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

• Published in: Journal of gastroenterology 2017-03, Vol.52 (3), p.385-395
• Main Authors: Toyota, Joji, Karino, Yoshiyasu, Suzuki, Fumitaka, Ikeda, Fusao, Ido, Akio, Tanaka, Katsuaki, Takaguchi, Koichi, Naganuma, Atsushi, Tomita, Eiichi, Chayama, Kazuaki, Fujiyama, Shigetoshi, Inada, Yukiko, Yoshiji, Hitoshi, Watanabe, Hideaki, Ishikawa, Hiroki, Hu, Wenhua, McPhee, Fiona, Linaberry, Misti, Yin, Philip D., Swenson, Eugene Scott, Kumada, Hiromitsu
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-016-1245-6

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.