CRANBURY, NJ ( TheStreet) -- Amicus Therapeutics ( FOLD) CEO John Crowley came close to permanently shelving his company's experimental Fabry disease therapy following disappointing results from a late-stage study in December 2012 and the departure of partner GlaxoSmithKline ( GSK) about one year later. But Crowley -- famous for his perseverance -- decided to stick with the drug, migalastat, in the hope that a slower-to-enroll, second phase III study would resurrect chances for eventual approval.
Crowley made the right call. On Wednesday, Amicus announced results from the study demonstrating that Fabry patients taking currently available injectable drugs could switch successfully to migalastat, a pill taken every other day, and maintain kidney function required to keep the rare, inherited disease under control.
Based on the positive study results, Amicus intends to seek European approval for migalastat early next year. The company's U.S. filing plans are less clear. Amicus will schedule a meeting with FDA officials as soon as possible to determine if Wednesday's study results, plus data from the previous phase III study, are sufficient to seek migalastat approval here.
"We came very close to stopping development of migalastat, but we always believed patients were benefitting from the drug, so we tripled down on the program," said Crowley in a phone interview Tuesday night.
If approved, migalastat would be the first oral therapy for Fabry, giving it a significant convenience factor over Sanofi's ( SNY) Fabrazyme and Shire's ( SHPG) Replagal, both of which require bi-weekly intravenous infusions. Sales of Fabrazyme and Replagal, combined, total about $1 billion per year. Unlike its competition, Migalastat only works in Fabry patients with a specific genetic mutation, estimated to encompass between 30% and 50% of Fabry patients worldwide.
Amicus shares closed Tuesday night at $4.57.
Fabry is an inherited disease affecting about 10,000 people worldwide in which a genetic mutation stops an enzyme from breaking down a fatty substance known as globotriaosylceramide, or GL3. The buildup of GL3 in blood vessels throughout the body causes severe damage to kidneys, heart, brain, and other organ systems. Current Fabry treatments Fabrazyme and Replagal replace the patient's misshapen or missing native enzyme and clears GL3 from the body.
Amicus's migalastat takes a different approach to treating Fabry disease. The drug is a "chaperone" which accompanies, or fixes, a patient's native enzyme. Without the Amigal chaperone, the native enzyme in a Fabry patient doesn't work well and can't get to the place in a cell where it's needed to break down GL3. But with Amigal as a helper, the native enzyme is stabilized and has increased cellular activity so it can break down GL3. Migalastat doesn't work unless enough native enzyme is present, which is why Fabry patients with too little native enzyme or badly mutated enzyme don't benefit.
In the new phase III study, 60 Fabry patients with amenable mutations were treated for at least 12 months with either Fabrazyme or Replagal. Thirty-six patients were then switched to migalastat and the remaining 24 patients remained on their currently approved enzyme replacement therapy. The patients were followed for 18 months, after which two measures of kidney function -- estimated GFR and measured GFR -- found migalastat to be statistically equivalent to the enzyme replacement therapies, meeting the co-primary endpoints of the study.
In addition, levels of plasma lyso-Gb3, a biomarker used to assess Fabry progression, remained low and stable across both arms of the study.
Dr. Raphael Schiffmann of the Baylor Research Institute and an investigator in the study, said, in a statement: "I believe the results from Study 012 show a positive treatment effect of migalastat in Fabry patients with amenable mutations."
In December 2012, the first migalastat phase III study failed to achieve its primary endpoint of kidney response compared to a placebo, although the results trended strongly in migalastat's favor. Amicus dug deeper into the study and found some anomalies and data suggesting migalastat was benefiting Fabry patients, but FDA refused the company's request to change the statistical plan. In November 2013, GlaxoSmithKline returned all rights to migalastat to Amicus.
Amicus now owns 100% of the worldwide rights to migalastat, which in a year or so, could become the first oral treatment for Fabry ever approved.
Crowley's perseverance paid off.