Pegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy.
BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase
beta in adults with Fabry disease with an annualised estimated glomerular filtration
rate (eGFR) slope more negative than -2 mL/min/1.73 m2/year who had received agalsidase
beta for ≥1 year.Patients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase
alfa or agalsidase beta every 2 weeks for 2 years. The primary efficacy analysis assessed
non-inferiority based on median annualised eGFR slope differences between treatment
arms.Seventy-seven patients received either pegunigalsidase alfa (n=52) or agalsidase
beta (n=25). At baseline, mean (range) age was 44 (18-60) years, 47 (61%) patients
were male, median eGFR was 74.5 mL/min/1.73 m2 and median (range) eGFR slope was -7.3
(-30.5, 6.3) mL/min/1.73 m2/year. At 2 years, the difference between median eGFR slopes
was -0.36 mL/min/1.73 m2/year, meeting the prespecified non-inferiority margin. Minimal
changes were observed in lyso-Gb3 concentrations in both treatment arms at 2 years.
Proportions of patients experiencing treatment-related adverse events and mild or
moderate infusion-related reactions were similar in both groups, yet exposure-adjusted
rates were 3.6-fold and 7.8-fold higher, respectively, with agalsidase beta than pegunigalsidase
alfa. At the end of the study, neutralising antibodies were detected in 7 out of 47
(15%) pegunigalsidase alfa-treated patients and 6 out of 23 (26%) agalsidase beta-treated
patients. There were no deaths.Based on rate of eGFR decline over 2 years, pegunigalsidase
alfa was non-inferior to agalsidase beta. Pegunigalsidase alfa had lower rates of
treatment-emergent adverse events and mild or moderate infusion-related reactions.NCT02795676.
