Kronn David, Davison James, Broomfield Alexander, Brassier Anaïs, Labarthe François, Hahn Si Houn, Kumada Satoko, Ohki Hirotaka, Prakalapakorn Sasapin Grace, Wilson Catherine, Haack Kristina An, Huynh-Ba Olivier, Richards Susan, Sparks Susan, Tammireddy Swathi, Zhou Tianyue, Chien Yin-Hsiu, Kishnani Priya S
Departments of Pathology and Pediatrics, New York Medical College, Valhalla, NY.
Great Ormond Street Hospital NHS Foundation Trust, London, UK; National Institute of Health Research Great Ormond Street Hospital Biomedical Research Centre, London, UK.
J Pediatr. 2025 Oct;285:114664. doi: 10.1016/j.jpeds.2025.114664. Epub 2025 May 29.
To evaluate the long-term safety and efficacy of avalglucosidase alfa in children with infantile-onset Pompe disease experiencing clinical decline (cohorts 1 and 2) or suboptimal response (cohort 3) to prestudy alglucosidase alfa.
The Mini-COMET clinical trial, a phase 2, open-label, ascending-dose, 3-cohort study, has a 25-week primary analysis period (PAP) and an extension treatment period (ETP). In the PAP, cohorts 1 (n = 6) and 2 (n = 5) received avalglucosidase alfa 20 or 40 mg/kg every other week (qow), respectively. Cohort 3 received avalglucosidase alfa 40 mg/kg qow (n = 5) or alglucosidase alfa (prestudy [>6 months] stable dose: 20 mg/kg qow to 40 mg/kg weekly; n = 6). All children completed the PAP and entered the ETP. Children receiving avalglucosidase alfa in the PAP continued the same dose in the ETP. Those receiving alglucosidase alfa in the PAP received avalglucosidase alfa 40 mg/kg qow in the ETP.
At baseline, children were 1-12 years old. Interim data (≥97 weeks) are presented from all 22 children, 20 receiving avalglucosidase alfa 40 mg/kg qow and 2 receiving 20 mg/kg qow in the ETP. Among the 6 who received 20 mg/kg qow avalglucosidase alfa in PAP (cohort 1), 4 had their dose increase to 40 mg/kg qow because of further clinical decline in the ETP. No child died or discontinued at data cutoff. PAP and ETP safety profiles were similar; no treatment-related serious or severe treatment-emergent adverse events occurred. Avalglucosidase alfa was well-tolerated, with no increased safety risk or immunogenicity concerns post-treatment switch. Echocardiography revealed persistent left ventricular mass z score normalization. Compared with baseline, biomarkers of Pompe disease burden decreased, and motor function improved or stabilized.
Results support the positive clinical impact of long-term avalglucosidase alfa in children with infantile-onset Pompe disease.
ClinicalTrials.gov: NCT03019406.
评估阿伐糖苷酶α对婴儿型庞贝病临床症状恶化（队列1和队列2）或对研究前使用的阿糖苷酶α反应欠佳（队列3）的儿童的长期安全性和疗效。
Mini-COMET临床试验是一项2期、开放标签、剂量递增的3队列研究，有一个25周的主要分析期（PAP）和一个延长期治疗期（ETP）。在PAP中，队列1（n = 6）和队列2（n = 5）分别每隔一周接受20或40 mg/kg的阿伐糖苷酶α。队列3接受40 mg/kg每隔一周的阿伐糖苷酶α（n = 5）或阿糖苷酶α（研究前[>6个月]稳定剂量：20 mg/kg每隔一周至40 mg/kg每周；n = 6）。所有儿童均完成PAP并进入ETP。在PAP中接受阿伐糖苷酶α的儿童在ETP中继续使用相同剂量。在PAP中接受阿糖苷酶α的儿童在ETP中接受40 mg/kg每隔一周的阿伐糖苷酶α。
基线时，儿童年龄为1至12岁。呈现了所有22名儿童的中期数据（≥97周），其中20名在ETP中接受40 mg/kg每隔一周的阿伐糖苷酶α，2名接受20 mg/kg每隔一周的阿伐糖苷酶α。在PAP中接受20 mg/kg每隔一周阿伐糖苷酶α的6名儿童（队列1）中，4名因ETP中临床症状进一步恶化而将剂量增加至40 mg/kg每隔一周。在数据截止时，没有儿童死亡或停药。PAP和ETP的安全性概况相似；未发生与治疗相关的严重或严重的治疗中出现的不良事件。阿伐糖苷酶α耐受性良好，治疗转换后没有增加的安全风险或免疫原性问题。超声心动图显示左心室质量z评分持续正常化。与基线相比，庞贝病负担的生物标志物下降，运动功能改善或稳定。
结果支持长期使用阿伐糖苷酶α对婴儿型庞贝病儿童的积极临床影响。
ClinicalTrials.gov：NCT03019406。
