TY - JOUR
T1 - Head-to-head trial of pegunigalsidase alfa versus agalsidase beta in patients with Fabry disease and deteriorating renal function
T2 - Results from the 2-year randomised phase III BALANCE study
AU - Wallace, Eric L.
AU - Goker-Alpan, Ozlem
AU - Wilcox, William R.
AU - Holida, Myrl
AU - Bernat, John
AU - Longo, Nicola
AU - Linhart, Aleš
AU - Hughes, Derralynn A.
AU - Hopkin, Robert J.
AU - Tøndel, Camilla
AU - Langeveld, Mirjam
AU - Giraldo, Pilar
AU - Pisani, Antonio
AU - Germain, Dominique Paul
AU - Mehta, Ankit
AU - Deegan, Patrick B.
AU - Molnar, Maria Judit
AU - Ortiz, Damara
AU - Jovanovic, Ana
AU - Muriello, Michael
AU - Barshop, Bruce A.
AU - Kimonis, Virginia
AU - Vujkovac, Bojan
AU - Nowak, Albina
AU - Geberhiwot, Tarekegn
AU - Kantola, Ilkka
AU - Knoll, Jasmine
AU - Waldek, Stephen
AU - Nedd, Khan
AU - Karaa, Amel
AU - Brill-Almon, Einat
AU - Alon, Sari
AU - Chertkoff, Raul
AU - Rocco, Rossana
AU - Sakov, Anat
AU - Warnock, David G.
N1 - Funding Information: Protalix Biotherapeutics, Inc. provided financial and material support for the research and, with the assistance of the study investigators, monitored the conduct of the study, collected data from the investigative centers, and analysed and interpreted the data. The authors confirm independence from the sponsors, the content of the article has not been influenced by the sponsors, and the decision to submit it for publication was made by the authors independently. Professional medical writing and editing support were funded by Chiesi USA, Inc. Funding Information: We thank all the patients, their families, the investigators and all study staff involved in this study. The authors would like to acknowledge the Bioanalytical Laboratory at Protalix for assistance with the ADA analysis, and the CHUS laboratory for assistance with the Lyso-Gb3 analysis. Medical writing support was provided by Marisa DeGuzman, PhD, of Oxford PharmaGenesis, Inc., Newtown, PA, USA, and was funded by Chiesi USA, Inc. Publisher Copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023
Y1 - 2023
N2 - 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. Trial registration number: NCT02795676.
AB - 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. Trial registration number: NCT02795676.
KW - Drug-Related Side Effects and Adverse Reactions
KW - Fabry Disease
KW - Genetic Diseases, Inborn
KW - Genetic Diseases, X-Linked
KW - alpha-Galactosidase
UR - http://www.scopus.com/inward/record.url?scp=85176409620&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/jmg-2023-109445
DO - https://doi.org/10.1136/jmg-2023-109445
M3 - Article
C2 - 37940383
SN - 0022-2593
JO - Journal of medical genetics
JF - Journal of medical genetics
M1 - jmg-2023-109445
ER -