Amigal™ for Fabry Disease

Amigal (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.

How Amigal Works

Amigal 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 II studies of its lead product, Amigal, for Fabry disease. If you are interested in participating in a clinical trial, please click here.

Initial data from the first four Fabry disease patients enrolled in one of the Phase II studies showed that the level of activity of the enzyme known to be deficient in Fabry disease after six weeks of treatment was, on average, more than five-fold higher than before treatment.

Phase I studies in healthy volunteers demonstrated that Amigal was well tolerated, even at the highest doses, without any drug-related adverse events.  In addition, Amigal 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 Amigal for the treatment of Fabry disease. In May 2006, the European Commission granted orphan medicinal product designation for Amigal. Orphan designation is granted by many regulatory agencies in order to promote the development of therapies for rare diseases.