The 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.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: Results support the positive clinical impact of long-term avalglucosidase alfa in children with infantile-onset Pompe disease. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03019406.

Duke Scholars

Author Priya Sunil Kishnani Pediatrics, Medical Genetics

Author Grace Prakalapakorn Ophthalmology