Study 011 consists of a 6-month, double-blind period (Stage 1) when subjects received migalastat HCl 150 mg or placebo, a 6-month open label-follow up period (Stage 2) when all patients received migalastat HCl, and an ongoing 12-month open-label extension.
Initial top-line Stage 1 results previously reported in December, 2012 for the primary endpoint in Stage 1 did not meet statistical significance. The pre-specified primary and secondary analyses of the primary endpoint numerically favored migalastat HCl over placebo. In the primary responder analysis, 13/32 (41%) in the migalastat HCl group versus 9/32 (28%) in the placebo group demonstrated a 50% or greater reduction in kidney interstitial capillary GL-3 from baseline to month 6 (p=0.3). Taken alone the secondary analysis of the absolute percent change in kidney interstitial capillary GL-3 from baseline to month 6 showed a median reduction of 41% in the migalastat HCl group versus a median reduction of 6% in the placebo group (p=0.093).
Study 011 entry criteria, particularly elevated urine GL-3, were intended to enrich for patients with higher interstitial capillary GL-3, and more measurable disease burden. Although all patients had detectable interstitial capillary GL-3 at baseline, a number of patients had low levels of GL-3 at baseline, making it difficult to detect a significant difference in responders between the 2 treatment groups. Clearance of kidney interstitial capillary GL-3, a marker of treatment effect, is being measured by histology2 in evaluable kidney biopsies from baseline to month 6 (Stage 1) as well as baseline to month 12 (Stage 2). Stage 2 results remain blinded at this time.
Dr. Ezgu said, "The 6-month data from Study 011 are encouraging, including a post-hoc subgroup analysis presented today, and we continue to evaluate patients in this ongoing study. There is still an unmet medical need for Fabry disease treatments. Migalastat HCl may potentially offer an oral treatment for Fabry patients with amenable mutations based on these results from Study 011 and earlier clinical studies, and potentially forthcoming data from ongoing studies."
Study 011: Stage 1 (Baseline to Month 6) Updated Data Highlights at LDN WORLD Symposium:
Study 011 results from Stage 2 are anticipated in the second quarter of 2013.
A second Phase 3 global registration study (Study 012) is also underway to compare open-label migalastat HCl to ERT to primarily support global registration. Study 012 (The ATTRACT, or FAB-AT1001-012 Study) is a randomized, open-label 18-month Phase 3 study investigating the safety and efficacy of oral migalastat HCl 150 mg QOD compared to standard-of-care infused therapy using ERTs (Fabrazyme® and Replagal®). This study achieved final enrollment of 60 total patients in
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Study 011 Design
Study 011 - also referred to as FACETS - is one of 2 ongoing Phase 3 studies of migalastat HCl monotherapy being conducted by Amicus and GlaxoSmithKline (GSK). This study was designed based on feedback from the
The primary analysis compared the number of responders in the migalastat HCl versus placebo groups in Stage 1, based on a 50% or greater reduction in interstitial capillary globotriaosylceramide (GL-3) as measured in kidney biopsies. Pathologists blinded to biopsy sequence are using the published, quantitative Barisoni Lipid Inclusion Scoring System with virtual microscopy (BLISS-VM)2 for the histological evaluation of interstitial capillary GL-3 in kidney biopsies from baseline to month 6 (Stage 1) and from baseline to month 12 (Stage 2). Secondary endpoints for Study 011 include safety and tolerability, urine GL-3 and kidney function.
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
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 manifestations 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.
1. Nicholls, et al., Phase 3 Study of Migalastat HCl for Fabry Disease: Stage 1 Results, LDN WORLD 2013
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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
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