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
Year: 2024
Type: article
Study design: Clinical Trial
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 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.
DOI: 10.1002/jimd.12795
Authors: Myrl Holida, Aleš Linhart, Antonio Pisani, Nicola Longo, François Eyskens, Ozlem Goker‐Alpan, Eric Wallace, Patrick Deegan, Camilla Tøndel, Ulla Feldt‐Rasmussen, Derralynn Hughes, Anat Sakov, Rossana Rocco, Einat Brill Almon, Sari Alon, Raul Chertkoff, David G. Warnock, Stephen Waldek, William R. Wilcox, John A. Bernat
Institutions: University of Iowa, Charles University, General University Hospital in Prague, University of Naples Federico II, University of Utah, Antwerp University Hospital, Lysosomal and Rare Disorders Research and Treatment Center, University of Alabama at Birmingham, University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Haukeland University Hospital, University of Bergen, University of Copenhagen, Rigshospitalet, Royal Free London NHS Foundation Trust, University College London, Chiesi (Italy), Protalix BioTherapeutics (Israel), University of Sunderland, Emory University
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,300
OpenAlex ID: W4403255702