Efficacy and safety of avalglucosidase alfa in participants with late-onset Pompe disease after 145 weeks of treatment during the COMET trial


Clinical Trials

Poster Number: 143


Volker Straub, PhD, Newcastle University, Priya S. Kishnani, MD, Duke University Medical Center, Durham, NC, USA, Jordi Díaz-Manera, MD, PhD, John Walton Muscular Dystrophy Research Centre, Newcastle Upon Tyne, UK, Hani Kushlaf, MD, University of Cincinnati, Cincinnati, OH, USA, Shafeeq Ladha, MD, Gregory W. Fulton ALS and Neuromuscular Center, Barrow Neurological Institute, Phoenix, AZ, USA, Tahseen Mozaffar, MD, University of California Irvine, Antonio Toscano, MD, Reference Center for Rare Neuromuscular Disorders, University of Messina, Messina, Italy, Ans T. van der Ploeg, MD, PhD, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, Paula Clemens, MD, University of Pittsburgh, John Day, MD, PhD, Stanford University, Sergey Illarioshkin, MD, Research Center of Neurology, Moscow, Russia, Mark Robert, MD, Salford Royal NHS Foundation Trust, Salford, UK, Shahram Attarian, MD, Referral Centre for Neuromuscular Diseases and ALS, Hôpital La Timone, Marseille, France, Gerson Carvalho, MD, Instituto Chronos de Apoio à Pesquisa, Brasília, DF, Brazil, Sevim Erdem-Özdamar, MD, Department of Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey, Ozlem Goker-Alpan, MD, Lysosomal and Rare Disorders Research and Treatment Center (LDRTC), Fairfax, VA, USA, Anna Kostera-Pruszczyk, MD, PhD, Department of Neurology, Medical University of Warsaw, Warsaw, Poland, Kristina An Haack, MD, Sanofi, Chilly-Mazarin, France, Olivier Huynh-Ba, MD, Sanofi, Chilly-Mazarin, France, Swathi Tammireddy, MBBS, Sanofi, Cambridge, MA, USA, Nathan Thibault, PharmD, Sanofi, Cambridge, MA, USA, Tianyue Zhou, PhD, Sanofi, Cambridge, MA, USA, Mazen M. Dimachkie, MD, University of Kansas Medical Center, Department of Neurology, Kansas City, KS, USA, Benedikt Schoser; on behalf of the COMET Investigator Group, MD, Friedrich-Baur-Institute, Department of Neurology, LMU Klinikum München, München, Germany

Background: The phase 3 COMET trial (NCT02782741) compares safety and efficacy of avalglucosidase alfa (AVAL) with alglucosidase alfa (ALGLU) in treatment-naïve participants with late-onset Pompe disease. Following a 49-week primary analysis phase (PAP), participants could enter an extended treatment phase (ETP).
Objective: To report the ETP results when participants had received AVAL for ≥145 weeks or ALGLU for 49 weeks followed by AVAL for ≥96 weeks.
Results: 100 participants (aged 16-78 years) enrolled in the PAP. All 51 participants who received AVAL 20 mg/kg every 2 weeks (qow) in the PAP (AVAL-arm) continued this in the ETP. Of 49 participants who received ALGLU 20 mg/kg qow in the PAP, 44 entered the ETP switching to AVAL 20 mg/kg qow (Switch-arm). Trends for improvement or stabilization from Baseline to Week 145 were observed for primary and secondary outcomes of respiratory and motor function. Changes (least squares mean [standard error]) in upright forced vital capacity % predicted: AVAL-arm, +1.43 (1.23); Switch-arm, +1.26 (1.35) 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) during AVAL exposure occurred in 50 (98.0%) AVAL-arm (PAP+ETP) and 43 (97.7%) Switch-arm participants (ETP). 18 (35.3%) AVAL-arm and 12 (27.3%) Switch-arm participants had treatment-emergent serious AEs (SAEs) during AVAL exposure; 4 and 2 of them, respectively, had treatment-related SAEs. 5 participants discontinued during the ETP due to 6 treatment-emergent AEs; 4 were treatment-related (ocular hyperemia and erythema [both in the same participant], urticaria, respiratory distress) and 2 were non-treatment-related (acute myocardial infarction, pancreatic adenocarcinoma). Switch-arm participants showed no safety- or 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 the long-term maintenance of clinically meaningful outcomes with AVAL. Funding: Sanofi.