• Fabry Disease
• alpha-Galactosidase
• Antigenic Variation

With great interest, we followed the recent studies by Linhart and colleagues1 as well as Wallace and colleagues.2 Especially the outcomes of the latter study were decisive for approval of pegunigalsidase alfa as a new enzyme replacement therapy in patients with Fabry disease (FD) by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) in May 2023.

In the BRIDGE study, the authors report about the safety and efficacy in patients with FD under pegunigalsidase alfa, previously treated with agalsidase alfa.1 Overall, the annualised slope of the estimated glomerular filtration rate (eGFR) changed from −5.90 mL/min/1.73 m²/year under agalsidase alfa to −1.19 mL/min/1.73 m²/year under pegunigalsidase alfa. As a biochemical response, treatment with pegunigalsidase alfa led to a mean plasma lyso-Gb₃ reduction by 31.5%. In terms of immunogenicity, seven (35%) patients were positive for antidrug antibodies (ADA) at least once during the study. In detail, five patients were ADA-negative at baseline and thus showed a de novo ADA formation. Three of five returned ADA negative at the end of the study.1 In the BALANCE study, the authors reported the non-inferiority of pegunigalsidase alfa compared to agalsidase beta after 24 months of treatment.2 In detail, median (95% CI limits) eGFR slopes after 24 months of treatment were −2.51 (−3.79, −1.24) mL/min/1.73 m²/year with pegunigalsidase alfa and −2.16 (−3.81, –0.51) mL/min/1.73 m²/year with agalsidase beta. The difference in median eGFR slope for the intent-to-treat population between arms was −0.36 mL/min/1.73 m^{2 …}