학술논문
P.025 Efficacy and safety results of the avalglucosidase alfa phase 3 COMET trial in participants with late-onset Pompe disease (LOPD)
Document Type
Article
Author
Tarnopolsky, M; Attarian, S; Borges, J; Bouhour, F; Choi, Y; Clemens, P; Day, J; Díaz-Manera, J; Erdem-Ozdamar, S; Goker-Alpan, O; Illarioshkin, S; Kishnani, PS; Kostera-Pruszczyk, A; Kushlaf, H; Ladha, S; Mozaffar, T; Roberts, M; Straub, V; Toscano, A; van der Ploeg, AT; An Haack, K; Hug, C; Huynh-Ba, O; Johnson, J; Zhou, T; Dimachkie, MM; Schoser, B
Source
The Canadian Journal of Neurological Sciences; November 2021, Vol. 48 Issue: Supplement 3 pS27-S27, 1p
Subject
Language
ISSN
03171671
Abstract
Background:Phase 3 COMET trial (NCT02782741) compares avalglucosidase alfa (n=51) with alglucosidase alfa (n=49) in treatment-naïve LOPD. Methods:Primary objective: determine avalglucosidase alfa effect on respiratory muscle function. Secondary/other objectives include: avalglucosidase alfa effect on functional endurance, inspiratory/expiratory muscle strength, lower/upper extremity muscle strength, motor function, health-related quality of life, safety. Results:At Week 49, change (LSmean±SE) from baseline in upright forced vital capacity %predicted was greater with avalglucosidase alfa (2.89%±0.88%) versus alglucosidase alfa (0.46%±0.93%)(absolute difference+2.43%). The primary objective, achieving statistical non-inferiority (p=0.0074), was met. Superiority testing was borderline significant (p=0.0626). Week 49 change from baseline in 6-minute walk test was 30.01-meters greater for avalglucosidase alfa (32.21±9.93m) versus alglucosidase alfa (2.19±10.40m). Positive results for avalglucosidase alfa were seen for all secondary/other efficacy endpoints. Treatment-emergent adverse events (AEs) occurred in 86.3% of avalglucosidase alfa-treated and 91.8% of alglucosidase alfa-treated participants. Five participants withdrew, 4 for AEs, all on alglucosidase alfa. Serious AEs occurred in 8 avalglucosidase alfa-treated and 12 alglucosidase alfa-treated participants. IgG antidrug antibody responses were similar in both. High titers and neutralizing antibodies were more common for alglucosidase alfa. Conclusions:Results demonstrate improvements in clinically meaningful outcome measures and a more favorable safety profile with avalglucosidase alfa versus alglucosidase alfa. Funding:Sanofi Genzyme