Amicus shares jump on positive late-stage data for Fabry disease drug migalastat

Shares in Amicus Therapeutics surged as much as 52 percent Tuesday after the company reported positive data from a Phase III trial of its experimental Fabry disease drug migalastat. CEO John Crowley indicated that pending positive results from a second late-stage trial, the company plans "to meet with regulatory authorities to discuss these data and determine the fastest registration pathway for migalastat."

The company said Study 011, which enrolled 67 patients with Fabry disease who have alpha-Gal mutations that are considered amenable to chaperone monotherapy based on a cell-based assay, was designed to measure the reduction of kidney interstitial capillary globotriaosylceramide (GL-3) following treatment with migalastat. The trial began with a six-month placebo-controlled treatment period, after which all patients received migalastat for a further six months, followed by a 12-month extension phase. Secondary endpoints included the measure of clinical outcomes, including renal function.

Results at 12 months showed that participants who had switched to migalastat during the course of the trial achieved a significant reduction in kidney interstitial capillary GL-3, while a "reduction in disease substrate was also observed in plasma lyso-Gb3, another important biomarker of disease." Meanwhile, patients who remained on migalastat for one year showed a "durable reduction" in both kidney interstitial capillary GL-3 and in lyso-Gb3. The company added that kidney function remained stable over 18 to 24 months, and that migalastat was generally safe and well-tolerated.

Crowley stated that the results "met our pre-defined criteria for success in terms of substrate reduction at 12 months, as well as clinical measures of kidney function maintained out to 24 months." He added that the "data provide important validation that a small-molecule chaperone can restore the function of a patient's own enzyme in patients with amenable mutations, and that our pharmacogenomic assays can identify these patients." Further, Crowley suggested that "these results…offer the prospect of a new treatment option that differs from traditional enzyme replacement therapy (ERT)."

Amicus and former partner GlaxoSmithKline reported in 2012 that migalastat had failed to meet the original primary endpoint of responder analysis with a 50-percent GL-3 reduction threshold at six months. The UK drugmaker subsequently returned rights to migalastat, as well as a next-generation Fabry disease ERT, back to Amicus last November, after Amicus revealed it would delay seeking FDA approval of migalastat until the second half of 2014. Amicus said that based on feedback from the US regulator, it eventually revised its analysis to pre-specify the primary analysis at month 12 as the mean change in GL-3 in patients with amenable mutations in a human embryonic kidney cell-based assay.

In addition to Study 011, migalastat monotherapy is being investigated in Fabry patients with amenable mutations in late-stage Study 012, as well as in the extension trial, Study 041. Amicus said top-line results from Study 012, which will evaluate the glomerular filtration rate over 18 months of treatment with migalastat versus ERT, are anticipated in the third quarter.

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