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The following is a summary of “Mini-COMET Clinical Trial: Safety and Efficacy of Avalglucosidase Alfa after 97 Weeks of Treatment in Children with Infantile-Onset Pompe Disease Previously Treated with Alglucosidase Alfa,” published in the May 2025 issue of Journal of Pediatrics by Kronn et al. 

Researchers conducted a retrospective study to evaluate the long-term safety and efficacy of avalglucosidase alfa in children with infantile-onset Pompe disease (IOPD) who had clinical decline or suboptimal response to prior alglucosidase alfa.  

They executed a phase 2, open-label, ascending-dose Mini-COMET trial with 3 cohorts over a 25-week primary analysis period (PAP) followed by an extension of treatment period (ETP). In the PAP, cohort 1 (n=6) received avalglucosidase alfa 20 mg/kg every other week (qow), cohort 2 (n=5) received 40 mg/kg qow, and cohort 3 included children receiving avalglucosidase alfa 40 mg/kg qow (n=5) or pre-study alglucosidase alfa at stable doses ranging from 20 mg/kg qow to 40 mg/kg weekly (qw) for over 6 months (n=6). All participants completed the PAP and entered the ETP, where those initially on avalglucosidase alfa maintained their dose, while those on alglucosidase alfa switched to avalglucosidase alfa 40 mg/kg qow.  

The results showed that at baseline, children were aged 1–12 years. Interim data (≥97 weeks) included all 22 children, with 20 receiving avalglucosidase alfa 40 mg/kg qow and 2 receiving 20 mg/kg qow during the ETP. Of the 6 children in cohort 1 who received 20 mg/kg qow during the PAP, 4 increased their dose to 40 mg/kg qow due to clinical decline. No deaths or discontinuations occurred by data cut-off. Safety profiles in the PAP and ETP were similar, with no treatment-related serious or severe adverse events (AE) reported. Avalglucosidase alfa was well tolerated, showing no increased safety risks or immunogenicity after switching treatments. Echocardiography indicated sustained normalization of left-ventricular mass Z-scores. The biomarkers of Pompe disease burden decreased, while motor function either improved or stabilized compared to baseline.  

Investigators concluded that long-term treatment with avalglucosidase alfa demonstrated a positive clinical impact in children with IOPD. 

Source: jpeds.com/article/S0022-3476(25)00204-5/abstract