Gaucher – AT2101

Gaucher disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called β-glucocerebrosidase (GCase). The role of GCase within the body is to break down a complex fatty substance called glucocerebroside.  Reduced or absent levels of GCase activity leads to the accumulation of glucocerebroside in the affected tissues, including the spleen, liver, lungs, bone marrow, and sometimes in the brain. This accumulation of GCase is believed to cause the various symptoms of Gaucher disease, including an enlarged liver and spleen, skeletal disorders, and, in some instances, lung, kidney, and central nervous system impairment. Individuals with Gaucher disease may also bruise easily and experience pain and fatigue due to anemia and low blood platelets.

For more information on Gaucher 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 Gaucher program, we are investigating the use of AT2101 to bind to destabilized glucocerebrosidase (GCase) enzyme and thereby restore its intended biological function of degrading glucocerebroside (GlcCer) substrate in lysosomes. The chemical name for AT2101 is isofagomine (IFG) tartrate and the anticipated trade name for AT2101 is Plicera™.

Phase 1 clinical studies
In 2006, Amicus began human testing of AT2101. Initial Phase 1 studies were conducted in healthy human volunteers to test the safety and tolerability of AT2101.

Single dose and repeat dose studies of AT2101 have been completed in healthy adult volunteers. AT2101 demonstrated good oral bioavailability and linear pharmacokinetics. In a repeat-dose Phase 1 clinical study, oral administration of AT2101 resulted in a statistically significant, dose-related increase in white blood cell (leukocyte) GCase levels: during the 7-day treatment period, leukocyte GCase levels were increased up to approximately 3.5 fold over baseline levels.  AT2101 demonstrated a half-life of ~14 hours in plasma, while enzyme levels remained elevated for more than a week after removal of the drug. In healthy volunteers, AT2101 was generally safe and well-tolerated at all doses; no serious adverse events were observed during Phase 1 testing.

Phase 2 clinical studies
AT2101 currently is being studied in people who have Gaucher disease. These studies began enrolling subjects in March 2007 and are being conducted in medical centers located throughout the United States and the United Kingdom, Germany, and Israel.

One Phase 2 study was completed in March 2008.  For information about the positive results of this trial, click here.

An additional study is currently being conducted and is enrolling adult subjects who currently are not receiving enzyme replacement therapy or substrate reduction therapy.

Enrollment criteria, site locations, and specifics regarding these Phase 2 Gaucher studies may be found by visiting www.clinicaltrials.gov and searching the keyword “Amicus” or by clicking here.