P.025 Efficacy and safety results of the avalglucosidase alfa phase 3 COMET trial in participants with late-onset Pompe disease (LOPD). (November 2021)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Canadian journal of neurological sciences. Volume 48(2021)Supplement S3
• Page Start: S27
• Page End: S27
• Publication Date: 2021-11
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Electronic journals; 616.8
• DOI: 10.1017/cjn.2021.307
• Languages: English
• ISSNs: 0317-1671

Abstract

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