Amicus, Glaxo Release Top-Line Six-Month Primary Treatment Period Results from First Phase 3 Fabry Monotherapy Study

Amicus Therapeutics

and GlaxoSmithKline plc

today announced the 6-month primary treatment period results from the first Phase 3 global registration study (Study 011) of investigational oral migalastat HCl monotherapy in males and females with Fabry disease who had genetic mutations identified as amenable to migalastat HCl in a cell-based assay. Study 011 randomized a total of 67 patients to receive oral migalastat HCl 150 mg or placebo on an every-other-day (QOD) dosing schedule during a 6-month, double-blind primary treatment period. Reduction of GL-3 Substrate in Kidney Interstitial Capillaries: Globotriaosylceramide (GL-3) is the lipid substrate that accumulates in tissues of patients with Fabry disease, most notably in the kidney. GL-3 clearance from the kidney interstitial capillaries has been used as a marker of treatment effect in Fabry disease. The pre-designated primary endpoint of Study 011 was a responder analysis evaluating the number of patients who demonstrated a 50% or greater reduction in kidney interstitial capillary GL-3 after 6 months of treatment with migalastat HCl compared to placebo. During a 6-month open label follow-up period all patients received migalastat HCl. The FDA has also indicated that it will consider the 12-month efficacy and safety data from Study 011. The paired kidney biopsies from baseline and month 6 were assessed by histological scoring using the published, quantitative Barisoni Lipid Inclusion Scoring System with Virtual Microscopy (BLISS-VM).^1 This methodology will also be utilized for the evaluation of the kidney biopsies at month 12. Amicus and GSK remain blinded to the 12-month data. In Study 011 patients with evaluable baseline biopsies, 13/32 (41%) in the migalastat HCl treatment group demonstrated a 50% or greater reduction in kidney interstitial capillary GL-3 after 6 months of study treatment versus 9/32 (28%) in the placebo group. This difference did not achieve statistical significance (p=0.3) according to the pre-specified primary endpoint analysis. In addition to the binary responder analysis reported above, a pre-specified secondary analysis assessing the absolute percent change in kidney interstitial capillary GL-3 from baseline to month 6 was performed. Taken alone this analysis showed a median reduction of 41% in the migalastat HCl group versus a median reduction of 6% in the placebo group (p=0.093). To date, no drug-related serious adverse events have been observed. The most common treatment emergent adverse events occurring in 10% or more of subjects were (migalastat; placebo, respectively): headache (35%; 21%); fatigue (12%; 12%); nausea (12%; 9%); nasopharyngitis, or inflammation of the nose and throat (15%; 6%); and parasthesia, or tingling sensation of the skin (9%; 12%). The 4 dropouts in this portion of the study were deemed by the investigators to be unrelated to study medication. The 6-month secondary endpoints in Study 011 continue to be analyzed and will be presented at the Lysosomal Disease Network WORLD Symposium (LDN WORLD), to be held February 12-15, 2013, in Orlando, Florida. Secondary endpoints include urine GL-3 and renal function (iohexol GFR, eGFR and 24-hour urine protein).