Safety and Efficacy of Avalglucosidase Alfa in Individuals With Infantile-Onset Pompe Disease Enrolled in the Phase 2, Open-Label Mini-COMET Study: The 6-Month Primary Analysis Report
PURPOSE: Mini-COMET (NCT03019406; Sanofi) is a phase 2, open-label, ascending-dose, 3-cohort study, evaluating avalglucosidase alfa safety, pharmacokinetics, and efficacy in individuals with infantile-onset Pompe disease aged <18 years who previously received alglucosidase alfa and showed clinical decline (cohorts 1 and 2) or suboptimal response (cohort 3). METHODS: During a 25-week primary analysis period, cohorts 1 and 2 received avalglucosidase alfa 20 and 40 mg/kg every other week, respectively, for 6 months, whereas cohort 3 individuals were randomized (1:1) to receive avalglucosidase alfa 40 mg/kg every other week or alglucosidase alfa (current stable dose) for 6 months. RESULTS: In total, 22 individuals were enrolled (cohort 1 [n = 6], cohort 2 [n = 5], cohort 3-avalglucosidase alfa [n = 5], and cohort 3-alglucosidase alfa [n = 6]). Median treatment compliance was 100%. None of the individuals discontinued treatment or died. Percentages of individuals with treatment-emergent adverse events were similar across dose and treatment groups. No serious or severe treatment-related treatment-emergent adverse events occurred. Trends for better motor function from baseline to week 25 were observed for 40 mg/kg every other week avalglucosidase alfa compared with either 20 mg/kg every other week avalglucosidase alfa or alglucosidase alfa up to 40 mg/kg weekly. CONCLUSION: These data support the positive clinical effect of avalglucosidase alfa in patients with infantile-onset Pompe disease previously declining on alglucosidase alfa.
Kishnani, P. S., Kronn, D., Brassier, A., Broomfield, A., Davison, J., Hahn, S. H., Kumada, S., Labarthe, F., Ohki, H., Pichard, S., Prakalapakorn, S. G., Haack, K. A., Kittner, B., Meng, X., Sparks, S., Wilson, C., Zaher, A., & Chien, Y. (2023). Safety and Efficacy of Avalglucosidase Alfa in Individuals With Infantile-Onset Pompe Disease Enrolled in the Phase 2, Open-Label Mini-COMET Study: The 6-Month Primary Analysis Report. https://doi.org/10.1016/j.gim.2022.10.010