Journal Article

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

Toyota, Joji, Fujiyama, Shigetoshi, Linaberry, Misti, Watanabe, Hideaki, Takaguchi, Koichi, McPhee, Fiona, Naganuma, Atsushi, Swenson, Eugene Scott, Yin, Philip D., Tanaka, Katsuaki, Ishikawa, Hiroki, Kumada, Hiromitsu, Suzuki, Fumitaka, Yoshiji, Hitoshi, Hu, Wenhua, Tomita, Eiichi, Chayama, Kazuaki, Ikeda, Fusao, Ido, Akio, Karino, Yoshiyasu, Inada, Yukiko

2017

Overview

Background 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. Methods In this phase 3 study, DCV-TRIO for 12 weeks and daclatasvir plus asunaprevir (DUAL) for 24 weeks were studied in Japanese patients infected with HCV genotype 1 (99 % genotype 1b). Results SVR12 rates ≥95 % were achieved in both treatment-naive ( N  = 152) and interferon-experienced ( N  = 65) cohorts treated with DCV-TRIO for 12 weeks and were comparable across patient subgroups, including patients aged ≥65 years 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 ≥4 weeks 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. Conclusion SVR12 was achieved by 96 % of Japanese patients with HCV genotype 1 infection after 12 weeks of treatment with the DCV-TRIO regimen. DCV-TRIO and DUAL exhibited comparable safety profiles.

• Publisher: Springer Japan,Springer,Springer Nature B.V
• Subject: Abdominal Surgery / Adult / Aged / Aged, 80 and over / Antiviral Agents - administration & dosage / Antiviral Agents - adverse effects / Antiviral Agents - therapeutic use / Benzazepines - administration & dosage / Benzazepines - adverse effects / Benzazepines - therapeutic use / Biliary Tract / Biological products industry / Biological response modifiers / Care and treatment / Colorectal Surgery / Dosage and administration / Double-Blind Method / Drug Administration Schedule / Drug Combinations / Drug therapy, Combination / Female / Gastroenterology / Genetic aspects / Genotype / Health aspects / Hepacivirus - genetics / Hepacivirus - isolation & purification / Hepatitis C virus / Hepatitis C, Chronic - complications / Hepatitis C, Chronic - drug therapy / Hepatitis C, Chronic - virology / Hepatology / Humans / Imidazoles - administration & dosage / Imidazoles - adverse effects / Imidazoles - therapeutic use / Indoles - administration & dosage / Indoles - adverse effects / Indoles - therapeutic use / Interferon / Isoquinolines - administration & dosage / Isoquinolines - adverse effects / Isoquinolines - therapeutic use / Liver cirrhosis / Liver Cirrhosis - virology / Male / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Middle Aged / Original Article—Liver / Pancreas / Protease inhibitors / Proteases / RNA, Viral - blood / Sulfonamides - administration & dosage / Sulfonamides - adverse effects / Sulfonamides - therapeutic use / Surgical Oncology / Sustained Virologic Response / Treatment Outcome