Journal article
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
Journal of Medical Genetics, Vol.61(6), pp.520-530
05/21/2024
DOI: 10.1136/jmg-2023-109445
PMCID: PMC11137442
PMID: 37940383
Abstract
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.
Details
- Title: Subtitle
- 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
- Creators
- Eric Wallace - University of Alabama at BirminghamOzlem Goker-AlpanWilliam Wilcox - Emory UniversityMyrl Holida - University of IowaJohn Bernat - University of IowaNicola Longo - University of UtahAleš Linhart - Charles UniversityDerralynn Hughes - Royal Free London NHS Foundation TrustRobert Hopkin - Cincinnati Children's Hospital Medical CenterCamilla Tøndel - University of BergenMirjam Langeveld - University of AmsterdamPilar GiraldoAntonio PisaniDominique GermainAnkit MehtaPatrick DeeganMaria MolnarDamara OrtizAna JovanovicMichael MurielloBojan VujkovacAlbina NowakTarekegn GeberhiwotIlkka KantolaJasmine KnollStephen WaldekKhan NeddAmel KaraaEinat Brill-AlmonSari AlonRaul ChertkoffRossana RoccoAnat SakovDavid WarnockVirginia KimonisBruce Barshop
- Resource Type
- Journal article
- Publication Details
- Journal of Medical Genetics, Vol.61(6), pp.520-530
- DOI
- 10.1136/jmg-2023-109445
- PMID
- 37940383
- PMCID
- PMC11137442
- NLM abbreviation
- J Med Genet
- ISSN
- 0022-2593
- eISSN
- 1468-6244
- Publisher
- BMJ
- Language
- English
- Date published
- 05/21/2024
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984648354302771
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