Pompe – AT2220

Pompe disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called acid α-glucosidase (Gaa). The role of Gaa within the body is to break down glycogen, the form of sugar stored in living cells for use as energy.  Reduced or absent levels of Gaa activity leads to the accumulation of glycogen in the affected tissues, including the heart, skeletal muscles (including those involved with breathing), liver, and nervous system. This accumulation of Gaa is believed to cause progressive muscle weakness and respiratory insufficiency in individuals with Pompe disease. Pompe disease can occur in infants, toddlers, or adults, and the prognosis varies according to the time of onset and severity of symptoms.

For more information on Pompe 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 Pompe program, we are investigating the use of AT2220 to bind to destabilized GAA enzyme (acid alpha glucosidase or acid α-glucosidase) and thereby restore its intended biological function of degrading glycogen substrate in lysosomes. The chemical name for AT2220 is 1-deoxynojirimycin hydrochloride.

Following successful completion of multiple Phase 1 studies of AT2220 in healthy volunteers, Amicus initiated a Phase 2 clinical trial of AT2220 in adults with Pompe disease in June, 2008. Based on safety data from both preclinical and Phase 1 studies, the approved Phase 2 trial protocol involved initial treatment with a high dose of AT2220. Two patients enrolled in the trial experienced self-reported muscle weakness and subsequently withdrew from the trial. The events were categorized by the site investigator as serious and probably related to treatment with AT2220.

In Feburary 2009, Amicus announced the Company has suspended enrollment for the Phase 2 clinical trial of its investigational drug AT2220 for the treatment of Pompe Disease and that it has received a clinical trial hold from the FDA (Food and Drug Administration).

In September 2009, the FDA agreed to Amicus' proposal for a Phase 1 study and subsequently converted the clinical hold of AT2220 to a partial hold to allow the conduct of this study.   In October 2009 the Company initiated a Phase 1 study of AT2220.  The primary objective of this study is to evaluate the pharmacokinetics of AT2220 in muscle tissue in healthy adult subjects.  Results from this study are expected in the first half of 2010.
For the press release on these clinical trials, click here

Additional information regarding Pompe clinical trial(s) sponsored by Amicus can be found by visiting www. clinicaltrials.gov and searching the keyword “Amicus".