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The following information is taken from the Pompe Community Update Newsletter with permission by Amicus:

Summer 2011

Amicus Therapeutics’ Pompe Program is proceeding with a Phase 2 co-administration study of AT2220, the investigational pharmacological chaperone for Pompe disease, and enzyme replacement therapy (ERT). AT2220-010 is a proof-of-concept clinical research study to determine if an oral dose of AT2220 (duvoglustat hydrochloride) before an infusion of Lumizyme or Myozyme can be co-administered safely with the ERT and whether AT2220 can impact the activity and uptake of the ERT in key tissues.

AT2220, like all of Amicus’ pharmacological chaperones, is an orally administered, small molecule drug designed to increase the activity of a specific protein. Pharmacological chaperones selectively bind to and stabilize the target enzyme naturally produced by a person’s cells. This leads to increased enzyme activity and potentially a decrease in the accumulated substrate in affected tissues. Preclinical work conducted by Amicus’ Science team has demonstrated that pharmacological chaperones have a similar effect on recombinant enzymes, or those manufactured as enzyme replacement therapy, in rats and mice.

Co-administration of ERT and Pharmacological Chaperone Pre-clinical Data

In the case of co-administration therapy, preclinical data in mouse and rat models have shown increased stability and rhGAA (ERT) activity in key muscle tissues along with increased glycogen reduction. Preclinical data suggest that when compared to ERT alone, co-administration therapy may lead to increased cell/tissue activity, reduced dose or infusion frequency, reduced antibodies, and reduced allergic reactions. (These data were presented at the 2010 Annual Meeting of the American College of Medical Genetics and at the 6th Annual WORLD Symposium 2010.)

Preclinical work has been performed in separate experiments with each of the three different pharmacological chaperone molecules for Pompe, Fabry and Gaucher diseases and the respective ERTs, resulting in consistent findings.

Therefore, Amicus is advancing its co-administration effort into Phase 2 clinical studies in both Pompe and Fabry disease. The Fabry co-administration study began in the spring of 2011 and continues to enroll participants.

AT2220-010 Co-administration Study Design

The Pompe AT2220-010 Study will have three purposes:
- evaluate the safety of multiple doses of AT2220 administered before an ERT infusion;
- compare rhGAA enzyme activity levels and protein levels in the blood with and without co-administration with ERT;
- and evaluate the concentration of AT2220 in skeletal muscle one week after the oral dose in combination with ERT.

There will be an estimated 16 participants in this study, each receiving only one oral dose of AT2220 before one regularly scheduled ERT infusion. Each individual’s total participation in the study may last approximately three months. There will be 4 patient cohorts, each with an increasing dose of AT2220.

This is an international study that will enroll participants at a variety of sites. Males and females with Pompe disease, ages 18-65, on a stable regimen and dose of either Lumizyme or Myozyme may be eligible for participation. For more information, including more detailed inclusion criteria, please speak to your healthcare provider, visit www.clinicaltrials.gov keyword search AT2220-010, where the listing of study sites is regularly updated, or email clinicaltrials@amicustherapeutics.com.