COMET post hoc analysis: efficacy of long-term avalglucosidase alfa in subgroups of patients with late-onset Pompe disease

COMET (NCT02782741) is a phase 3 trial comparing the efficacy and safety of avalglucosidase alfa (AVA) and alglucosidase alfa (ALG) in treatment-naïve patients with late-onset Pompe disease. After a 49-week primary analysis period (PAP), patients could enter an extended treatment period (ETP). 100 patients enrolled and were randomized to AVA (n=51) or ALG (n=49). All patients from the AVA-arm continued and 44 patients in the ALG-arm switched to AVA in the ETP. Post hoc subgroup analyses explored the effects of baseline characteristics on efficacy outcomes from baseline to Week 145. Subgroups and analyses included: 1) the impact of baseline age (≥18 to <45y, ≥45y) on the change in 6-minute walk test (6MWT) distance and upright forced vital capacity (FVC) % predicted, 2) the impact of baseline 6MWT (<403.5, ≥403.5 m) on the change in FVC % predicted, and 3) the impact of baseline FVC % predicted (<55, ≥55%) on the change in 6MWT distance. Mean estimates (95% CI) were calculated from linear mixed effects models stratified by treatment group. Overall, the change from baseline to Week 145 was stable or improved for all subgroups analyzed for the different outcomes. Statistically significant changes were observed for the change in 6MWT distance in two subgroups: 1) younger patients in the AVA-arm had a significant improvement from baseline to Week 145 (9.8 [4.4,15.1] m; p=0.0004) and 2) AVA-arm patients with baseline FVC ≥55% had a significant improvement from baseline to Week 145 (6.8 [2.4,11.2] m; p=0.0026). Changes over time remain stable in all other subgroups with nonsignificant p values. These data indicate that the positive changes seen during treatment with AVA are not driven by any subgroup and demonstrate that AVA is effective in patients with varying baseline characteristics. Funded: Sanofi COMET (NCT02782741) is a phase 3 trial comparing the efficacy and safety of avalglucosidase alfa (AVA) and alglucosidase alfa (ALG) in treatment-naïve patients with late-onset Pompe disease. After a 49-week primary analysis period (PAP), patients could enter an extended treatment period (ETP). 100 patients enrolled and were randomized to AVA (n=51) or ALG (n=49). All patients from the AVA-arm continued and 44 patients in the ALG-arm switched to AVA in the ETP. Post hoc subgroup analyses explored the effects of baseline characteristics on efficacy outcomes from baseline to Week 145. Subgroups and analyses included: 1) the impact of baseline age (≥18 to <45y, ≥45y) on the change in 6-minute walk test (6MWT) distance and upright forced vital capacity (FVC) % predicted, 2) the impact of baseline 6MWT (<403.5, ≥403.5 m) on the change in FVC % predicted, and 3) the impact of baseline FVC % predicted (<55, ≥55%) on the change in 6MWT distance. Mean estimates (95% CI) were calculated from linear mixed effects models stratified by treatment group. Overall, the change from baseline to Week 145 was stable or improved for all subgroups analyzed for the different outcomes. Statistically significant changes were observed for the change in 6MWT distance in two subgroups: 1) younger patients in the AVA-arm had a significant improvement from baseline to Week 145 (9.8 [4.4,15.1] m; p=0.0004) and 2) AVA-arm patients with baseline FVC ≥55% had a significant improvement from baseline to Week 145 (6.8 [2.4,11.2] m; p=0.0026). Changes over time remain stable in all other subgroups with nonsignificant p values. These data indicate that the positive changes seen during treatment with AVA are not driven by any subgroup and demonstrate that AVA is effective in patients with varying baseline characteristics. Funded: Sanofi