- Amicus Therapeutics on Friday won an accelerated U.S. approval of its Fabry disease drug Galafold, giving patients with the rare genetic disorder a new treatment option for the first time in over a decade. On Monday, the company said the new product comes at an average list price of $315,000 per year in the U.S.
- The Food and Drug Administration's OK comes about one year after the agency dropped a requirement for further study of the drug, reversing a 2016 decision that would have substantially delayed when Amicus could have submitted Galafold for approval.
- In an interview, company CEO John Crowley pointed to passage of the 21st Century Cures Act and a re-engagement with regulators as key turning points in getting Galafold back on track in the U.S. Critics, however, question whether the FDA's acceptance of Galafold's application pushes regulatory flexibility too far.
Fabry disease, one of 50 or so lysosomal disorders, is caused by a defect in a gene known as GLA, which triggers buildup of a type of fat in blood vessels and other organs. Over time, that fat buildup can cause kidney disease, stroke, abnormal heart rhythms and early death.
Current treatment is limited to an enzyme replacement therapy sold by Sanofi under the brand name Fabrazyme (agalsidase beta). Patients are infused with the drug every two weeks to reduce fat deposits in the kidneys. Sanofi noted in an email to BioPharma Dive that, in the U.S., the average annual cost of Fabrazyme per patient is approximately $290,000 based on average patient dose — which is tied to patient weight — and adherence.
Galafold (migalastat), on the other hand, is an oral drug designed to help boost the activity of an enzyme that's rendered dysfunctional in Fabry patients. Likened to a "chaperone," Galafold was shown in a clinical trial to be more effective than placebo in clearing deposits of the problematic fat, called GL-3, in blood vessels of the kidney.
That evidence, along with results from patients switching off of enzyme replacement therapy, was enough for regulators in the EU.
But when Amicus approached the FDA in 2016, the agency said it would need an additional 12-month, placebo-controlled study in Fabry patients who hadn't been treated before, focusing in particular on gastrointestinal (GI) symptoms.
The request was a major setback, delaying submission and hurting Amicus' chances of speedily bringing Galafold to market in the U.S.
When Amicus looked at the feasibility of doing the study, however, the company estimated enrolling the 35 patients needed could take between five to seven years. The problem, Amicus' Crowley said, was finding patients who had mutations amenable to treatment, hadn't received enzyme replacement therapy in the past and presented GI symptoms.
But, invigorated by the passage of the 21st Century Cures Act, which encourages more collection of patient input and real-world data, Amicus tried again with the FDA.
And in a surprise, the FDA agreed to drop its prior request and gave Amicus a green light to file Galafold for approval.
Crowley pointed to the FDA's reevaluation of longer-term data, as well as its solicitation of patient input outside of Amicus, as evidence of the impact of the legislation.
"That's the world that we need to evolve to. I think it's so incredibly important for the regulators [to be] able to apply the highest regulatory science — the gold standard for safety and efficacy — but being able to evaluate that in the context of each new medicine and each disease," Crowley said.
Critics, though, noted Crowley's former business ties to FDA Commissioner Scott Gottlieb, who has supported greater flexibility in drug approvals. In addition to the rethink on Galafold, the FDA has shown itself willing to relax demands for additional data from Eli Lilly & Co. and TherapeuticsMD.
Galafold isn't approved for all individuals with Fabry, only those patients with one of some 348 mutations of the GLA gene amenable to treatment. Amicus estimates there are about 3,000 patients in the U.S. with Fabry, as many as half of whom could have one of those targeted mutations. The drug is already approved in the EU, Japan and five other countries.
Due to Galafold being approved under an accelerated approval pathway, Amicus will conduct a Phase 4 confirmatory study to further characterize Galafold's efficacy and safety.
The company will begin shipping Galafold to a limited distribution network within a week, but has not yet announced a price. A conference call to discuss the FDA approval is currently set for Monday.