{Reference Type}: Journal Article
{Title}: 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.
{Author}: Wallace EL;Goker-Alpan O;Wilcox WR;Holida M;Bernat J;Longo N;Linhart A;Hughes DA;Hopkin RJ;Tøndel C;Langeveld M;Giraldo P;Pisani A;Germain DP;Mehta A;Deegan PB;Molnar MJ;Ortiz D;Jovanovic A;Muriello M;Barshop BA;Kimonis V;Vujkovac B;Nowak A;Geberhiwot T;Kantola I;Knoll J;Waldek S;Nedd K;Karaa A;Brill-Almon E;Alon S;Chertkoff R;Rocco R;Sakov A;Warnock DG;
{Journal}: J Med Genet
{Volume}: 61
{Issue}: 6
{Year}: 2024 May 21
{Factor}: 5.941
{DOI}: 10.1136/jmg-2023-109445
{Abstract}: <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.