Abstract
Objectives Report efficacy/safety of avalglucosidase alfa (AVAL) in participants with late-onset Pompe disease in the extended-treatment period (ETP) of COMET (NCT02782741) at 145 weeks from treatment initiation.
Methods Following a 49-week primary-analysis period (PAP), participants could enter the ETP. 100 participants (age 16–78 years) enrolled in the PAP.
Results All 51 who received AVAL 20mg/kg every 2 weeks (qow) in the PAP (AVAL-arm) continued this in the ETP. Of 49 who received alglucosidase alfa (ALGLU) 20mg/kg qow in the PAP, 44 entered the ETP switching to AVAL 20mg/kg qow (Switch-arm). Improvement or stabilization trends from Baseline to Week 145 were observed for primary and secondary outcomes of respiratory and motor function. Changes (LS mean[SE]) in upright forced vital capacity%predicted: AVAL-arm, +1.40(1.21); Switch-arm, +1.18(1.32) and 6-minute walk test distance: AVAL-arm, +20.65(9.60)m; Switch-arm, +0.29(10.42)m. Similar trends occurred in other Week-145 outcomes. Treatment-emergent adverse events (AEs) in the ETP occurred in 49(96.1%) AVAL-arm and 43(97.7%) Switch-arm participants. Five discontinued during the ETP for 6 treatment-emergent AEs; 4 treatment-related (ocular hyperemia, erythema [in same participant], urticaria, respiratory distress) and 2 non-treatment-related (acute myocardial infarction, pancreatic adenocarcinoma). In the ETP, 13(25.5%) AVAL-arm and 12(27.3%) 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/immunogenicity-related concerns.
Conclusions Week 145 results show sustained treatment effect and continued benefit with AVAL beyond the PAP, and stabilization of treatment effect after switching from ALGLU to AVAL, supporting long-term maintenance of clinically meaningful outcomes with AVAL.
Funding: Sanofi.
