Amicus sets sights on approval as rare disease pill clears Phase III

Amicus Therapeutics CEO John Crowley

Amicus Therapeutics ($FOLD) has come a long way in two years, shaking off a clinical misstep on the way to a second Phase III success for its rare disease treatment. Now the biotech is preparing to make its case to regulators, hoping to win approval for a new approach to Fabry disease.

Migalastat, the company's lead drug, is designed to unseat the standard-of-care enzyme-replacement therapies (ERTs) currently used to treat Fabry, which results from a deficiency of alpha-galactosidase A and often leads to renal failure and death. In Phase III results revealed Wednesday, the treatment met both of its co-primary endpoints by measuring up to Sanofi's ($SNY) Fabrazyme and Shire's ($SHPG) Replagal in two measures of kidney function.

That means patients can safely switch between the leading ERTs and migalastat, Amicus said, and the biotech is betting they'll want to. Unlike the bi-weekly infusions required with Fabrazyme and Replagal, Amicus' drug is an every-other-day pill, making it more convenient and likely bolstering patient adherence, CEO John Crowley said, which could affect efficacy.

The drug, tailored for the roughly 30% to 50% of Fabry patients who carry a specific cellular mutation, already came through in an earlier Phase III trial in which it beat out placebo in reducing a key biomarker. With both data sets in tow, Amicus is getting started on a European application for migalastat and gearing up for a fourth-quarter meeting with the FDA to determine the quickest path forward in the U.S.

Among the treatment's co-signers is Raphael Schiffmann, a Fabry expert who served as an investigator for migalastat, Fabrazyme and Replagal. The Baylor physician said in a statement that he would use Amicus' drug over ERTs to treat patients with the appropriate mutations.

The new optimism over migalastat's potential comes after a series of setbacks imperiled the drug's future. Two years ago, in the treatment's first late-stage study, it failed to beat placebo in reducing levels of the Fabry biomarker GL-3 at 6 months in a general population of patients with the disease, sending Amicus' shares crashing earthward. Months later, deep-pocketed partner GlaxoSmithKline ($GSK) handed back the rights to migalastat, leaving Amicus on its own to pick up the pieces.

And that's what the biotech did. After the drug missed statistical significance in the first 6 months of its study, Amicus held a meeting with the FDA to talk about how it would analyze the then-blinded 12-month data. The biotech discovered that mean change in GL-3, not baseline reduction, was a better measure of effect on Fabry, and the agency agreed, also signing off on looking solely at patients with the aforementioned mutations

So, when those 12-month results became public in April, migalastat had gone from a questionable bet to a promising candidate, hitting its primary goals with durable cuts in GL-3. And now, with a second Phase III victory in the bag, the drug has become "a great lesson in persistence," Crowley said.

"The hardest thing in drug development is knowing when to quit, when to give up," he told FierceBiotech. "It's against our nature as biotech entrepreneurs, but sometimes you have to. And we came close last year."

With GSK in the rear-view, Amicus plans to launch and market migalastat on its own, keeping an ear open to new partnerships but maintaining that "our bar is quite high," Crowley said.

Beyond its lead candidate, the biotech is at work on a next-generation treatment that combines enzyme replacement with the chaperone technology at play in migalastat, nearing the clinic with a therapy that could make a difference for the patients not eligible for its other Fabry drug.

"Ultimately, our vision is that over the next several years every patient in the world with Fabry will take only an Amicus product," Crowley said, using companion diagnostics to determine which treatment is right for which person.

- read the results