Abstract
Objectives Report efficacy/safety of avalglucosidase alfa (AVAL) in participants with late-onset Pompe disease in the extended treatment period (ETP) of Phase 3 COMET(NCT02782741) after a 49-week primary analysis period (PAP).
Methods At PAP enrollment, participants were treatment-naïve (n=100; age 16–78 years). All 51 participants receiving AVAL 20mg/kg every 2 weeks (qow) in the PAP continued this in the ETP (AVAL-arm). Of 49 participants receiving alglucosidase alfa (ALGLU) 20mg/kg qow in the PAP, 44 entered the ETP switching to AVAL 20mg/kg qow (Switch-arm).
Results Trends for improvement or stabilization from Baseline to Week 97 were observed for the primary and secondary outcomes of respiratory and motor function. Changes (LSmean[SE]) in forced vital capacity%predicted: AVAL-arm, +2.65[1.05]; Switch-arm, +0.36[1.12] and 6-minute walk test distance: AVAL-arm, +18.60[12.01]m; Switch-arm, +4.56[12.44]m. Similar trends occurred for muscle strength and quality of life measures. Treatment-emergent adverse events (AEs) in the ETP occurred in 49(96%) AVAL-arm and 42(95%) Switch-arm participants. Five discontinued during the ETP due to 6 treatment-emergent AEs; 4 were treatment-related (ocular hyperemia, erythema, urticaria, respiratory distress) and 2 were non-treatment-related (acute myocardial infarction, pancreatic adenocarcinoma). In the ETP, 12 AVAL-arm and 10 Switch-arm participants had treatment-emergent serious AEs (SAEs); 3 and 2 of them, respectively, had treatment-related SAEs. Switch-arm participants showed no safety- or immunogenicity-related concerns.
Conclusions Results show sustained treatment effect and continued benefit with AVAL beyond the PAP, and stabilization of treatment effect after switching from ALGLU to AVAL over 97 weeks, supporting long-term maintenance of clinically meaningful outcomes with AVAL.
Funding Sanofi
