Amicus Therapeutics (FOLD) Ticks Lower on Following Study Results

February 15, 2013 10:41 AM EST
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Amicus Therapeutics (Nasdaq: FOLD), today announced additional 6-month (Stage 1) results from the first ongoing Phase 3 global registration study (Study 011) of investigational oral migalastat HCl monotherapy (150 mg, every-other-day) in males and females with Fabry disease who had genetic mutations identified as amenable to migalastat HCl in a cell-based assay. Stage 1 results were highlighted in an oral platform presentation1 at the Lysosomal Disease Network WORLD Symposium (LDN WORLD) by Dr. Fatih Ezgu, Gazi University.

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:

Post-Hoc Subgroup Analysis of Primary Endpoint (modified intent-to-treat (mITT), n=60): in a post-hoc sub-group analysis, patients with a higher baseline disease burden (0.3 inclusions or more per interstitial capillary, n=25) were compared to those with a lower baseline disease burden (0.3 or fewer inclusions per interstitial capillary, n=35). In the 25 patients (14 males and 11 females) with higher baseline disease burden, 7/11 (64%) on migalastat HCl and 2/14 (14%) on placebo were classified as responders. Among the 35 patients (8 males and 27 females) with lower baseline disease burden, 6/19 (32%) on migalastat HCl and 7/16 (44%) on placebo were classified as responders.

Urine GL-3: The observed median reduction in urine GL-3 from baseline was 17% for placebo and 12% for migalastat. However due to unexpected variability in the pre-treatment urine GL-3 data (>1.6 fold difference between values at screening and baseline), any potential treatment effects on urine GL-3 cannot be determined.
Renal Function from Baseline to Month 6: Renal function remained stable and changes from baseline were similar in both treatment groups during stage 1. Themean (SD) increase in estimated glomerular filtration rate (eGFR) was 2.7 (15.1) mL/min/1.73m2 in the migalastat HCl group compared to a mean decrease of 2.4 (10.8) mL/min/1.73m2 in the placebo group. No clinically meaningful changes in proteinuria were observed, and iohexol GFR data are currently being analyzed.

Safety: During the first 6 months, no drug-related serious adverse events have been observed. No subjects discontinued migalastat HCl therapy due to a treatment emergent adverse event and the majority of adverse events in both treatment groups were mild in nature.

John F. Crowley, Chairman and Chief Executive Officer of Amicus, stated, "The 6-month results presented today at the WORLD Symposium support our commitment to the ongoing development of migalastat HCl monotherapy. We look forward to reporting the 12-month results from this study to add to the entirety of the data that the FDA has indicated would support a potential U.S. conditional approval."

Study 011 results from Stage 2 are anticipated in the second quarter of 2013. The U.S. Food and Drug Administration (FDA) has indicated that it will consider the entirety of the Stage 1 and Stage 2 efficacy and safety data from Study 011. A meeting with the agency is anticipated in mid-2013 to discuss the U.S. conditional approval pathway for migalastat HCl under subpart H.

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 December 2012.

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