Amicus Therapeutics (Nasdaq: FOLD) today announced that additional positive data from the ongoing Phase 2 extension study of its investigational drug Amigal™ (migalastat HCl) for Fabry disease will be presented at the Lysosomal Disease Network WORLD Symposium in Las Vegas, Nevada, February 16-18th, 2011. In addition, the Company announced that it will present encouraging data from its preclinical studies evaluating the co-administration of pharmacological chaperones with enzyme replacement therapy (ERT) in Fabry disease, as well as from preclinical studies examining the use of pharmacological chaperones for the treatment of genetically defined subpopulations of Parkinson's disease and Alzheimer's disease.
Preliminary Data Update from Phase 2 Long-Term Extension Study of Migalastat HCl for Fabry Disease
Twenty-six subjects completed either 12 or 24 weeks of treatment with migalastat HCl during the initial Phase 2 studies and 23 subjects enrolled in a separate, long-term extension study designed to evaluate the long-term safety and efficacy of migalastat HCl. Over the course of the initial Phase 2 and extension studies, 15 subjects have been treated with migalastat HCl for more than 3 years and 7 subjects have been treated with migalastat HCl for more than 4 years. Seventeen subjects continue to receive treatment in the ongoing extension study.
During the course of the extension study, treatment with migalastat HCl has continued to be generally well tolerated, with no drug-related serious adverse events. The most common adverse events have been headache, arthralgia, diarrhea and fatigue.
Renal function continues to be evaluated by two measures in the extension study, estimated glomerular filtration rate (eGFR) and 24-hour urine protein. Preliminary data indicate that eGFR has remained stable out to 3-4 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 +1.6 mL/min/1.73m2. Additionally, reduced 24-hour urine protein continues to be observed in multiple subjects identified as responders to migalastat HCl, with a mean 21% and median 34% reduction from baseline in this group of subjects.
Co-administration with ERT in Fabry Disease and Pompe Disease
Amicus previously reported promising preclinical data demonstrating that the co-administration of a pharmacological chaperone with ERT has the potential to address key limitations of ERT. The addition of a pharmacological chaperone has been shown to prevent the loss of activity of ERT in the circulation, increase tissue uptake, and increase substrate reduction in multiple disease-relevant tissues. Preclinical proof of concept has been established for Fabry disease and Pompe disease.
The Company will present a review of new and historical data from preclinical studies of migalastat HCl co-administered with ERT in an animal model of Fabry disease. Amicus and its partner GlaxoSmithKline PLC (GSK) are sponsoring an ongoing Phase 2 study evaluating the co-administration of migalastat HCl with ERT for Fabry disease. Results from this study are expected in the second half of 2011.
In addition, Amicus will present pharmacokinetics and muscle distribution data from a Phase 1 study of AT2220 that support the planned Phase 2 clinical study of AT2220 co-administered with ERT in Pompe patients. The Company expects to initiate this study in the first half of 2011 and to report preliminary results in the second half of 2011. The Company intends to seek U.S. FDA approval to lift the current hold on the AT2220 program as part of its development plan.
Diseases of Neurodegeneration
Amicus is investigating the potential use of pharmacological chaperones for the treatment of genetically defined sub-populations of patients with Parkinson's disease and Alzheimer's disease. Amicus previously reported encouraging results from preclinical studies evaluating the use of a pharmacological chaperone for the treatment of Parkinson's disease. Amicus will present additional data from preclinical studies that evaluated the pharmacological chaperone AT2101 in mouse models of Parkinson's disease as well as data related to the properties of new compounds, including AT3375. In 2011, the Company expects to complete late-stage preclinical proof of concept studies, including IND-enabling activities, for AT3375. The Amicus Parkinson's Disease program is funded in part by a grant from The Michael J. Fox Foundation (MJFF).
Additionally, Amicus continues to advance its preclinical program evaluating a pharmacological chaperone approach for the treatment of Alzheimer's disease. The Company will present scientific data on the link between lysosomal dysfunction and neurodegeneration, including data related to a preclinical program evaluating a pharmacological chaperone approach for the treatment of Alzheimer's disease. The Company expects to continue preclinical proof of concept studies during 2011. The Amicus Alzheimer's Disease program is funded in part by a grant from the Alzheimer's Drug Discovery Foundation (ADDF).