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.