Fabry - AT1001

Fabry disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called α-galactosidase A (α-GAL).  The role of α-GAL within the body is to break down a complex lipid called globotriaosylceramide (GL-3).  Reduced or absent levels of α-GAL activity leads to the accumulation of GL-3 in the affected tissues, including the central nervous system, heart, kidneys, and skin. This accumulation of GL-3 is believed to cause the various symptoms of Fabry disease, including pain, kidney failure, and increased risk of heart attack and stroke.

For more information on Fabry disease, click here.

Amicus is utilizing a new technology in the development of treatments for genetic diseases.  Pharmacological chaperone technology involves the use of small molecules that selectively bind to and stabilize proteins in cells, leading to improved protein folding and trafficking, and increased activity. In our Fabry program, we are investigating the use of AT1001 to bind to destabilized α-galactosidase A enzyme (α-GAL) and thereby restore its intended biological function of degrading globotriaosylceramide (GL-3) substrate in lysosomes.  The chemical name for AT1001 is migalastat hydrochloride and the anticipated trade name for AT1001 is Amigal™.

Phase 1 clinical studies
In 2004, Amicus began human testing of AT1001. Initial Phase 1 studies were conducted in healthy human volunteers to test the safety and tolerability of AT1001.

Single dose and multiple dose studies of AT1001 have been completed in healthy adult volunteers. These studies were randomized, double-blind and placebo controlled studies that were designed to evaluate the safety, tolerability and pharmocokinetics of AT1001. AT1001 demonstrated good oral bioavailability and was generally well-tolerated at all doses with no serious adverse events. Oral administration of AT1001 resulted in a dose-dependent increase in α-GAL levels in WBCs that persisted for 7 days after drug withdrawal. No increase in α-GAL levels was seen in the placebo group.

Phase 2 clinical studies
The primary treatment periods of Phase 2 studies of AT1001 were completed in September 2007. These studies began enrolling subjects in 2005 in medical centers located in the United States, Europe, Australia, and Brazil. These Phase 2 human studies of AT1001 were designed to test the safety and tolerability of several different dose levels of AT1001 that are taken in varying time intervals and to provide preliminary data on effectiveness. For the press release on these trials, click here.