Abstract
Clinical assessment of disease severity in patients with Fabry disease treated with pegunigalsidase alfa: An integrated analysis
Molecular genetics and metabolism, Vol.144(2), 108774
02/2025
DOI: 10.1016/j.ymgme.2024.108774
Abstract
Pegunigalsidase alfa (PA) is an approved enzyme replacement therapy (ERT) for Fabry disease (FD) with demonstrated biomarker and clinical benefits. While evaluating kidney function is typically a primary efficacy endpoint in FD trials, the Mainz Severity Score Index (MSSI) provides valuable physician-assessed information on overall disease severity. We analyzed the 24-month change in MSSI in PA-treated patients (ERT-naïve and prior ERT [switch]) from 3 clinical trials (F01/F02, F20, F30) and 1 extension (F03) study. Severity categories are based on overall MSSI score (mild, <20; moderate, ≥20- ≤ 40; severe, >40). Of 87 patients, 39 (45 %) had mild (ERT-naïve: 8/16; ERT-switch: 31/71), 44 (51 %) had moderate (ERT-naïve: 8/16; ERT-switch: 36/71), and 4 (5 %) had severe (ERT-switch: 4/71) overall MSSI at baseline. Overall mean score change from baseline (CFB) to month 12 (standard deviation [SD]) was −1.7 (4.9; n = 80) showing a trend for reduced severity, with improvement in ERT-naïve (−6.3 [4.5]) and stability in ERT-switch patients (−0.5 [4.3]; agalsidase beta to PA: −0.3 [4.4]; agalsidase alfa to PA: −1.0 [4.2]). Severity category changed in 11/80 (14 %) patients: 9 improved (moderate to mild = 8; severe to moderate = 1) and 2 worsened (mild to moderate = 1; moderate to severe = 1; both male with classic FD and antidrug antibody positive). A larger number of ERT-naïve patients with mild disease were observed at month 12 (81 % [13/16]) vs baseline (50 % [8/16]). Among ERT-switch patients, the number with mild disease was stable between baseline (44 % [31/71]) vs month 12 (48 % [31/64]). All MSSI domains showed improvement from baseline as early as month 6. For patients with 24-month data (n = 56), MSSI score CFB improved in ERT-naïve (−7.5 [6.1]) and ERT-switch (−1.9 [5.2]) patients. ERT-naïve patients experience a reduction in disease severity upon PA initiation. In ERT-switch patients, a stable mild/moderate MSSI score is maintained over 12 months, trending toward improvement at 24 months.
Details
- Title: Subtitle
- Clinical assessment of disease severity in patients with Fabry disease treated with pegunigalsidase alfa: An integrated analysis
- Creators
- Derralynn Hughes - University College LondonAleš Linhart - General University Hospital in PragueEric L. Wallace - University of Alabama at BirminghamWilliam R. Wilcox - Emory University School of MedicineChester B. Whitley - University of MinnesotaBojan Vujkovac - Splošna Bolnišnica Slovenj GradecIrene Koulinska - ChiesiGiovanni Piotti - Chiesi USA, Inc., Boston, MA, USARaul Chertkoff - Protalix BioTherapeuticsSari Alon - Protalix BioTherapeuticsAnat Sakov - DataSights, Haifa, IsraelAntonio Pisani - University of Naples Federico IIJohn A. Bernat - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Molecular genetics and metabolism, Vol.144(2), 108774
- DOI
- 10.1016/j.ymgme.2024.108774
- ISSN
- 1096-7192
- eISSN
- 1096-7206
- Publisher
- Elsevier Inc; SAN DIEGO
- Language
- English
- Date published
- 02/2025
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984780353102771
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