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

• Main Authors: Wallace, Eric, Goker-Alpan, Ozlem, Wilcox, William R, Holida, Myrl, Bernat, John, Longo, Nicola, Linhart, Aleš, Hughes, Derralynn A, Hopkin, Robert, Tøndel, Camilla, Langeveld, Mirjam, Giraldo, Pilar, Pisani, Antonio, Germain, Dominique P, Mehta, Ankit, Deegan, Patrick, Molnar, Maria Judith, Ortiz, Damara, Jovanovic, Ana, Muriello, Michael, Barshop, Bruce, Kimonis, Virginia, Vujkovac, Bojan, Nowak, Albina, Geberhiwot, Tarekegn, Kantola, Ilkka, Knoll, Jasmine, Waldek, Stephen, Nedd, Khan, Karaa, Amel, Brill-Almon, Einat, Alon, Sari, Chertkoff, Raul, Rocco, Rossana, Sakov, Anat, Warnock, David G
• Format: Article
• Language: English

Background 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. Methods 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. Results 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. Conclusions 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.