Efficacy of transitioning from alglucosidase alfa to avalglucosidase alfa in infantile-onset Pompe disease: A single-center cohort analysis.
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
Journal Volume
27
Journal Issue
5
ISSN
1530-0366
Date Issued
2025-05
Author(s)
Chien, Yin-Hsuan
Yeh, Chien-Hua
Fang, Ching-Ya
Abstract
Purpose: Although alglucosidase alfa (AGL) is the standard treatment for Pompe disease, its efficacy is limited, partially because of its low mannose-6-phosphate content. Avalglucosidase alfa (AVA), a glycoengineered recombinant human acid α-glucosidase, has shown improved receptor-mediated uptake compared with AGL. Herein, we report the long-term efficacy and safety of AVA in patients with infantile-onset Pompe disease (IOPD) previously treated with AGL. Methods: This retrospective cohort study included 9 patients with IOPD who transitioned from AGL to AVA; these patients were diagnosed and treated after being detected with IOPD via newborn screening. We analyzed the clinical status, biomarker levels (serum creatine kinase and urine glucose tetrasaccharide), and functional assessments before and after AVA treatment of these patients. Statistical analyses were performed using the Wilcoxon matched-pair signed-rank test. Results: Due to inadequate responses, all 9 patients received AGL at dosages exceeding the label recommendations, including one who also had tried cipaglucosidase alfa plus miglustat before transitioning to AVA. After transitioning to AVA at a dosage of 40 mg/kg every other week for a median duration of 4.9 years, the patients experienced significant reductions in biomarker levels (serum creatine kinase levels decreased by 63% and urine glucose tetrasaccharide levels decreased by 69%). Functional assessments, including pulmonary function and 6-minute walk tests, showed improvement in young patients but remained stable in older patients. Safety analyses revealed manageable infusion-associated reactions. Immune modulation therapy for antidrug antibodies was administered to 1 IOPD patient. Conclusion: The transition from a high dose of AGL to AVA demonstrated sustained improvements in biomarker levels and motor function in patients with IOPD. Early initiation of AVA is crucial for patients with IOPD. © 2025 The Authors
Subjects
Biomarker
Cipaglucosidase alfa
Efficacy
Enzyme replacement therapy
Pompe disease
Type
journal article