Journal article
A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies
Journal of inherited metabolic disease, Vol.48(1), e12795
01/2025
DOI: 10.1002/jimd.12795
PMCID: PMC11667655
PMID: 39381863
Appears in UI Libraries Support Open Access
Abstract
Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m
(n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m
/year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.
Details
- Title: Subtitle
- A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies
- Creators
- Myrl Holida - University of IowaAleš Linhart - Charles UniversityAntonio Pisani - University of Naples Federico IINicola Longo - University of UtahFrançois Eyskens - Antwerp University HospitalOzlem Goker-Alpan - Lysosomal and Rare Disorders Research and Treatment CenterEric Wallace - University of Alabama at BirminghamPatrick Deegan - Cambridge University Hospitals NHS Foundation TrustCamilla Tøndel - Haukeland University HospitalUlla Feldt-Rasmussen - University of CopenhagenDerralynn Hughes - Royal Free London NHS Foundation TrustAnat Sakov - DataSights Ltd, Haifa, IsraelRossana Rocco - ChiesiEinat Brill Almon - Protalix BioTherapeuticsSari Alon - Protalix BioTherapeuticsRaul Chertkoff - Protalix BioTherapeuticsDavid G Warnock - University of Alabama at BirminghamStephen Waldek - University of SunderlandWilliam R Wilcox - Emory UniversityJohn A Bernat - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of inherited metabolic disease, Vol.48(1), e12795
- DOI
- 10.1002/jimd.12795
- PMID
- 39381863
- PMCID
- PMC11667655
- NLM abbreviation
- J Inherit Metab Dis
- ISSN
- 1573-2665
- eISSN
- 1573-2665
- Publisher
- Wiley
- Grant note
- Protalix Biotherapeutics
- Language
- English
- Electronic publication date
- 10/09/2024
- Date published
- 01/2025
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984722576102771
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