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

Myrl Holida; Aleš Linhart; Nicola Longo; Eric Wallace; Camilla Tøndel; Derralynn Hughes; David G Warnock; Antonio Pisani; François Eyskens; Patrick Deegan; Ulla Feldt-Rasmussen; Ozlem Goker-Alpan; Ankit Mehta; Giovanni Piotti; Vito Fichera; Meng Wang; Raul Chertkoff; Stephen Waldek; William R Wilcox; John A Bernat

doi:10.1186/s13023-026-04303-8

Back

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

Journal article

Open access

Peer reviewed

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

Myrl Holida, Aleš Linhart, Nicola Longo, Eric Wallace, Camilla Tøndel, Derralynn Hughes, David G Warnock, Antonio Pisani, François Eyskens, Patrick Deegan, …

Orphanet journal of rare diseases

03/20/2026

DOI: 10.1186/s13023-026-04303-8

PMID: 41862950

Files and links (1)

url

https://doi.org/10.1186/s13023-026-04303-8View

Published (Version of record) Open Access

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.

eGFR

Fabry disease

Pegunigalsidase alfa

Open-label extension

Lysosomal storage disorders

Enzyme replacement therapy

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 Iowa
Aleš Linhart - Charles University
Nicola Longo - University of California, Los Angeles
Eric Wallace - University of Alabama at Birmingham
Camilla Tøndel - Haukeland University Hospital
Derralynn Hughes - Royal Free London NHS Foundation Trust
David G Warnock - University of Alabama at Birmingham
Antonio Pisani - Department of Public Health, University Federico II of Naples, Naples, Italy
François Eyskens - Antwerp University Hospital
Patrick Deegan - University of Cambridge
Ulla Feldt-Rasmussen - University of Copenhagen
Ozlem Goker-Alpan - Lysosomal and Rare Disorders Research and Treatment Center
Ankit Mehta - Baylor University Medical Center
Giovanni Piotti - Chiesi (Italy)
Vito Fichera - Chiesi (Italy)
Meng Wang - Chiesi (Italy)
Raul Chertkoff - Protalix BioTherapeutics (Israel)
Stephen Waldek - University of Sunderland
William R Wilcox - Emory University
John A Bernat - University of Iowa Health Care
Resource Type: Journal article
Publication Details: Orphanet journal of rare diseases
DOI: 10.1186/s13023-026-04303-8
PMID: 41862950
NLM abbreviation: Orphanet J Rare Dis
ISSN: 1750-1172
eISSN: 1750-1172
Publisher: Springer Nature
Language: English
Electronic publication date: 03/20/2026
Academic Unit: Stead Family Department of Pediatrics; Medical Genetics and Genomics
Record Identifier: 9985147194302771

Metrics

1 Record Views