Amicus, in collaboration with GlaxoSmithKline (GSK), is developing the investigational pharmacological chaperone migalastat HCl as a monotherapy and in combination with ERT for the treatment of Fabry disease. When co-administered with ERT, migalastat HCl binds to and stabilizes infused enzyme in the circulation.
Dr. Warnock said, "Migalastat HCl 150 mg co-administered with two different doses of Fabrazyme, as well as one dose of Replagal, appeared to increase enzyme activity compared to each of these ERTs alone. The use of a pharmacological chaperone to maintain infused alpha Gal-A enzymes in optimally active form represents a potential approach to managing ERT outcomes in patients with Fabry disease."
Results were presented for a total of 12 patients who received migalastat HCl 150 mg co-administered with ERT (Fabrazyme in 8 patients and Replagal in 4 patients). Each patient received their current dose and regimen of ERT at one infusion. A single oral dose of migalastat HCl 150 mg was co-administered two hours prior to the next infusion of the same ERT at the same dose and regimen. Due to the Fabrazyme supply difficulties during enrollment, 5 subjects had been receiving 0.5 mg/kg Fabrazyme infused every two weeks and 3 subjects had been receiving 1.0 mg/kg infused every four weeks. Four subjects were receiving Replagal 0.2 mg/kg every two weeks.
Preliminary Results - Migalastat HCl 150 mg Co-Administered with ERT (Fabrazyme and Replagal) (n=12)
Alpha-Gal A Levels of Active Enzyme in Plasma Area Under the Curve (AUC)
Migalastat HCl + ERT vs. ERT Alone
|Migalastat HCl Dose||ERT||Mean Fold-Increase vs. ERT Alone (Range)|
|4||150 mg||Replagal 0.2 mg/kg||4.4 (3.2 to 5.0)|
|5||150 mg||Fabrazyme 0.5 mg/kg||3.0 (2.0 to 4.2)|
|3||150 mg||Fabrazyme 1.0 mg/kg||2.0 (1.6 to 2.2)|
Alpha-Gal A Levels of Active Enzyme in Skin at Days 2 and 7
Migalastat HCl + ERT vs. ERT Alone
Mean Fold-Increase vs. ERT
Alone at Day 2 (Range)
Mean Fold-Increase vs. ERT
Alone at Day 7 (Range)
|4||150 mg||Replagal 0.2 mg/kg||1.8 (1.4 to 2.3)||1.4 (1.1 to 1.8)|
|5||150 mg||Fabrazyme 0.5 mg/kg||2.6 (1.1 to 3.9)||1.4 (0.7 to 2.8)|
|3||150 mg||Fabrazyme 1.0 mg/kg||1.9 (1.6 to 2.1)||1.4 (1.2 to 1.7)|
About Study 013
Study 013 is an open-label Phase 2 drug-drug interaction study to evaluate the safety and pharmacokinetic (PK) effects a single oral dose of migalastat HCl (150 mg or 450 mg) co-administered with ERT (Fabrazyme® or Replagal®). Study 013 completed enrollment of 23 males with Fabry disease who are currently on ERT. Each patient receives their regular dose and regimen of ERT. A single oral dose of migalastat HCl is co-administered 2 hours prior to the next ERT infusion.
Enzyme activity is being measured in plasma (total area under the curve, or AUC) during each infusion and in tissue (skin) following each infusion. In published preclinical studies1 migalastat HCl co-administered with ERT in Fabry knock-out mice increased active enzyme in plasma and enzyme uptake into skin, which led to further reductions in globotriaosylceramide (GL-3) compared to ERT alone. For people living with Fabry disease, deficient alpha-Gal A enzyme activity leads to the accumulation of globotriaosylceramide (GL-3) in tissues affected by disease, including the kidney, heart and skin.
About Migalastat HCl
Amicus in collaboration with GlaxoSmithKline (GSK) is developing the investigational pharmacological chaperone migalastat HCl for the treatment of Fabry disease. Amicus has commercial rights to all Fabry products in
As a monotherapy, migalastat HCl is designed to bind to and stabilize, or "chaperone" a patient's own alpha-galactosidase A (alpha-Gal A) enzyme in patients with genetic mutations that are amenable to this chaperone in a cell-based assay. Migalastat HCl monotherapy is in Phase 3 development (Study 011 and Study 012) for Fabry patients with genetic mutations that are amenable to this chaperone monotherapy in a cell-based assay. Study 011 is a placebo-controlled study intended primarily to support U.S. registration, and Study 012 compares migalastat HCl to ERT to primarily support global registration.
For patients currently receiving ERT for Fabry disease, migalastat HCl in combination with ERT may improve ERT outcomes by keeping the infused alpha-Gal A enzyme in its properly folded and active form.
Migalastat HCl co-administered with ERT is in Phase 2 (Study 013) and migalastat HCl co-formulated with
About Fabry Disease
Fabry disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called alpha-galactosidase A (alpha-Gal A). The role of alpha-Gal A within the body is to break down specific lipids in lysosomes, including globotriaosylceramide (GL-3, also known as Gb3). Lipids that can be degraded by the action of α-Gal are called "substrates" of the enzyme. Reduced or absent levels of alpha-Gal A activity leads to the accumulation of GL-3 in the affected tissues, including the kidneys, heart, central nervous system, 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.
It is currently estimated that Fabry disease affects approximately 5,000 to 10,000 people worldwide. However, several literature reports suggest that Fabry disease may be significantly under diagnosed, and the prevalence of the disease may be much higher.
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could be delayed because we identify serious side effects or other safety issues; the potential that we will need additional funding to complete all of our studies and, our dependence on third parties in the conduct of our clinical studies. Further, the results of earlier preclinical studies and/or clinical trials may not be predictive of future results. In addition, all forward looking statements are subject to other risks detailed in our Quarterly Report on Form 10-Q for the quarter ended
Sara Pellegrinospellegrino@amicusrx.com (609) 662-5044
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