Migalastat is new treatment for a rare genetic disorder, Fabry disease

Migalastat is the first oral medicine for Fabry disease of adults that has been approved by the U.S. Food and Drug Administration in 15 years . Migalastat is a 123-mg capsule taken once every alternate day, at the same time of day.

In the United States, an estimated 3000 people have Fabry disease.It is a rare inherited X-linked lysosomal disorder caused by a deficiency of the enzyme α-galactosidase A (GLA) that results in buildup of a type of fat called globotriaosylceramide (GL-3) in blood vessels, the kidneys, the heart, the nerves and other organs.This deficiency leads to the buildup of globotriaosylceramide (GL-3) in blood vessels, kidneys, heart, nerves, and other organs, increasing the risk for kidney failure, myocardial infarction, stroke, and other problems.

The safety of the drug was studied in four clinical trials involving a total of 139 patients with Fabry disease.

The drug is indicated for adults with Fabry disease who have a genetic mutation determined to be responsive to treatment with Migalastat based on laboratory data.

“Thus far, treatment of Fabry disease has involved replacing the missing enzyme that causes the particular type of fat buildup in this disease. Galafold differs from enzyme replacement in that it increases the activity of the body’s deficient enzyme,” said Julie Beitz, M.D., director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research.

Fabry disease is an inherited disorder caused by mutations (alterations) in the alpha-galactosidase A (GLA) gene located on the X-chromosome. Fabry disease is rare and affects both males and females. It is estimated that classic Fabry disease (the most severe type) affects approximately one in 40,000 males. The later-onset type is more frequent, and in some populations, may occur in one in 1,500 to 4,000 males. Patients with Fabry disease develop slowly progressive kidney disease, cardiac hypertrophy (enlargement of the heart), arrhythmias (abnormal heart rhythm), stroke and early death.

The efficacy of Galafold was demonstrated in a six-month, placebo-controlled clinical trial in 45 adults with Fabry disease. In this trial, patients treated with Galafold over six months had a greater reduction in globotriaosylceramide (GL-3) in blood vessels of the kidneys (as measured in kidney biopsy samples) as compared to patients on placebo. The safety of Galafold was studied in four clinical trials which included a total of 139 patients with Fabry disease.

The most common adverse drug reactions in patients taking Galafold in clinical trials were a headache, nasal and throat irritation (nasopharyngitis), urinary tract infection, nausea, and fever (pyrexia).

"Today is a long-awaited day of celebration for all of us living with and advocating for people with Fabry disease, especially those who have participated in the development of Galafold in the United States," Jack Johnson, founder and executive director, Fabry Support & Information Group, said in a company news release.