Daclatasvir/asunaprevir/beclabuvir fixed-dose combination in Japanese patients with HCV genotype 1 infection

Abstract

DCV-TRIO, a fixed-dose combination of daclatasvir (pangenotypic NS5A inhibitor), asunaprevir (NS3/4A protease inhibitor), and beclabuvir (non-nucleoside NS5B inhibitor), has achieved high rates of sustained virologic response at post-treatment Week 12 (SVR12) in phase 3 studies. In this phase 3 study, DCV-TRIO for 12weeks and daclatasvir plus asunaprevir (DUAL) for 24weeks were studied in Japanese patients infected with HCV genotype 1 (99% genotype 1b). SVR12 rates ≥95% were achieved in both treatment-naive (N=152) and interferon-experienced (N=65) cohorts treated with DCV-TRIO for 12weeks and were comparable across patient subgroups, including patients aged ≥65years and those with cirrhosis. DUAL recipients (N=75) had an SVR12 rate of 87%. In the absence of baseline resistance-associated polymorphisms at positions NS5A-Y93H or -L31, SVR12 rates were 98% with DCV-TRIO or DUAL. Among genotype 1b-infected patients with baseline Y93H or L31 polymorphisms, 35/38 (92%) DCV-TRIO recipients, and 7/16 (44%) DUAL recipients achieved SVR12. Adverse events, mostly liver related, led to treatment discontinuation in 10% of DCV-TRIO recipients. In this group, SVR12 was achieved by 3/9 patients who discontinued before Week 4 and by 12/12 patients who completed ≥4weeks of DCV-TRIO. Treatment-related serious adverse events occurred in 4 and 3% of DCV-TRIO and DUAL recipients, respectively. Seven patients (9%) discontinued DUAL due to adverse events. No deaths occurred. SVR12 was achieved by 96% of Japanese patients with HCV genotype 1 infection after 12weeks of treatment with the DCV-TRIO regimen. DCV-TRIO and DUAL exhibited comparable safety profiles.