Abstract
Improved tolerability following enzyme replacement therapy switch to pegunigalsidase alfa: A case series from two centers of the expanded access program
Molecular genetics and metabolism, Vol.144(2), 108765
02/2025
DOI: 10.1016/j.ymgme.2024.108765
Abstract
Pegunigalsidase alfa (PA) has been studied in >140 patients with Fabry disease (FD), including those switching from another enzyme replacement therapy (ERT). The BALANCE trial, which compared PA to agalsidase beta (AB), showed lower rates of infusion-related reactions (IRRs) among patients switching to PA than those remaining on AB. To further understand this trend, we assessed patients with low AB tolerability switching from AB to PA in the US Expanded Access Program (EAP; NCT04552691) of PA. The EAP allows assessment of PA in patients who cannot be adequately treated with other approved FD therapies and cannot participate in US clinical trials. Results are based on review of medical records. Four patients (3 male, 1 female; 18–51 years [y]; mean EAP duration [range]: 23.6 [10.5–33.0] months), each with >5y of prior ERT were included. On AB, the female patient experienced worsening FD symptoms, especially fatigue, in the days before her next infusion. The 3 males experienced repeated IRRs to AB requiring extensive premedication, including corticosteroids, and prolonged infusions (minimum duration: 150-270 min). Two males tested positive for neutralizing antidrug antibodies to AB before EAP enrollment. As of March 2024, patients had 19–72 PA infusions. Following switch to PA, the female patient reported stable energy between infusions, receiving 60-min infusions without premedication. All males reduced/discontinued premedications with few to no IRRs, discontinued corticosteroids, and 2/3 reduced infusion duration (range: 60-90 min). One mild IRR occurred in a male when premedication was taken too far in advance of the infusion. No patients experienced PA-related serious adverse events. However, 1 male with a history of myocardial infarctions (MI) and atrial fibrillation experienced another MI during the EAP. PA may offer the benefit of lower IRR incidence, reduced infusion durations, and lower premedication burden for some patients with poor tolerability to AB.
Details
- Title: Subtitle
- Improved tolerability following enzyme replacement therapy switch to pegunigalsidase alfa: A case series from two centers of the expanded access program
- Creators
- Myrl D. Holida - University of IowaJohn A. Bernat - University of IowaDawn Laney - Emory University School of Medicine
- Resource Type
- Abstract
- Publication Details
- Molecular genetics and metabolism, Vol.144(2), 108765
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.ymgme.2024.108765
- ISSN
- 1096-7192
- eISSN
- 1096-7206
- Language
- English
- Date published
- 02/2025
- Academic Unit
- Medical Genetics and Genomics; Stead Family Department of Pediatrics
- Record Identifier
- 9984780352002771
Metrics
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