Approved treatments for Fabry disease

Last updated May 30, 2024, by Lindsey Shapiro, PhD
Fact-checked by Ana de Barros, PhD

A number of medications are approved to treat Fabry disease, and all aim to prevent organ damage and ease disease symptoms caused by the accumulation of certain fatty molecules inside cells.

Fabry disease is a rare genetic condition caused by mutations in the GLA gene, which provides the instructions to make an enzyme called alpha-galactosidase A (alpha-Gal A).

This enzyme is required for breaking down fatty molecules such as globotriaosylceramide (Gb3) inside cells. But it’s either missing or malfunctioning in Fabry patients, which causes Gb3 to accumulate to toxic levels, leading to organ damage mainly in the heart, kidneys, and nervous system.

Two main classes of therapies are currently available for Fabry patients: enzyme replacement therapy and chaperone therapy. While these work via different mechanisms, both are designed to restore alpha-Gal A activity to reduce the toxic buildup of Gb3.

Enzyme replacement therapy

Enzyme replacement therapy, or ERT, has been available since 2001 as the main treatment approach for people with Fabry, playing a vital role in disease management.

It involves regular administrations of a lab-made version of the alpha-Gal A enzyme, usually via an into-the-vein infusion. This temporarily provides patients with a functioning enzyme to replace the one that’s missing or defective.

ERT is expected to reduce the toxic accumulation of Gb3 and other fatty molecules, thereby slowing or preventing the progression of organ damage that characterizes the disease.

Still, because the infused enzyme normally lasts only a few hours in circulation, and the body remains unable to produce a functional alpha-Gal A on its own, patients will require lifelong ERT infusions to maintain appropriate levels of the working enzyme.

Currently, two ERTs — Fabrazyme (agalsidase beta) and Elfabrio (pegunigalsidase alfa-iwxj) — are approved in the U.S. for Fabry disease. Both are administered as an intravenous infusion every other week.

Fabrazyme

Fabrazyme, sold by Sanofi, was approved by the U.S. Food and Drug Administration (FDA) in 2003, becoming the first therapy specifically approved for Fabry disease in the U.S. It is now available to adults and children, 2 and older, regardless of genetic variant, gender, or disease severity.

The medication contains agalsidase beta, a functional version of the alpha-Gal A enzyme that’s produced in hamster ovary cells. This enzyme is virtually identical to the enzyme that’s naturally produced in the body.

Elfabrio

Elfabrio, marketed by Chiesi Global Rare Diseases, is a newer ERT that gained U.S. approval in 2023 for adults with confirmed Fabry disease.

It contains pegunigalsidase alfa, a version of alpha-Gal A produced in plant cells that’s engineered to have a chemical modification called PEGylation. This modification helps to make the enzyme more stable, thereby prolonging its presence in the bloodstream.

Chaperone therapy

Chaperone therapy is a more recent Fabry disease treatment strategy that uses small molecules to correct the folding and stabilize the existing alpha-Gal A to help it perform its function.

These small molecules mimic the function of naturally occurring proteins called chaperones, which participate in a number of cellular processes, including ensuring that other proteins acquire the proper structure and are transported to their correct location inside cells.

In Fabry disease, the abnormal alpha-Gal A enzyme is degraded prematurely by the cell’s quality control mechanisms. This prevents it from reaching lysosomes, cellular organelles that serve as recycling centers for faulty or unneeded components and where the enzyme exerts its functions.

By stabilizing the mutated alpha-Gal A and correcting its folding, chaperone therapy can allow more enzymes to reach the lysosomes to carry out their function.

Notably, however, chaperone therapy is only suitable for patients whose mutations result in the production of a misfolded and nonfunctional alpha-Gal A. The approach will not work if patients produce no enzyme at all.

Currently, Galafold (migalastat) is the only chaperone therapy approved for Fabry disease.

Galafold

Galafold was approved in the U.S. in 2018 for adults with a confirmed diagnosis of Fabry disease and certain GLA mutations. A search engine is available to determine if a person’s mutations are amenable to Galafold treatment.

Developed by Amicus Therapeutics, it is administered as an oral capsule every other day.

The medication works by binding to patients’ faulty alpha-Gal A enzyme and helping it to acquire a more normal shape, which facilitates its proper trafficking to lysosomes.

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