Amigal™ ( AT1001) for Fabry Disease

AT1001 (migalastat hydrochloride) is an experimental, oral therapy for the treatment of Fabry disease and belongs to a class of molecules known as pharmacological chaperones.

Fabry Disease

Fabry disease is a lysosomal storage disorder resulting from a deficiency in the key metabolic enzyme α-galactosidase A (α-GAL). This enzyme is responsible for breaking down a specialized type of fat molecule known as globotriaosylceramide (GL-3) in the lysosome. The enzyme deficiency is caused by inherited genetic mutations, which result in the production of misfolded α-GAL protein. The absent or defective enzyme activity leads to the build-up of GL-3 in certain cells. Over time, this can cause damage to specific areas within the body, including the kidneys, heart, nervous system, and skin. For more information on Fabry disease, please click here.

AT1001 for Fabry Disease

AT1001 acts by selectively binding to the misfolded enzyme responsible for Fabry disease, α-GAL. This may increase the enzyme’s stability and promote the proper folding, processing, and trafficking of the enzyme from the endoplasmic reticulum to its final destination, the lysosome, the area of the cell where the enzyme does its work. Once it reaches the lysosome, the pharmacological chaperone is displaced and the enzyme can perform its normal biological function, which is the breakdown of its natural substrate, GL-3.

Clinical Progress

Amicus is currently conducting Phase 2 studies of its lead product, AT1001, for Fabry disease. If you are interested in participating in a clinical trial, please click here.

In Phase 1 studies in healthy volunteers, AT1001 was well tolerated.  In addition, AT1001 was shown to have high oral bioavailability and good pharmacokinetics. Finally, studies showed a statistically significant and dose-related increase in the level of activity of the target enzyme in healthy volunteers.

In February 2004, the FDA granted Amicus orphan designation for AT1001 for the treatment of Fabry disease. In May 2006, the European Commission granted orphan medicinal product designation for AT1001. Orphan designation is granted by many regulatory agencies in order to promote the development of therapies for rare diseases.