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
Language English Country United States Media print-electronic
Document type Journal Article, Clinical Trial, Phase III, Multicenter Study, Research Support, Non-U.S. Gov't
Grant support
Protalix Biotherapeutics
PubMed
39381863
PubMed Central
PMC11667655
DOI
10.1002/jimd.12795
Knihovny.cz E-resources
- Keywords
- Fabry disease, eGFR, enzyme replacement therapy, lysosomal storage disorders, lyso‐Gb3, pegunigalsidase alfa,
- MeSH
- alpha-Galactosidase * administration & dosage therapeutic use MeSH
- Adult MeSH
- Enzyme Replacement Therapy * methods MeSH
- Fabry Disease * drug therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Polyethylene Glycols administration & dosage MeSH
- Recombinant Proteins * administration & dosage therapeutic use MeSH
- Drug Administration Schedule MeSH
- Aged MeSH
- Sphingolipids blood MeSH
- Trihexosylceramides blood MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- agalsidase alfa MeSH Browser
- agalsidase beta MeSH Browser
- alpha-Galactosidase * MeSH
- globotriaosyl lysosphingolipid MeSH Browser
- Polyethylene Glycols MeSH
- Recombinant Proteins * MeSH
- Sphingolipids MeSH
- Trihexosylceramides MeSH
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 m2 (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 m2/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.
Antwerp University Hospital UZA Edegem Belgium
Charles University General University Hospital Prague Czech Republic
Chiesi Farmaceutici S p A Parma Italy
Department of Human Genetics Emory University School of Medicine Atlanta Georgia USA
Department of Product Development Protalix Biotherapeutics Carmiel Israel
Department of Public Health University Federico 2 of Naples Naples Italy
LSDU Royal Free London NHS Foundation Trust and University College London London UK
Lysosomal and Rare Disorders Research and Treatment Center Fairfax Virginia USA
Pediatrics Medical Genetics University of Utah Salt Lake City Utah USA
University of Alabama at Birmingham Birmingham Alabama USA
University of Bergen and Haukeland University Hospital Bergen Norway
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