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 2 and Phase 2 Extension Clinical Studies
Amicus completed multiple Phase 2 studies of AT1001 for the treatment of Fabry disease.  In total, twenty-six male and female subjects were treated for either 12 or 24 weeks.  Twenty-three of the 26 subjects continued to receive treatment in an ongoing Phase 2 Extension Study designed to evaluate the long-term safety and efficacy of AT1001.

Results from the Phase 2 studies indicated that treatment with Amigal was generally well-tolerated, with no drug-related serious adverse events.  The most common adverse events were headache, arthralgia and diarrhea.  In subjects identified as responders to AT1001, treatment resulted in increased levels of the target enzyme (α-Gal A), as measured in white blood cells and in the kidney, and reduced levels of the target substrate (GL-3), as measured in renal interstitial capillary cells from kidney biopsies and in urine.

In February 2010, the Company announced additional preliminary results from its ongoing Phase 2 extension study.  Treatment with AT1001 continues to be generally well-tolerated, with no drug-related serious adverse events. Renal function is being evaluated by two measures in the extension study, estimated glomerular filtration rate (eGFR) and proteinuria.  Preliminary data indicate that eGFR has remained stable out to 2-3 years for all subjects continuing in the extension study and the average annual rate of change in eGFR in subjects identified as responders to migalastat HCl, excluding hyperfiltrators, was +2.0 mL/min/1.73m2.  Additionally, trends of reduced proteinuria continued to be observed in subjects identified as responders to AT1001.

Twenty-one of the 26 subjects continue to receive treatment in an ongoing extension study.
For the press release on these clinical trials, click here.