Dados do Trabalho

Título

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

Resumo

Avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy with increased mannose-6-phosphate content for increased cellular uptake, is approved in the United States for late-onset Pompe disease (LOPD) patients ≥1 year of age and in Japan for all Pompe disease patients (Nexviazyme(TM), Sanofi Genzyme, Cambridge, MA). During the 49-week, double-blinded primary-analysis period (PAP) of the Phase 3 COMET trial (NCT02782741) comparing avalglucosidase alfa with alglucosidase alfa, avalglucosidase alfa resulted in greater improvements in forced vital capacity (FVC), 6-Minute Walk Test (6MWT), and other outcomes and a more favorable safety profile than alglucosidase alfa in treatment-naïve LOPD participants. During the open-label extension treatment period (ETP), 51/51 participants receiving avalglucosidase alfa during the PAP continued this treatment and 44/49 receiving alglucosidase alfa during the PAP switched to avalglucosidase alfa. Changes (LS mean [SE]) from Baseline at Week 97 are reported. Changes in FVC %predicted were +2.65 (1.05) for avalglucosidase alfa PAP participants and +0.36 (1.12) for alglucosidase alfa PAP participants. Changes in 6MWT distance (meters) were +18.60 (12.01) for avalglucosidase alfa PAP participants versus +4.56 (12.44) for alglucosidase alfa PAP participants. Similar trends occurred in other Week-97 outcomes. Treatment-emergent adverse events (AEs) during the ETP occurred in 49 (96.1%) and 42 (95.5%) participants from the avalglucosidase alfa and alglucosidase alfa PAP groups, respectively. Five participants discontinued during the ETP by Week 97 due to AEs (ocular hyperemia, erythema, urticaria, respiratory distress, acute myocardial infarction, pancreatic adenocarcinoma). Twenty-two participants had treatment-emergent serious AEs during the ETP. Patients who switched from alglucosidase alfa to avalglucosidase alfa presented no safety- or immunogenicity-related concerns. Overall results demonstrate sustained treatment effect for improvements observed with avalglucosidase alfa during the PAP and stabilization of treatment effect after switching from alglucosidase alfa to avalglucosidase alfa over 97 weeks, supporting long-term maintenance of outcomes and persistence of avalglucosidase alfa’s effect.