Amicus Therapeutics announced the dosing of the first subject in a phase II clinical trial designed to evaluate the co-administration of its investigational drug Amigal (migalastat hydrochloride) with Enzyme Replacement Therapy (ERT) for Fabry disease. This open-label phase II study is investigating drug-drug interactions between Amigal and the ERTs Fabrazyme and Replagal.

Preclinical studies have demonstrated that co-administration of Amigal results in a prolonged circulating half-life of ERT, increased enzyme activity in cells, and greater substrate reduction in target tissues compared to that seen with ERT alone. Amigal is being developed in collaboration with GlaxoSmithKline (GSK), as part of an alliance between GSK rare diseases and Amicus.

John F. Crowley, chairman and CEO of Amicus, stated “The commencement of this clinical study is an important milestone for Amicus and for pharmacological chaperone technology. Based on encouraging preclinical results we believe the co-administration of Amigal with ERT has the potential to provide significant benefit for people with Fabry disease. The advancement of this approach is a part of our vision to provide two new treatment options for Fabry patients in the future—Amigal as a monotherapy or Amigal co-administered with ERT. Finally, we also believe this study will provide us with valuable proof of concept for applying this approach to other lysosomal storage diseases and more broadly to other indications treated with therapeutic proteins.”

The phase II trial will evaluate the safety and pharmacokinetics of Amigal and ERT when co-administered in 18 male patients with Fabry disease, ages 18-65, who have been receiving ERT for at least one month before study entry. Patients enrolled in this study need not have a genetic mutation responsive to Amigal as a monotherapy. Each patient will receive ERT alone and then ERT after administration of a single oral dose of Amigal. There will be two cohorts of nine patients treated with one of two Amigal dose levels.

The primary outcome measure will be a comparison of the ERT activity in plasma and safety and tolerance with and without co-administration of Amigal. The effect of co-administration of ERT on the pharmacokinetics and safety of Amigal will also be evaluated.

A secondary outcome measure includes distribution of the ERT to skin. Other outcome measures include evaluating the effect of co-administration of Amigal and ERT on GL-3 levels in skin and GL-3 excretion in urine. Amicus expects results from this study to be available in the second half of 2011. Approximately five clinical sites will participate in this trial in the United States and in Europe.

On October 29, 2010, Amicus announced a definitive agreement with GSK to develop and commercialize Amigal (migalastat HCl), currently in phase III, for the treatment of Fabry disease as a monotherapy. Under the terms of the agreement, GSK received an exclusive worldwide license to develop, manufacture and commercialize migalastat HCl. As part of the agreement, GSK and Amicus also intend to investigate Amigal as a potential treatment for Fabry disease when co-administered with ERT.

The phase III study (Study 011) of migalastat HCl is ongoing and patients are being enrolled at 36 investigational sites worldwide. A majority of the planned 60 patients have been enrolled in the study. The Company expects to complete enrollment in the first half of 2011 and to report top line results from this study in the second half of 2011.

Amicus and GSK intend to commence an additional phase III study (Study 012) in the first quarter of 2011. Study 012 will be an 18-month, randomized, open-label study comparing migalastat HCl to Enzyme Replacement Therapy (ERT) in approximately 60 subjects. The primary outcome of efficacy will be renal function as measured by Glomerular Filtration Rate (GFR).

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 a complex lipid called GLobotriaosylceramide (GL-3). Reduced or absent levels of alpha-Gal A activity leads to the accumulation of GL-3 in the affected tissues, including the central nervous system, heart, kidneys, 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.

Amicus Therapeutics is a biopharmaceutical company focused on developing treatments for rare diseases and is developing orally-administered, small molecule drugs called pharmacological chaperones, a novel, first-in-class approach to treating a broad range of diseases including lysosomal storage disorders and diseases of neuro-degeneration.