Fabry disease: a review of current enzyme replacement strategies

Abstract

Introduction: Fabry disease (OMIM 301500) is an X linked lysosomal storage disorder caused by deficiency of α galactosidase A (AGAL–A). Diverse mutations in the AGAL–A gene result in classic or attenuated forms, which may present to a range of physicians. The diagnosis is often delayed and not all patients with the condition require treatment. Two preparations of enzyme replacement therapy (ERT), agalsidase α pha (Replagal R, Shire HGT) and agalsidase β (Fabrazyme R, Genzyme/Sanofi) are licensed.

Areas covered: This review summarizes the evidence relating to the efficacy and safety of ERT for Fabry disease. Trial data on oral pharmacological chaperones, newer forms of ERT and substrate reduction therapy are also considered.

Expert opinion: The two ERT formulations are generally equivalent in terms of safety and efficacy when used at their licensed doses. Agalsidase α is generally better tolerated, has a shorter infusion time and is less immunogenic. Agalsidase β is often used off licence at reduced doses, which is cost saving, better tolerated and may be equally efficacious in selected patients. Treatment must be commenced before the onset of irreversible organ damage.

Keywords:

• agalsidase α
• agalsidase β
• enzyme replacement
• fabry disease
• pharmacological chaperone
• substrate reduction therapy

Declaration of interest

Prof A Mehta has received honoraria from Shire HGT, Genzyme, Protalix and a research grant from Amigos Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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