About a year after the outlook for speedy U.S. approval of Fabry disease drug migalastat turned from sunny to sober on FDA feedback, Amicus Therapeutics Inc. said new talks with the agency yielded a path to full approval built on gathering new gastrointestinal (GI) data in a study that won’t read out until 2019, likely pushing potential approval out to 2020.

Despite winning European approval for the molecular chaperone in May, the update dashed dreams of an accelerated U.S. review, sending company shares (NASDAQ:FOLD) 21.8 percent lower to $6.51 on Tuesday.

Armed with the confidence of having final written minutes of an in-person type B meeting in hand, Amicus said it expects full U.S. approval could require it to run a randomized, 12-month, placebo-controlled pivotal “crossover” study to measure diarrhea in treatment-naïve Fabry patients who have an amenable mutation and GI symptoms. The assessment will be formed based on established FDA irritable bowel syndrome guidance issued in May 2012.

It’s estimated that there are 10,000 people in the developed world with Fabry disease. More than half of them experience GI symptoms, including diarrhea, abdominal pain, constipation, nausea and vomiting.

The pivotal study, for which Amicus is working to finalize a protocol with the FDA, is expected to be sufficiently powered to generate the data the agency wants with about 35 patients. The company plans to initiate enrollment in 2017.

“The generation of the reflected GI data from FDA is acceptable to us for four primary reasons,” Amicus CEO John Crowley said during a conference call held to discuss the update. “One, the GI symptoms study has a high likelihood of success. Two, this is a feasible study in terms of patient recruitment. Three, this study can be conducted in a reasonable amount of time. And four, it is for full approval.”

Analysts gave the program’s chance of success mixed odds. Leerink Partners analyst Joseph Schwartz estimated a 33 percent probability for migalastat, in light of a tougher U.S. regulatory environment.

“Given the long road which lays ahead, we believe it makes sense to err on the side of caution until we gain more clarity on enrollment progress, study design/endpoints, and the attractiveness of the ultimate indication/label which may result,” he wrote.

Cowen and Co. analyst Ritu Baral was more optimistic. Though lowering Cowen’s price target for Amicus shares to $12 from a previous $15, she wrote that Cowen sees a good chance of success given prior GI data seen in the company’s phase III FACETS trial, also known as study 011. The largest phase III trial ever done in Fabry disease at the time, it showed a significant decrease in diarrhea (unadjusted p=0.03) in patients with amenable mutations treated with migalastat vs. placebo during the six-month double-blind phase. The decrease persisted after 18 months to 24 months of treatment with the drug. (See BioWorld Today, Oct. 5, 2015.)

In addition to starting to outline plans for the new study, the Cranbury, N.J.-based company said its conversation with the FDA covered access to migalastat for U.S. patients through an intermediate expanded access program. The program will allow those patients currently on enzyme replacement therapy who meet the requirements for expanded access use and who would not qualify for the GI study to remain on drug. Patients in the U.S. who are currently enrolled in Amicus’ ongoing long-term clinical extension study, some on treatment for more than 10 years, will also continue to have access to migalastat.

The European Commission approved migalastat, now marketed as Galafold, on May 30 as a first-line therapy for long-term treatment of adults and adolescents, 16 and older, with a confirmed diagnosis of Fabry disease. The label includes 313 GLA mutations that have been identified as amenable to treatment with the oral medicine, which represent between 35 percent and 50 percent of the currently diagnosed Fabry population. That approval rested primarily on the basis of FACETS and another phase III trial, called ATTRACT, also known as study 012. Amicus has since worked on launching it country-by-country in the EU, a task that will continue in 2017. (See BioWorld Today, June 8, 2016.)

While there are enzyme replacement therapies available for the treatment of Fabry disease, specifically Shire plc’s Replagal and Sanofi SA’s Fabrazyme, Galafold is the first oral treatment for the condition.