By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The FDA has approved the first oral drug for the treatment of adults with Fabry disease. Migalastat is a pharmacological chaperone, or pharmacoperone, that binds to some forms of faulty alpha-galactosidase A (alpha-Gal A), restoring enzymatic function.1 Migalastat received an accelerated approval and orphan status. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1 It will be marketed as Galafold.


Migalastat is indicated for the treatment of adults with confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene (GLA) variant based on in vitro assay data.1


The recommended dose is one capsule (123 mg) orally once every other day at the same time of day.1 The capsules should be swallowed whole and on an empty stomach (i.e., no food at least two hours before and two hours after). Migalastat is available as 123 mg capsules.


Migalastat provides the first oral option for the treatment of Fabry disease, which generally requires intravenous enzyme replacement therapy (ERT) infusion, usually for life.2


Migalastat was not effective in subjects with nonamenable GLA variants. Common (> 10%) adverse events (vs. placebo) include headache (35% vs. 21%), nasopharyngitis (18% vs. 6%), urinary tract infections (15% vs. 0%), nausea (12% vs. 6%), and pyrexia (12% vs. 3%).1


Pharmacological chaperones are small molecules that cross into cells and target proteins within the cells.3 Fabry disease is an X-linked lysosomal storage disorder caused by a mutation in the GLA gene, resulting in functional deficiency of lysosomal alpha-galactosidase activity. Some variants are folded abnormally and/or are less stable but retain enzymatic activity.1 Migalastat binds reversibly to the active side of alpha-galactosidase of these mutations (amenable variants), acting as molecular scaffolding, stabilizing and “restoring” some of its enzyme function. The efficacy of migalastat was evaluated in 67 adult subjects with Fabry disease and 45 with amenable mutations. These patients had histological data at baseline and at six months.1,4 The primary efficacy endpoints were the proportion of subjects with ≥ 50% reduction from baseline in the average number of globotriaosylceramide (GL-3) inclusions per kidney interstitial capillary assessed by renal biopsy after six months and the median change from baseline in the average number of GL-3 inclusions. Fifty-two percent of patients on migalastat showed ≥ 50% reduction compared to 45% for placebo (not statistically significant). Subjects with baseline GL-3 ≥ 0.3 demonstrated a higher median change from baseline (-0.91 vs. -0.02), with 78% showing ≥ 50% reduction vs. 25% with ≥ 50% reduction for placebo.1 In 56% of subjects who reported diarrhea symptoms at baseline, clinically meaningful improvement was reported with migalastat. Meanwhile, diarrhea worsened in the placebo group.5 Subjects with nonamenable GLA variants showed no change from baseline in GL-3 inclusions.1 In an 18-month study, subjects treated previously with ERT (n = 57) were randomized to migalastat or remained on ERT (agalsidase alfa or beta).6 Annualized glomerular filtration rates from baseline to 18 months were comparable. Left ventricular mass index decreased significantly in favor of migalastat. Plasma globotriaosylsphingosine remained low and stable after switching to migalastat.


Fabry disease is a rare, progressive, life-threatening, X-linked lysosomal storage disorder. The estimated prevalence of classic (severe) disease is 1:40,000 in males,7 although both males and females can be affected. Mutations of the GLA gene result in deficiency of alpha-galactosidase A, leading to accumulation of glycosphingolipids, which is followed by development of progressive renal failure, cardiac hypertrophy, arrhythmias, stroke, and early death.3 Standard therapy is ERT. There are more than 1,000 known GLA mutations. Approximately 35-50% may have amenable mutations.8 These may be stabilized by migalastat, providing an alternative to the traditional ERT. The annual cost for migalastat is $315,250, compared to $306,488 for agalsidase beta (Fabrazyme) for a 70 kg adult.


  1. Galafold Prescribing Information. Amicus Therapeutics, Inc., August 2018. Available to view online at: Accessed Oct. 10, 2018.
  2. National Fabry Disease Foundation. Fabry Disease Treatment. Available at: Accessed Oct. 10, 2018.
  3. Hou ZS, Ulloa-Aguirre A, Tao YX. Pharmacoperone drugs: Targeting misfolded proteins causing lysosomal storage-, ion channels-, and G protein-coupled receptors-associated conformational disorders. Expert Rev Clin Pharmacol 2018;11:611-624.
  4. Germain DP, Hughes DA, Nicholls K, et al. Treatment of Fabry’s disease with the pharmacologic chaperone migalastat. N Engl J Med 2016;375:545-555.
  5. Schiffmann R, Bichet DG, Jovanovic A, et al. Migalastat improves diarrhea in patients with Fabry disease: Clinical-biomarker correlations from the phase 3 FACETS trial. Orphanet J Rare Dis 2018;13:68.
  6. Hughes DA, Nicholls K, Shankar SP, et al. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study. J Med Genet 2017;54:288-296.
  7. U.S. Food & Drug Administration. FDA approves new treatment for a rare genetic disorder, Fabry disease, Aug. 10, 2018. Available to view online at: Accessed Oct. 10, 2018.
  8. Amicus Therapeutics, Inc. Amicus Therapeutics launches Galafold (migalastat) for Fabry disease in Japan. Available at: Accessed Oct. 10, 2018.