Amicus Therapeutics Inc.'s shares (NASDAQ:FOLD) rocketed 20.4 percent Wednesday as the company delivered positive top-line data from a second phase III study of migalastat, its oral small-molecule chaperone for Fabry disease patients with a genetic mutation making them amenable to treatment.

The stock closed at $5.50, up 93 cents.

Patients taking the drug as a monotherapy met both of the study's primary endpoints on two key measures of kidney function, results that proved migalastat comparable to other enzyme replacement therapies (ERTs) and positioned Amicus to move ahead with European registration and prepare to meet FDA regulators ahead of submitting a new drug application.

"We feel very strongly that the totality of the data of these two phase IIIs, the largest ever done in Fabry's disease, will be strongly supportive of a filing in the U.S.," John Crowley, CEO of the Cranbury, N.J.-based company, told BioWorld Today.

Of the 5,000 to 10,000 people with Fabry disease, a rare inherited lysosomal storage disorder, about 30 percent to half have mutations that make them amenable to treatment with migalastat alone. For those patients, migalastat essentially binds to and stabilizes an enzyme which, when degraded without treatment in Fabry patients, leaves them insufficiently able break down lipids, which can lead to kidney damage and even kidney failure.

Results of the 18-month randomized, open-label trial showed that migalastat had a comparable effect to standard-of-care infused ERTs Fabrazyme (agalsidase beta, Sanofi SA) and Replagal (agalsidase alpha, Shire plc) on patients' kidney function as measured by the change in estimated glomerular filtration rate (GFR) and measured GFR. Migalastat also maintained levels of lyso-Gb3, an important biomarker of disease, in the plasma of patients who switched from ERT to migalastat.

A total of 60 males and females with Fabry and genetic mutations identified as amenable to migalastat monotherapy were randomized 1.5-to-1 to switch to migalastat or remain on ERT. All the subjects had received ERT infusions for at least 12 months (at least three months at the labeled dose) prior to entering the study.

"We think today's data strongly support the idea that migalastat is a clinically effective and approvable Fabry disease therapy that may have as much benefit on renal function as gold standard ERT," Cowen and Co. analyst Ritu Baral wrote in a note to investors.

Migalastat's performance vindicates Amicus' belief in the monotherapy, following London-based Glaxosmithkline plc's November 2013 decision to take a more passive role in the drug's development.

While GSK retains a nearly 15 percent equity stake in Amicus, it returned global rights to develop and commercialize migalastat in favor of receiving royalties and milestones on sales of both the monotherapy and a planned migalastat-ERT combination in several markets outside the U.S.

The new data extend results showing migalastat is generally safe and well tolerated by Fabry patients, giving it a profile that "will be a factor that will figure well into the benefit-risk assessment that regulators will take when reviewing the data for migalastat," said Amicus' chief medical officer, Jay Barth.

A total of 143 patients with Fabry disease have taken migalastat to date, some for more than eight years, he said. Of those, 96 percent have chosen to continue taking the drug when offered an extension study. There are now 97 patients taking migalastat as their only specific therapy for Fabry disease, he said.

The trial follows the company's first phase III, study 011, which was designed to measure the reduction of disease substrate (globotriaosylceramide, or GL-3) after migalastat therapy. Patients who switched from a placebo to migalastat after six months in that study showed a statistically significant reduction in kidney interstitial capillary GL-3 at month 12 (p = 0.013), and those who stayed on migalastat for 12 months showed a durable reduction in kidney interstitial capillary GL-3. (See BioWorld Today, April 30, 2014.)

Amicus has started work on a centralized procedure in Europe for a marketing authorization application (MAA) submission. The company has an MAA pre-submission meeting planned for the fourth quarter of this year. The MAA will be based primarily on comparability to ERT, with supportive data from study 011 and clinical data from other studies the company has collected over time, the company said.

In the U.S., Amicus is planning to present all its data from studies 012 and 011 with long-term data from all the extension studies in a pre-new drug application (NDA) meeting in which it will explore options for expediting its NDA. The agency had asked to see the all the data from studies 011 and 012 before reviewing an application, something Amicus can now deliver.

Amicus' big-picture plan is to advance its own ERT, AT-B100 (also known as JR-051), a recombinant human alpha-Gal enzyme, co-formulated with migalastat.

"Our vision is that over the next several years that patients and physicians will have the option to take either a monotherapy for those with amenable mutations or a next-generation enzyme replacement for those with non-amenable," Crowley said.

In published preclinical studies, migalastat in combination with currently approved Fabry ERTs led to stabilization of the enzyme in the circulation, and increased uptake of the active enzyme into key organs of disease compared to ERT alone.

Building on assets it acquired with last year's purchase of Callidus Biopharma Inc., the company is also advancing ERTs for Pompe, mucopolysaccharidosis type I and Gaucher diseases.