Amigal migalastat: Additional Phase III data

Amicus reported data from 17 patients with amenable genetic mutations as determined by a good laboratory practice (GLP)-validated human embryonic kidney (HEK) cell-based in vitro assay who crossed over from placebo at month 6 to receive 150 mg oral Amigal every other day in the open-label stage 2 of the double-blind, international Phase III FACETS (Study 011) trial. Amigal met the stage 2 primary endpoint of reducing the mean number of GL3 inclusions per capillary as assessed by histology in kidney biopsies at month 12 compared to month 6 (reduction of 0.31 inclusions per capillary, p=0.013). Amenable mutations were defined as having an absolute increase of 3% of wild-type alpha galactosidase A activity and a relative increase of 20% when exposed to Amigal in a cell-based in vitro assay.

In 2012, Amicus reported data from stage 1 of the trial showing that Amigal missed the primary endpoint of improving the proportion of patients with a >=50% reduction in kidney interstitial capillary GL-3 levels as measured in kidney biopsies from baseline to 6 months vs. placebo (41% vs. 28%, p=0.3) (see BioCentury, Dec. 24, 2012 & Feb. 18, 2013). Amicus said the variability and low levels of GL-3 at baseline contributed to a "higher-than-anticipated" placebo response at month 6. The company subsequently identified the mean change in GL-3 "as a more appropriate way to control for the variability in GL-3 levels." A post hoc analysis of patients with HEK amenable mutations in stage 1 of the trial showed that Amigal significantly reduced the mean number of GL-3 inclusions per capillary from baseline to month 6 vs. placebo (reduction of 0.25 inclusions per capillary, p=0.008). Amicus said the reduction was durable through month 12 in patients who received Amigal for 12 months (n=22). ...