Amicus shares rally as a revised PhIII delivers positive Fabry data

Last fall, when GlaxoSmithKline ($GSK) decided to bail on Amicus Therapeutics and bowed out of their deal for the late-stage Fabry disease drug migalastat, some investors gave up on the company. After all, the drug had already failed the first step in the first of two Phase III studies, unable to provide a statistically significant improvement over a placebo arm.

Amicus CEO John Crowley

But Amicus CEO John Crowley didn't give up. After laying off staffers in a reorganization, investigators took a new tack in exploring the effect of their drug. And today investors rallied to the cause on Amicus' case that the drug looked positive at the 12-month and 24-month stage of treatment, driving up shares by more than 25%. The biotech says that the outcome sets the stage for a run at an approval, pending the results of another Phase III study.

Jitters about the company's future hit in late 2012 when Cranbury, NJ-based Amicus acknowledged that the drug did not significantly reduce the lipid substrate GL-3 that accumulates in the kidneys of Fabry patients suffering from an enzyme deficiency after the first 6-month leg of the 011 trial. Amicus then revised the statistical analysis plan to examine the "mean change in GL-3 in patients with amenable mutations." The key results:

Patients who switched from placebo to the drug after 6 months went on to demonstrate a statistically significant reduction in GL-3, says Amicus. The reduction was durable and investigators also tracked a durable response in what they called an important new biomarker for the disease, focusing on plasma lyso-Gb3.

Crowley told FierceBiotech last summer that he had hoped that the FDA would allow them to change the rules of the game, to let them review a follow-up 12-month response rate as a basis for an approval, with some added subgroup analysis to help illustrate the efficacy. The agency OK'd the design change but made it clear that the company still had a failure on its hands and avoided any commitment to using the 12-month data for an approval, forcing the company to wait for a late-2014 filing.

Now that it has gone the extra mile, the CEO says he's happy with the results.

"We are pleased to report that the 12 and 24 month results from Study 011 have 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," Crowley said in a release. "We believe these 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."

- here's the release