Genet Med. 2025 Feb 7:101373. doi: 10.1016/j.gim.2025.101373. Online ahead of print.
ABSTRACT
BACKGROUND: Although alglucosidase alfa (AGL) has been 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.
MATERIALS AND METHODS: This retrospective cohort study included nine 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 [CK] and urine glucose tetrasaccharide ([Glc4]), and functional assessments before and after AVA treatment of these patients. Statistical analyses were performed using the Wilcoxon matched-pair signed-rank test.
RESULTS: All nine patients received AGL at dosages exceeding the label recommendations owing to inadequate responses. 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 (CK levels decreased by 63% and Glc4 levels decreased by 69%). Functional assessments, including pulmonary function and 6-min walk tests, showed improvement in young patients but remained stable in older patients. Safety analyses revealed manageable infusion-associated reactions (IARs). Immune modulation therapy for antidrug antibodies (ADA) was administered to one 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.
PMID:39927452 | DOI:10.1016/j.gim.2025.101373
