Abstract
Extending the interval between pegunigalsidase alfa infusions in patients with Fabry disease: Five-year interim results from the ongoing BRIGHT51 study
Molecular genetics and metabolism, Vol.144(2), 108656
02/2025
DOI: 10.1016/j.ymgme.2024.108656
Abstract
Enzyme replacement therapy (ERT) infusions for Fabry disease (FD) given every-2-weeks (E2W) can improve disease course. Pegunigalsidase alfa (PA) is a PEGylated ERT with increased half-life compared with other ERTs, potentially allowing dosing flexibility (1 mg/kg E2W or 2 mg/kg every-4-weeks [E4W]). The 1-year BRIGHT trial showed that adults with clinically stable FD (eGFR slope less negative than −2 mL/min/1.73 m^2/year) switching from another ERT E2W to PA 2 mg/kg E4W tolerated extended dosing intervals well. This 5-year interim analysis from the ongoing BRIGHT51 (NCT03614234) extension evaluates long-term safety and efficacy of 2 mg/kg PA E4W. Outcomes are reported from baseline in BRIGHT to ≥3 years of treatment. Three patients changed to 1 mg/kg E2W (n = 1 deteriorating kidney function, n = 2 pain crises); efficacy analyses only included 2 mg/kg E4W data. Of 29 adults (23 M:6F; mean age 40.9 years), 13 (44.8 %) reported 51 PA-related treatment emergent adverse events (TEAEs; 10.7 % of 477 total TEAEs); none were severe/serious. Nine patients (31.0 %; 8 M:1F) experienced 43 infusion-related reactions (IRRs; 2.4 events/100 infusions; 5/9 patients with IRRs had baseline antidrug antibodies [ADAs]); most IRRs occurred within year 1 (62.8 %). Of nine patients with baseline ADAs, all were male, five seroreverted, three titer-boosted, and one not boosted. Median eGFR slopes (mL/min/1.73 m^2/year) varied between −1.8 and − 2.6 among subpopulations (males, −2.4 vs females, −1.8; ADA−, −1.8 vs ADA+, −2.6). Plasma lyso-Gb3 remained stable in females and showed non-clinically significant increase in males. Other stable parameters included pain and quality-of-life. These outcomes highlight continued tolerability of PA 2 mg/kg E4W in stable adult patients switching from other ERTs. Further investigation is needed to determine the effect of PA E4W dosing on kidney function, however these studies suggest that in ADA− females and males, kidney function is stable.
Details
- Title: Subtitle
- Extending the interval between pegunigalsidase alfa infusions in patients with Fabry disease: Five-year interim results from the ongoing BRIGHT51 study
- Creators
- John A. Bernat - University of IowaMyrl Holida - University of IowaStephen Waldek - University of SunderlandWilliam R. Wilcox - Emory University School of MedicineNicola Longo - University of UtahOzlem Goker-Alpan - Lysosomal & Rare Disorders Research & Treatment Center, Fairfax, VA, USAEric Wallace - University of Alabama at BirminghamPatrick Deegan - University of CambridgeCamilla Tøndel - Haukeland University HospitalFrancois Eyskens - Antwerp University HospitalUlla Feldt-Rasmussen - Copenhagen University HospitalDerralynn Hughes - University College LondonAntonio Pisani - University of Naples Federico IIAnkit Mehta - Baylor University Medical CenterKhan Nedd - Infusion AssociatesDavid G. Warnock - University of Alabama at BirminghamGiovanni Piotti - Chiesi Farmaceutici S.p.A., Parma, ItalyMeng Wang - Chiesi USA, Inc., Boston, MA, USAEinat Almon-Brill - Protalix BioTherapeuticsSari Alon - Protalix BioTherapeuticsRaul Chertkoff - Protalix BioTherapeuticsAleš Linhart - General University Hospital in Prague
- Resource Type
- Abstract
- Publication Details
- Molecular genetics and metabolism, Vol.144(2), 108656
- DOI
- 10.1016/j.ymgme.2024.108656
- ISSN
- 1096-7192
- eISSN
- 1096-7206
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 02/2025
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984780239802771
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