GlaxoSmithKline (GSK) and Amicus Therapeutics announced the first patient has commenced dosing in a phase III global registration study (Study 012) to compare the safety and efficacy of Amigal (migalastat HCl) and Enzyme Replacement Therapy (ERT) for the treatment of Fabry disease. The randomised, open-label, 18-month study will provide longer-term clinical data comparing migalastat HCl to ERT in patients with Fabry disease, a rare inherited lysosomal storage disorder.
GSK and Amicus are targeting up to 50 sites globally to enrol approximately 50 male and female Fabry patients who are currently receiving ERT treatment, and who have a genetic mutation that may be addressable with migalastat HCI. The primary outcome of efficacy will be renal function as measured by Glomerular Filtration Rate (GFR).
John F. Crowley, chairman and chief executive officer of Amicus, stated, “In collaboration with GSK we are pleased to announce the dosing of the first patient in Study 012, the first phase III pivotal study to compare Amigal to ERT. This is an important step in our clinical development plan and builds on the latest encouraging safety and renal function data from our ongoing Phase II extension study.”
Study 012 is the second of two phase III studies intended to support the worldwide registration of migalastat HCl for Fabry disease. Amicus and GSK are also conducting a six-month, placebo-controlled Phase III study (Study 011) of migalastat HCI at 37 sites worldwide to support marketing applications for the US Food and Drug Administration (FDA) and other regulatory agencies.
“We believe Amigal has the potential to provide an important treatment option in Fabry disease,” said Dr Philippe Monteyne, Head of Development and Chief Medical Officer for GSK Rare Diseases. “We are delighted with the progress that the joint Amicus-GSK team has made to advance the clinical development program since we entered an alliance in October 2010.”
Study 012 is a randomised, open-label, 18-month phase III study to compare the safety and efficacy of migalastat HCI (AT1001/GR181314A), and ERT in male and female patients with Fabry disease. The study was recently amended to randomise approximately 50 patients (30 to switch to migalastat HCl and 20 to remain on ERT). Eligible patients will have a genetic mutation that may be addressable with migalastat HCI.
Subjects who have been treated with either of the ERT preparations currently marketed, for at least 12 months, will be randomised on a 1.5:1 ratio to stop ERT and begin migalastat HCI treatment, or to continue receiving ERT treatment alone. Subjects in the migalastat HCI treatment arm will receive 150 mg of migalastat HCI every other day. Subjects in the ERT alone arm will continue on their current dose and regimen of ERT.
The primary outcome of efficacy will be renal function as measured by glomerular filtration rate (GFR) for the migalastat HCl and ERT groups at 18 months The primary analysis will use descriptive statistics to compare the mean changes in GFR for each arm. Secondary outcomes of efficacy include renal function as measured by 24-hour urine protein and other clinical outcomes.
Migalastat HCI is an orally-administered pharmacological chaperone in Phase III development for the treatment of Fabry disease. It has not been approved or licensed anywhere in the world. On October 29, 2010, Amicus announced a definitive agreement with Glaxo Group Limited (GSK) to develop and commercialise migalastat HCl. Under the terms of the agreement, GSK received an exclusive worldwide license to develop, manufacture and commercialise migalastat HCl.
In addition to the phase III monotherapy studies (Study 011 and Study 012), Amicus and GSK are currently conducting a Phase II clinical study to evaluate migalastat HCI co-administered with ERT for the treatment of Fabry disease.
Fabry disease is an inherited lysosomal storage disorder that is estimated to affect approximately 5,000 to 10,000 people worldwide. Fabry disease is 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 kidneys, central nervous system, heart, 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.
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