The first study, Study 011 (FACETS), was a Phase 3 study measuring the reduction of disease substrate (globotriaosylceramide, or GL-3) in Fabry patients with amenable mutations after treatment with migalastat. The study also evaluated clinical outcomes such as renal function and left ventricular mass index (LVMi) as secondary endpoints. Patients enrolled in this study were treatment-naïve or had not received enzyme replacement therapy for at least six months prior to joining the study. In Study 011, the recent data reported improvements in gastrointestinal symptoms, including a significant decrease in diarrhea in patients receiving migalastat vs. placebo, and after 18 to 24 months of treatment with migalastat, significant improvements in diarrhea and indigestion were seen, as well as promising trends in reflex and constipation.

 

Study 012 (ATTRACT) was a Phase 3, open-label study comparing oral migalastat to standard-of-care enzyme replacement therapies for Fabry disease (Fabrazyme and Replagal). Patients in this study had Fabry disease with amenable mutations in a clinical trial assay and had been treated with enzyme replacement therapy for a minimum of 12 months prior to joining the study. Co-primary outcome measures were mean annualized changes in estimated glomerular filtration rate (GFR) and measured (iohexol) GFR assessed by descriptive comparisons of migalastat and enzyme replacement therapy over 18 months. Secondary outcome measures featured LVMi and a composite of Fabry-associated clinical events (e.g. renal, cardiac or cerebrovascular). For the new Study 012 data, patient-reported outcome measures of pain and quality of life were reported, with measures of both remaining stable when patients switched from enzyme replacement therapy to migalastat.

 

“We are pleased to present compelling new data at WORLDSymposium on patient-reported outcomes on gastrointestinal symptoms, pain and quality of life from our Phase 3 studies. In addition to the previously reported migalastat Phase 3 data, it was also important to assess the impact of migalastat on some of the most commonly reported symptoms which can severely impact quality of life for people living with Fabry disease,” John F. Crowley, chairman and CEO of Amicus Therapeutics, said in a press release. “These positive results, shown for the first time today in both naïve and ERT switch patients, add to the totality of the data that suggest migalastat could be an important new therapy in the treatment of Fabry disease. These data also continue to show the positive effects for patients, owing, we believe, to migalastat's novel mechanism of action in all key organs and tissues of disease. We continue to move forward rapidly to seek regulatory approval.”

 

Previously reported Phase 3 data from both trials showed that migalastat treatment led to reductions in disease substrate, stability of kidney function and improvement in a key cardiac parameter in patients with amenable mutations. Amicus defines amenable mutations as having “an absolute increase of 3 percent of wild-type alpha-Gal A enzyme activity and a relative increase of 20 percent when exposed to migalastat in a cell-based in-vitro assay.” All patients in Study 011 and 012 presented with amenable mutations in the clinical trial HEK assay. After enrollment, Amicus developed a GLP HEK assay with a third party to measure the criteria for amenability with more quality control and rigor, and overall, based on results from mutations tested in that assay, the company believes approximately 30 to 50 percent of patients with Fabry disease have mutations amenable to migalastat.

 

Fabry disease, as defined by the Genetics Home Reference, a service of the U.S. National Library of Medicine, is “an inherited disorder that results from the buildup of a particular type of fat, called globotriaosylceramide, in the body's cells.” The disease is caused by mutations in the GLA gene, which provides genetic instructions for the production of alpha-galactosidase A, an enzyme that normally breaks down globotriaosylceramide. The mutations alter the structure and function of alpha-galactosidase A, preventing it from breaking down globotriaosylceramide, which then builds up in cells—particularly those lining blood vessels in the skin and cells in the kidneys, heart and nervous system—and damages them.