Galafold (migalastat) for Fabry disease

Last updated March 6, 2024, by Marisa Wexler, MS
Fact-checked by Ana de Barros, PhD

What is Galafold for Fabry disease?

Galafold (migalastat) is an oral chaperone therapy that’s approved for adults with Fabry disease carrying certain mutations in the GLA gene, the gene that’s deficient in Fabry.

Developed by Amicus Therapeutics, the therapy works to reduce the accumulation of toxic fatty molecules in cells to slow or prevent organ function decline. It was the first treatment in its class, and the first oral therapy for Fabry to win widespread approvals.

Therapy snapshot

How does Galafold work?

Fabry disease is caused by mutations in the GLA gene, which provides instructions for making the enzyme alpha-galactosidase A (Gal A). This enzyme is active in lysosomes — organelles that function as the cells’ waste disposal system — and it’s needed to break down certain fatty molecules such as globotriaosylceramide (Gb3 or GL-3) and lyso-Gb3.

Because people with Fabry disease produce either very little or an abnormal version of the Gal A enzyme, these fatty molecules build to toxic levels in numerous tissues and organs, ultimately causing the damage that drives disease symptoms.

Galafold is a chaperone therapy that works by binding to certain abnormal versions of the Gal A enzyme, those that retain some activity but are not properly folded and are less stable than the healthy protein. Chaperones are naturally occurring proteins that assist in the folding, stabilization, and transportation of other proteins within cells, ensuring they acquire a proper three dimensional conformation and function normally.

By binding the abnormal Gal A, Galafold helps to stabilize the protein and facilitates its proper trafficking to lysosomes, which boosts Gal A’s function and improves the clearance of Gb3 and lyso-Gb3.

Galafold, however, is only able to work in patients with mutations that are amenable to the chaperone therapy.

Who can take Galafold?

The U.S. Food and Drug Administration (FDA) gave accelerated approval to Galafold in August 2018 for the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable GLA mutation (a full list of amenable mutations is available in Table 2 of the therapy’s prescribing information).

The FDA gives accelerated approval to medicines that are likely to be effective based on biomarker data from early trials, but where the clinical meaningfulness of treatment remains unproven. Galafold’s approval was based on data showing that the therapy could reduce the amount of Gb3 in the kidneys, but additional data may be needed to confirm its benefits in clinical outcomes.

In the European Union, Galafold has been approved since 2016 for adults and adolescents, ages 12 and older, with a confirmed diagnosis of Fabry disease and an amenable mutation. The therapy also is approved in various other countries, including Australia, Canada, Israel, Japan, South Korea, Switzerland, and Argentina.

Who should not use Galafold?

Galafold’s label lists no contraindications to its use. However, the therapy is not recommended for patients with severe kidney problems or those in an advanced stage of kidney disease who need dialysis.

How is Galafold administered in Fabry disease?

Galafold is available in hard gelatin capsules that contain 123 mg of the active ingredient, migalastat. Each capsule has an opaque blue cap and an opaque white body that’s printed with “A1001” in black.

The recommended dosage of Galafold is 123 mg, or one capsule, taken by mouth every other day. These capsules should be taken at the same time each day, and not on two consecutive days.

Galafold’s capsules should be swallowed whole (not cut, crushed, or chewed) on an empty stomach. Patients should abstain from food or caffeine for at least two hours before and after taking Galafold, for a minimum fasting period of four hours. However, plain, flavored, or sweetened water; fruit juices without pulp; and caffeine-free carbonated beverages can be consumed during this period.

If a dose is missed, the missed dose can be taken only within 12 hours of when it should have been taken. If more than 12 hours since the scheduled dose have passed, patients should skip that dose entirely and resume the next scheduled dose according to the every-other-day schedule.

Galafold in clinical trials

Regulatory approvals of Galafold were based primarily on data from a Phase 3 clinical trial called FACETS (NCT00925301), which was conducted across various locations in Australia, Canada, Egypt, Europe, Latin America, and the United States.

FACETS

The Amicus-sponsored FACETS study evaluated the safety and efficacy of Galafold in 67 people with Fabry disease, ages 16 to 74, who had never received enzyme replacement therapy (ERT) or who had been off ERT for at least six months before entering the trial. A total of 50 patients, 32 females and 18 males, had GLA mutations amenable to the treatment.

For the first six months of the study, participants were randomly assigned to treatment with Galafold or to a placebo every other day. Then, for the next six months, all participants were treated with Galafold.

Those who completed the yearlong study had the option to continue receiving Galafold treatment in an open-label extension study (NCT01458119), which also included patients from other Galafold trials.

FACETS’ main goal was to assess the proportion of patients who had at least 50% clearance of Gb3 clumps from the kidneys after the trial’s first six months. Results showed no difference between Galafold and placebo in the overall study population: 41% of patients on Galafold and 28% on a placebo had a response at six months.

However, analyses that included only those patients with amenable mutations showed that Gb3 aggregates decreased significantly more with Galafold, as measured by a 0.25 reduction in the mean number of Gb3 inclusions per kidney interstitial capillary compared with a 0.07 increase in patients given a placebo.

These reductions remained stable after an additional six months of treatment. Significant reductions in Gb3 levels also were observed in placebo patients with amenable mutations who switched to Galafold after the study’s first part. Similar dynamics were observed in both groups in the levels of lyso-Gb3, another fatty molecule that’s broken down by Gal A.

In turn, study participants with GLA mutations that were not amenable to the chaperone therapy did not show any treatment effect regarding Gb3 accumulation in the kidneys.

Analyses from the FACETS trial also indicated that Galafold treatment reduced damage to the kidney and heart and eased gastrointestinal symptoms such as diarrhea, reflux, and indigestion.

ATTRACT

As FACETS tested Galafold against a placebo, Amicus launched another Phase 3 study to determine how the therapy would compare to standard ERT therapies.

The ATTRACT clinical trial (NCT01218659) involved 68 people with Fabry, ages 16 to 74, all of whom had been receiving an ERT (either Fabrazyme or agalsidase alfa, the latter not approved in the U.S.) for at least one year prior to enrollment.

Participants were randomly assigned to continue taking their ERT therapy or to switch to Galafold for 18 months. Among the 57 patients who ultimately were included in the trial, 53 had amenable GLA mutations. The study was open label, meaning patients were aware of which therapy they were taking.

ATTRACT’s main goal was to determine changes in kidney function after 18 months. Results showed that both treatments had comparable effects on renal function for patients with amenable mutations.

No patient died during the trial, and the proportion of patients who experienced kidney, heart, or cerebrovascular events over its 18 months was similar in both groups — 29% with Galafold and 44% with ERT. Data also indicated that plasma lyso-Gb3 levels remained low and stable for patients who switched from ERT to Galafold.

Among the 52 patients who completed the main ATTRACT study, 48 opted to enter an open-label extension trial. There, all patients were treated with Galafold for one year, totaling up to 30 months of treatment among those who had switched to Galafold in the original trial.

Long-term data showed consistent benefits with Galafold’s use, with ERT patients experiencing similar rates of kidney decline after switching to Galafold, and those on continuous Galafold treatment retaining their benefits in terms of kidney function, as well as heart health and other disease signs.

An analysis of data from patients who participated in ATTRACT, FACET, and the relevant extension studies also indicated kidney function was generally stabilized with Galafold for up to 8.5 years of treatment, regardless of prior ERT use and a patient’s sex.

Common side effects of Galafold

The most common side effects of Galafold reported in clinical trials include:

• headache
• the common cold (nasopharyngitis)
• urinary tract infection
• nausea
• fever.

Kidney impairment

Because Galafold is mainly excreted by the kidneys, exposure to the therapy is significantly higher in patients with severe kidney problems. As such, Galafold is not recommended for patients with severe kidney problems or with end-stage kidney disease needing dialysis.

Effects on fertility

No data currently addresses whether Galafold affects fertility in people, but a reduction in fertility was observed in male rats at doses comparable to what is used in humans. This infertility was temporary and reversed when Galafold treatment was stopped.

Use in pregnancy and breastfeeding

While three pregnant women with Fabry disease received Galafold in clinical trials, there is not sufficient data to determine if the drug has any adverse effects on the mother or developing fetus during pregnancy. In animal studies, Galafold has not shown any noteworthy safety issues during pregnancy.

Studies in rats have shown that migalastat — Galafold’s active substance — is present in breast milk, but data in human patients are lacking about the presence of Galafold in human milk, its effects on breastfeeding infants, or its impact on milk production.

Use of Galafold during pregnancy or breastfeeding should be made on an individual basis considering both the potential benefits and risks of continued treatment.

Fabry Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.