Overview
11 DESCRIPTION Migalastat, an alpha-galactosidase A (alpha-Gal A) pharmacological chaperone, is a low molecular weight iminosugar and an analogue of the terminal galactose of globotriaosylceramide (GL-3). Migalastat is present in the form of a hydrochloride salt in GALAFOLD. The chemical name for migalastat hydrochloride is (+)-(2 R ,3 S ,4 R ,5 S )-2-(hydroxymethyl) piperidine-3,4,5-triol...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Migalastat is a pharmacological chaperone that reversibly binds to the active site of the alpha-galactosidase A (alpha-Gal A) protein (encoded by the galactosidase alpha gene, GLA ), which is deficient in Fabry disease. This binding stabilizes alpha-Gal A allowing its trafficking from the endoplasmic reticulum into the lysosome where it exerts its action. In the lysosome, at a lower pH and at a higher concentration of relevant substrates, migalastat dissociates from alpha-Gal A allowing it to break down the glycosphingolipids globotriaosylceramide (GL-3) and globotriaosylsphingosine (lyso-Gb 3 ).
Indications
- 1 INDICATIONS AND USAGE GALAFOLD is indicated for the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene ( GLA ) variant based on in vitro assay data [see Dosage and Administration (2.1) and Clinical Pharmacology (12.1) ] . This indication is approved under accelerated approval based on reduction in kidney interstitial capillary cell globotriaosylceramide (KIC GL-3) substrate [see Clinical Studies (14) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Common Doses
- 123 mg
Dosage
2 DOSAGE AND ADMINISTRATION Select adults with confirmed Fabry disease who have an amenable GLA variant for treatment with GALAFOLD. ( 2.1 ) Treatment is indicated for patients with an amenable GLA variant that is interpreted by a clinical genetics professional as causing Fabry disease (pathogenic, likely pathogenic) in the clinical context of the patient. Consultation with a clinical genetics professional is strongly recommended in cases where the amenable GLA variant is of uncertain clinical significance (VUS, variant of uncertain significance) or may be benign (not causing Fabry disease).
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS Most common adverse drug reactions ≥ 10% are: headache, nasopharyngitis, urinary tract infection, nausea, and pyrexia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amicus Therapeutics at 1-877-4AMICUS or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Interactions
- 7 DRUG INTERACTIONS See Full Prescribing Information for clinically significant drug interactions. (7.1) 7.1 Effect of Other Drugs on GALAFOLD Co-administration of GALAFOLD with caffeine decreases migalastat AUC and C max [see Clinical Pharmacology (12.3) ] which may reduce GALAFOLD efficacy. Avoid co-administration of GALAFOLD with caffeine at least 2 hours before and 2 hours after taking GALAFOLD [see Dosage and Administration (2.2) ] .