Efficacy of transitioning from alglucosidase alfa to avalglucosidase alfa in infantile-onset Pompe disease: A single-center cohort analysis

IF 6.6 1区医学 Q1 GENETICS & HEREDITY

Genetics in Medicine Pub Date : 2025-02-07 DOI:10.1016/j.gim.2025.101373

Yin-Hsuan Chien , Hui-An Chen , Rai-Hseng Hsu , Chien-Hua Yeh , Ching-Ya Fang , Ni-Chung Lee , Wuh-Liang Hwu , Yin-Hsiu Chien

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引用次数: 0

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.

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来源期刊

Genetics in Medicine 医学-遗传学

CiteScore

15.20

自引率

6.80%

发文量

857

审稿时长

1.3 weeks

期刊介绍： Genetics in Medicine (GIM) is the official journal of the American College of Medical Genetics and Genomics. The journal''s mission is to enhance the knowledge, understanding, and practice of medical genetics and genomics through publications in clinical and laboratory genetics and genomics, including ethical, legal, and social issues as well as public health. GIM encourages research that combats racism, includes diverse populations and is written by authors from diverse and underrepresented backgrounds.