From the FDA Drug Label
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. The GLA variants that are amenable to treatment with GALAFOLD, either based on the in vitro assay data or on the concept that synonymous nucleotide changes leading to the same variant alpha-Gal A protein as a confirmed amenable GLA variant are amenable without additional testing, are shown in Table 2 In patients with multiple identified variants, the amenability assessment of each independent variant may not reflect the overall amenability classification of the combination of variants.
Fabry Disease Treatment with Migalastat: Migalastat is used to treat Fabry disease in patients who have an amenable GLA variant. The amenability of a GLA variant is determined by an in vitro assay.
- The drug works by stabilizing the alpha-Gal A protein, allowing it to break down glycosphingolipids.
- Patients with multiple variants should consult a clinical genetics professional to determine the overall amenability classification.
- Table 2 lists the amenable GLA variants that can be treated with migalastat 1.
From the Research
Fabry disease treatment should prioritize enzyme replacement therapy (ERT) with medications like agalsidase beta (Fabrazyme) or agalsidase alfa (Replagal), and for patients with amenable mutations, migalastat (Galafold) is a viable oral option. The disease is a rare genetic disorder caused by mutations in the GLA gene, leading to deficiency of the enzyme alpha-galactosidase A, resulting in accumulation of glycosphingolipids, particularly globotriaosylceramide (Gb3), in various tissues and organs 2.
Key Considerations
- Treatment primarily involves ERT with medications like agalsidase beta (Fabrazyme) administered intravenously every two weeks at 1 mg/kg, or agalsidase alfa (Replagal) at 0.2 mg/kg biweekly 2.
- A newer oral option is migalastat (Galafold), taken every other day for patients with amenable mutations, which has shown to reduce left ventricular mass, stabilize kidney function, and decrease plasma Lyso-Gb3 levels 3.
- Supportive treatments include pain management with anticonvulsants like carbamazepine or gabapentin, ACE inhibitors or ARBs for kidney protection, and statins for cardiovascular complications.
- Early diagnosis and treatment are crucial as they can slow disease progression and prevent irreversible organ damage, with evidence suggesting that ERT can improve left ventricular hypertrophy (LVH) in Fabry disease patients 4.
Management Approach
- Management requires a multidisciplinary approach with regular monitoring of kidney function, cardiac status, and neurological symptoms.
- Genetic counseling is also important for affected families due to the X-linked inheritance pattern of the disease.
- The decision to initiate or cease ERT should be based on individual patient assessment, considering factors such as disease severity, organ involvement, and patient compliance 5.
Recent Evidence
- Recent studies have supported the effectiveness of ERT in improving LVH and stabilizing kidney function in Fabry disease patients 4, and the safety and efficacy of switching from ERT to migalastat in patients with amenable mutations 3.
- The European Fabry Working Group consensus document provides recommendations for the initiation and cessation of ERT in patients with Fabry disease, emphasizing the importance of individualized treatment decisions 5.