A Multi-Centre Prospective Study of the Efficacy and Safety of Alglucosidase Alfa in Chinese Patients With Infantile-Onset Pompe Disease

Frontiers in Pharmacology

Diqi Zhu¹  Xiaodan Yu²  Zhenheng Ou³  Lin Liu³  Cong Liu³  Wenjuan Qiu⁴  Jiacong Zhu⁵  Guangsong Shan⁶  Benzhen Wang⁶  Zipu Li⁶  Bin Li⁷  Xiaokang Chen⁷  Jian Wang⁸  Lijun Fu⁹ 

[1] Department of Cardiology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Developmental and Behavioral Pediatrics, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Pediatric Cardiology, Shenzhen Children’s Hospital, Shenzhen, China;Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Pediatrics, The Second Hospital of Jiaxing, Jiaxing, China;Heart Center, Women and Children’s Hospital, Qingdao University, Qingdao, China;Medical Department, Sanofi Investment Co., Ltd., Shanghai, China;Research Division of Birth Defects, Institute of Pediatric Translational Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Shanghai Clinical Research Center for Rare Pediatric Disease, Shanghai, China;

关键词: Pompe disease;    glycogen storage disease type II;    enzyme replacement therapy;    alglucosidase alfa;    survival rate;    left ventricular mass index;   

DOI  :  10.3389/fphar.2022.903488

来源: DOAJ

【 摘 要 】

Background: A high prevalence of infantile-onset Pompe disease (IOPD) in the Chinese population has been noted, but there are currently no reported clinical trials of enzyme replacement therapy (ERT) for IOPD in this population. The purpose of this study was to evaluate the efficacy and safety of alglucosidase alfa in Chinese patients with IOPD.Materials and Methods: A multicentre, single-arm, prospective, open-label clinical trial was performed at 4 sites in China. Eligible Chinese subjects with IOPD received an infusion of alglucosidase alfa at a dose of 20 mg/kg every 2 weeks for up to 52 weeks. The primary endpoints of clinical efficacy were the survival rate and changes in the left ventricular mass index (LVMI). The safety assessment was based on the incidence of adverse events (AEs).Results: A total of 10 eligible subjects were enrolled in the study. The mean age at the start of ERT was 5.36 ± 1.56 months. Nine subjects had survived after 52 weeks of treatment. One subject discontinued the study and died after mechanical ventilation was withdrawn. The intent-to-treat analysis demonstrated that the survival rate was 90.0% (95% confidence interval: 55.5–99.7%). The mean LVMI at week 52 was 70.59 ± 39.93 g/m2 compared to that of 298.02 ± 178.43 g/m2 at baseline, with a difference of -227.60 ± 155.99 g/m2. All subjects had left ventricular mass (LVM) Z scores >10 at baseline, and eight subjects (80%) achieved Z scores <5 at week 52. No treatment-related AEs were observed, and no AEs led to the discontinuation of treatment.Conclusions: This clinical trial is the first study of ERT for IOPD in China, indicating that alglucosidase alfa has favourable efficacy and safety for the treatment of Chinese patients with IOPD (ClinicalTrials.gov number, NCT03687333).

【 授权许可】

Unknown