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
Jazyk angličtina Země Velká Británie, Anglie Médium electronic
Typ dokumentu časopisecké články, randomizované kontrolované studie, klinické zkoušky, fáze III, multicentrická studie
Grantová podpora
UL1 TR001414
NCATS NIH HHS - United States
PubMed
37940383
PubMed Central
PMC11137442
DOI
10.1136/jmg-2023-109445
PII: jmg-2023-109445
Knihovny.cz E-zdroje
- Klíčová slova
- Drug-Related Side Effects and Adverse Reactions, Fabry Disease, Genetic Diseases, Inborn, Genetic Diseases, X-Linked, alpha-Galactosidase,
- MeSH
- alfa-galaktosidasa * terapeutické užití aplikace a dávkování škodlivé účinky genetika MeSH
- dospělí MeSH
- enzymová substituční terapie * metody MeSH
- Fabryho nemoc * farmakoterapie MeSH
- hodnoty glomerulární filtrace * účinky léků MeSH
- izoenzymy * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- rekombinantní proteiny * aplikace a dávkování terapeutické užití škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- agalsidase alfa MeSH Prohlížeč
- agalsidase beta MeSH Prohlížeč
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.
Academisch Medisch Centrum Universiteit van Amsterdam Amsterdam The Netherlands
Baylor University Medical Center at Dallas Dallas Texas USA
Centro de Investigación Biomédica en Red de Enfermedades Raras Zaragoza Spain
Chiesi Farmaceutici SpA Parma Italy
Department of Clinical Science University of Bergen Bergen Norway
Department of Human Genetics Cincinnati Children's Hospital Medical Center Cincinnati Ohio USA
Department of Human Genetics Emory University School of Medicine Atlanta Georgia USA
Department of Internal Medicine General Hospital Slovenj Gradec Slovenj Gradec Slovenia
Department of Pediatrics Haukeland University Hospital Bergen Norway
Department of Pediatrics Medical College of Wisconsin Milwaukee Wisconsin USA
Department of Pediatrics University of California Irvine Irvine California USA
Department of Pediatrics University of California San Diego La Jolla California USA
Department of Pediatrics University of Iowa Hospitals and Clinics Iowa City Iowa USA
Department of Pediatrics UPMC Children's Hospital of Pittsburgh Pittsburgh Pennsylvania USA
Department of Public Health Universita degli Studi di Napoli Federico 2 Napoli Italy
Division of Medical Genetics University of Versailles Garches France
Division of Medicine Turku University Hospital Turku Finland
Infusion Associates Grand Rapids Michigan USA
Lysosomal and Rare Disorders Research and Treatment Center Inc Fairfax Virginia USA
Mark Holland Metabolic Unit Northern Care Alliance NHS Foundation Trust Greater Manchester UK
Massachusetts General Hospital for Children Boston Massachusetts USA
Phoenix Children's Hospital Phoenix Arizona USA
Product Development Protalix Biotherapeutics Carmiel Israel
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ClinicalTrials.gov
NCT02795676