart disease, and stroke.
The symptoms can be severe, differ from patient to patient, and begin at an early age.
All Fabry disease is progressive and leads to organ damage regardless of the time of symptom onset. ( Xagena )

Source: Amicus Therapeutics, 2016

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