Clinical course of patients with Fabry disease who were switched from agalsidase-β to agalsidase-α

Abstract

Background: Between 2009 and 2012, there was a worldwide shortage of agalsidase-β for the treatment of Fabry disease. Therefore, alternative treatments were needed, including switching to a different enzyme-replacement therapy.

Purpose: This is an ongoing observational study assessing the effects of switching from agalsidase-β (1.0 mg/kg every other week) to agalsidase-α (0.2 mg/kg every other week) in 11 patients with Fabry disease.

Methods: Clinical data were collected for 5 years-2 years before switching and 3 years after switching.

Results: Measures of renal function such as estimated glomerular filtration rate remained stable during the 3 years after switching to agalsidase-α. Improvements in cardiac mass were recorded in both male and female patients 12 months after switching to agalsidase-α, and the benefit was maintained during 36 months of follow-up. There was no significant difference in the severity of pain experienced by patients before and after switching enzyme-replacement therapy, and no difference in quality-of-life parameters. Agalsidase-α was generally well tolerated, and no patients experienced allergy or developed antibodies to agalsidase-α.

Conclusion: This observational study supports the safety of switching from agalsidase-β to agalsidase-α at the approved doses, with no loss of efficacy. It also suggests that if an infusion-related allergic reaction occurs in a patient receiving agalsidase-β, switching to agalsidase-α may be a viable option.

Figure 1

Individual cardiac parameters (echocardiography) before and after switching from agalsidase-β to agalsidase-α. (a) Left ventricular mass index (LVMI). (b) Interventricular septal wall diameter (IVSd). (c) Left ventricular posterior wall diameter (LVpwd). (d) Ejection fraction (EF).

Figure 2

Brain natriuretic peptide (BNP) levels. (a) Representative values (RVs) for each term (before and after switching from agalsidase-β to agalsidase-α); (b) group with BNP levels at baseline ≥100 pg/ml (n = 5).

Figure 3

Estimated glomerular filtration rate (eGFR) before and after switching from agalsidase-β to agalsidase-α (key for individual case colors as in Figure 1).

Figure 4

Individual Gb3 and lyso-Gb3 levels. Gb3 (a) and lyso-Gb3 (b) levels before and after switching from agalsidase-β to agalsidase-α (key for individual case colors as in Figure 1).