%0 Journal Article
%T Head-to-head trial of pegunigalsidase alfa versus agalsidase beta in patients with Fabry disease and deteriorating renal function: results from the 2-year randomised phase III BALANCE study.
%A Wallace EL
%A Goker-Alpan O
%A Wilcox WR
%A Holida M
%A Bernat J
%A Longo N
%A Linhart A
%A Hughes DA
%A Hopkin RJ
%A Tøndel C
%A Langeveld M
%A Giraldo P
%A Pisani A
%A Germain DP
%A Mehta A
%A Deegan PB
%A Molnar MJ
%A Ortiz D
%A Jovanovic A
%A Muriello M
%A Barshop BA
%A Kimonis V
%A Vujkovac B
%A Nowak A
%A Geberhiwot T
%A Kantola I
%A Knoll J
%A Waldek S
%A Nedd K
%A Karaa A
%A Brill-Almon E
%A Alon S
%A Chertkoff R
%A Rocco R
%A Sakov A
%A Warnock DG
%J J Med Genet
%V 61
%N 6
%D 2024 May 21
%M 37940383
%F 5.941
%R 10.1136/jmg-2023-109445
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.<BR><B>BACKGROUND: </B>NCT02795676.