Amicus Therapeutics, a biopharmaceutical company, has completed enrollment of 67 patients in the first phase III global registration study (Study 011) of migalastat HCl for fabry disease. Based on the timing of this milestone, Amicus and its collaborator GlaxoSmithKline (GSK) anticipate Study 011 results in the third quarter of 2012.

According to the company release, final enrollment of 67 patients exceeds initial target of 60 patients — results anticipated in 3Q12; as of December 2011, 21 of 23 patients who have completed the six-month treatment and six-month follow-up periods are currently enrolled in the ongoing phase 3 extension study and patient demographics to be featured at scientific congress in 1Q12.

John F Crowley, chairman and chief executive officer of Amicus Therapeutics stated, “The completion of enrollment in study 011 is a major accomplishment for Amicus, GSK and all those who have been involved in our Fabry program over the last several years. We believe this phase III study will be well-positioned to support a US marketing application for migalastat HCl, and we look forward to announcing results in the third quarter of next year.”

Study 011 is a six-month, placebo-controlled global phase III study of migalastat HCl for Fabry disease to support marketing applications for the US Food and Drug Administration (FDA) and other regulatory agencies. In September 2009, the first patient was randomized in Study 011 to receive migalastat HCl 150 mg or placebo on an every-other-day (QOD) oral dosing schedule for a six-month double-blinded treatment period. During a six-month open-label follow up period, patients continue treatment with migalastat HCl or switch from placebo to migalastat HCl. As of December 2011, 21 of 23 patients who have completed the six-month treatment and six-month follow-up periods are currently enrolled in the ongoing phase III extension study and remain on migalastat HCl treatment.

The primary efficacy endpoint for Study 011 is a change in interstitial capillary globotriaosylceramide (GL-3) as measured by kidney biopsy. Patients in Study 011 with a reduction of GL-3 deposits per capillary of at least 50% at six months will be considered responders. The final analysis will compare the number of responders in the migalastat HCl group vs. the placebo group. Amicus and GSK will utilize the Barisoni Lipid Inclusions Scoring System (BLISS) for the histological evaluation of GL-3 in the kidney biopsies. A manuscript on the BLISS methodology is currently in press and will be published in an upcoming issue of Archives of Pathology & Laboratory Medicine.

Secondary endpoints for Study 011 include safety and tolerability, urine GL-3, renal function, and quality of life (QOL). Urine GL-3 will be analyzed using the first analytically validated GLP assay, which was developed by Amicus to measure forms of GL-3 found in kidney cells. Renal function will be assessed by measuring iohexol glomerular filtration rate (GFR), eGFR, and 24-hour urine protein.

Amicus Therapeutics is a biopharmaceutical company at the forefront of developing therapies for rare diseases. The company 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 neurodegeneration.

Migalastat HCI is an investigational oral pharmacological chaperone in phase III development for the treatment of Fabry disease being developed in collaboration with GlaxoSmithKline PLC (GSK). Under the terms of the collaboration, GSK has an exclusive worldwide license to develop, manufacture and commercialize migalastat HCl. Amicus and GSK are conducting two phase III global registration studies (Study 011 and Study 012) of migalastat HCl monotherapy, along with a phase II study (Study 013) evaluating migalastat co-adminstered with enzyme replacement therapy (ERT) for the treatment of fabry disease.

Fabry disease is an inherited lysosomal storage disease and 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 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 disorders and stroke.