Amicus Therapeutics Files for FDA Approval of Migalastat to Treat Fabry Disease

Amicus Therapeutics recently submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for its investigational oral medicine migalastat for treatment of patients 16 years and older with Fabry disease who have so-called “amenable” mutations.

The NDA seeks migalastat’s approval in the U.S. as an alternative to intravenous enzyme replacement therapy.

The application is supported by data from Phase 3 pivotal studies, including the FACETS trial (NCT00925301) in patients who had not received enzyme replacement therapy, a follow-up open-label study (NCT01458119), and the ATTRACT study (NCT01218659) in patients who previously had received enzyme replacement therapy.

In Fabry disease, the defective alpha-galactosidase A enzyme leads to buildup of globotriaosylceramide (GL3) lipids throughout the body, including in the cells of the kidney. Migalastat works by stabilizing specific mutant forms of the alpha-galactosidase enzyme in patients carrying so-called amenable mutations in the GLA gene.

Amenable mutations refer to the classification of more than 1,000 known GLA mutations as “amenable” or “not amenable” to treatment with migalastat. Patients with amenable mutations account for 35% to 50% of Fabry patients worldwide.

In the FACETS study, researchers randomized 67 patients to either a placebo group or the migalastat group, in which the therapy’s safety and effectiveness were assessed after six months of treatment. In a second stage of the study, patients received open-label treatment with migalastat for six to 12 months. Those who completed both stages were allowed to participate in an extension study with an additional year of treatment.

The ATTRACT study enrolled 57 patients with amenable GLA mutations who had enzyme replacement therapy for at least 12 months. Researchers randomized patients to either migalastat or current standard-of-care enzyme replacement therapy with Fabrazyme (agalsidase beta) or Replagal (agalsidase alfa) for 18 months, to evaluate the treatments’ safety and effectiveness.

One of the main goals of the trials was to assess renal function following treatment according to the iohexol Glomerular Filtration Rate.

The results of the FACETS study and its open-label extension were published in The New England Journal of Medicine in a study titled, “Treatment of Fabry’s Disease with the Pharmacologic Chaperone Migalastat.”

While an initial analysis showed no difference between migalastat and placebo, a follow-up review found evidence of “a significant and durable reduction in kidney GL-3 levels,” researchers wrote.

The results of the ATTRACT study showed that migalastat and enzyme replacement therapy had comparable effects on renal function. Complete results were published in the Journal of Medical Genetics in a study titled, “Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study.”

In 2016, the European Commission approved oral migalastat as a first-line therapy for the long-term treatment of Fabry disease in patients 16 and older with amenable mutations. The therapy is sold there under the brand name Galafold. Migalastat also is approved in Switzerland, Israel, Australia, and Canada.

In the U.S., the FDA previously had granted migalastat orphan drug and fast track designations.

“Today marks the very first Amicus submission of a new drug application to the U.S. FDA. This important milestone is the culmination of a strong collaboration and commitment among the patients, physicians and Amicus employees who have spent more than a decade to advance migalastat,” John F. Crowley, chairman and chief executive officer of Amicus Therapeutics, said in a press release.

“On the heels of our initial launch success for migalastat in Europe, our goal is to further expand access for more Fabry patients with amenable mutations in the U.S., Japan and other global geographies. We look forward to working with the FDA during the review process and to a potential U.S. approval of migalastat in 2018,” he added.

Fabry disease affects about 3,000 patients in the U.S., the country with the greatest prevalence of the disease.