Journal article
Long-term efficacy and safety of pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease: results from up to 5 years of the BRIGHT F51 phase III, open-label extension study
Orphanet journal of rare diseases, Vol.21(1), 185
12/2026
DOI: 10.1186/s13023-026-04303-8
PMCID: PMC13154429
PMID: 41862950
Abstract
Background
Enzyme replacement therapies (ERTs) approved for Fabry disease require infusions every 2 weeks (E2W). Pegunigalsidase alfa, a PEGylated ERT with a prolonged half-life vs. other ERTs, may allow extension of the dosing interval to every 4 weeks (E4W).
Twenty-nine patients were enrolled. Median (interquartile range [IQR]) annualized eGFR slope during treatment was ‒2.2 (‒2.9; ‒1.1) mL/min/1.73 m2/year (males: ‒2.4 [‒2.9; ‒1.0, n = 23]; females: ‒1.8 [‒2.4; ‒1.3, n = 6]; anti-drug antibody [ADA]-positive: ‒2.6 [‒4.0; ‒1.7, n = 9 all male]; ADA-negative: ‒1.8 [‒2.7; ‒0.6, n = 20]). Median (IQR) change in plasma lyso-Gb3 from baseline to Week 208 was 3.2 (‒3.9; 8.5, n = 17) nM in males; concentrations remained low and stable in females. Overall, 51/477 treatment-emergent adverse events in 13 patients (45%) were considered treatment-related (all mild/moderate). Nine patients (31%) experienced mild/moderate infusion-related reactions. One patient developed transient de novo ADAs.
Conclusions
Long-term treatment with pegunigalsidase alfa 2 mg/kg E4W was well-tolerated and maintained disease stability, especially in females and ADA-negative males; more data are needed to better understand outcomes in ADA-positive males. Clinical outcomes should be closely monitored during E4W treatment. The final results of this extension study will further assess the feasibility of this dosing regimen.
Details
- Title: Subtitle
- Long-term efficacy and safety of pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease: results from up to 5 years of the BRIGHT F51 phase III, open-label extension study
- Creators
- Myrl Holida - University of IowaAleš Linhart - Charles UniversityNicola Longo - University of California, Los AngelesEric Wallace - University of Alabama at BirminghamCamilla Tøndel - Haukeland University HospitalDerralynn Hughes - Royal Free London NHS Foundation TrustDavid G Warnock - University of Alabama at BirminghamAntonio Pisani - University of Naples Federico IIFrançois Eyskens - Antwerp University HospitalPatrick Deegan - University of CambridgeUlla Feldt-Rasmussen - University of CopenhagenOzlem Goker-Alpan - Lysosomal and Rare Disorders Research and Treatment CenterAnkit Mehta - Baylor University Medical CenterGiovanni Piotti - Chiesi (Italy)Vito Fichera - Chiesi (Italy)Meng Wang - Chiesi (Italy)Raul Chertkoff - Protalix BioTherapeutics (Israel)Stephen Waldek - University of SunderlandWilliam R Wilcox - Emory UniversityJohn A Bernat - University of Iowa Health Care
- Resource Type
- Journal article
- Publication Details
- Orphanet journal of rare diseases, Vol.21(1), 185
- DOI
- 10.1186/s13023-026-04303-8
- PMID
- 41862950
- PMCID
- PMC13154429
- NLM abbreviation
- Orphanet J Rare Dis
- ISSN
- 1750-1172
- eISSN
- 1750-1172
- Publisher
- Springer Nature; LONDON
- Grant note
- Protalix Biotherapeutics
This study was funded by Protalix Biotherapeutics (until February 28, 2023) and Chiesi Farmaceutici (thereafter). The sponsors participated in the conceptualization, design, analysis, decision to publish, and preparation of the manuscript in collaboration with the authors. The authors confirm independence from the sponsors; the content of the manuscript has not been influenced by the sponsors.
- Language
- English
- Electronic publication date
- 03/20/2026
- Date published
- 12/2026
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9985147194302771
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