The Avalglucosidase Alfa Phase 3 COMET Trial in Participants With Late-Onset Pompe Disease: Efficacy and Safety Results After 97 Weeks


Clinical Trials

Poster Number: 69


Hani A. Kushlaf, MD, FAAN, FANA, FAANEM, University of Cincinnati, Cincinnati, OH, USA, Priya Kishnani, MD, Duke University Medical Center, Durham, NC, USA, Jordi Díaz-Manera, MD, Hospital de la Santa Cruz, Barcelona Spain, Shafeeq Ladha, MD, Gregory W. Fulton ALS and Neuromuscular Center, Barrow Neurological Institute, Phoenix, AZ, USA, Tahseen Mozaffar, MD, University of California, Irvine, CA, USA, Volker Straub, MD, PhD, John Walton Muscular Dystrophy Research Centre and Newcastle Hospitals NHS Foundation Trust, UK, 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, Netherlands, Kenneth I. Berger, MD, NYU Grossman School of Med and André Cournand Pulmonary Physiology Laboratory, New York, USA, Paula R. Clemens, MD, University of Pittsburgh School of Medicine, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA, Yin-Hsiu Chien, MD, Department of Medical Genetics and Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, John Day, MD, PhD, Stanford University, Sergey Illarioshkin, MD, Research Center of Neurology, Moscow, Russia, Mark Roberts, MD, PhD, 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, Young Chul Choi, MD, Gangnam Severance Hospital, Yonsei University, College of Medicine, Seoul, Korea, 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, Fairfax, VA, USA, Anna Kostera-Pruszczyk, MD, PhD, Department of Neurology, Medical University of Warsaw, Warsaw, Poland, Kristina An Haack, MD, Sanofi Genzyme, Chilly-Mazarin, France, Olivier Huynh-Ba, MD, Sanofi Genzyme, Chilly-Mazarin, France, Swathi Tammireddy, MBBS, Sanofi Genzyme, Cambridge, MA, USA, Nathan Thibault, PharmD, Sanofi Genzyme, Cambridge, MA, USA, Tianyue Zhou, PhD, Sanofi Genzyme, Cambridge, MA, USA, Mazen M Dimachkie, MD, University of Kansas Medical Center, Department of Neurology, Kansas City, KS, USA, Benedikt Schoser, MD, PhD, Friedrich-Baur-Institut, Ludwig-Maximilians-Universität München, Munich, Germany

Background: Avalglucosidase alfa (AVAL), a recombinant human GAA enzyme replacement therapy with increased mannose-6-phosphate content for increased cellular uptake compared with alglucosidase alfa (ALGLU), is approved in the United States for patients with late-onset Pompe disease (LOPD) aged ?1 year (Nexviazyme™, Sanofi Genzyme, Cambridge, MA).
Objectives: To report the safety and efficacy of AVAL in participants with LOPD in the extended treatment period (ETP) of Phase 3 COMET (NCT02782741) after a 49-week primary analysis period (PAP).
Methods: At PAP enrollment, participants were treatment-naïve (n=100; age 16–78 years). All 51 participants receiving AVAL 20 mg/kg every 2 weeks (qow) in the PAP continued this in the ETP (AVAL-arm). Of the 49 participants receiving ALGLU 20 mg/kg qow in the PAP, 44 entered the ETP and received AVAL 20 mg/kg qow (switch-arm).
Results: Changes (LS mean [SE]) from Week 0–97 in forced vital capacity % predicted were +2.65 (1.05) for AVAL-arm and +0.36 (1.12) for switch-arm participants and changes in 6-minute walk test distance (meters) were +18.60 (12.01) for AVAL-arm and +4.56 (12.44) for switch-arm participants. Similar trends occurred in other Week-97 outcomes. Treatment-emergent adverse events (AEs) in the ETP were seen in 49 (96%) AVAL-arm and 42 (95%) switch-arm participants. 5 participants discontinued treatment during the ETP by Week 97 for AEs (1 event each – treatment-related: ocular hyperemia, erythema, urticaria, respiratory distress; non-treatment related: acute myocardial infarction, pancreatic adenocarcinoma). In the ETP, 12 AVAL-arm and 10 switch-arm participants had treatment-emergent serious AEs (SAEs); 3 and 2 of them, respectively, had SAEs related to treatment. Switch-arm participants showed no safety- or immunogenicity-related concerns.
Conclusions: Results show sustained treatment effect and continued benefit with AVAL beyond the PAP, and stabilization of treatment effect after switching from ALGLU to AVAL over 97 weeks, supporting long-term maintenance of clinically meaningful outcomes with AVAL. Funding: Sanofi Genzyme.