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

Joji Toyota, Yoshiyasu Karino, Fumitaka Suzuki, Fusao Ikeda, Akio Ido, Katsuaki Tanaka, Koichi Takaguchi, Atsushi Naganuma, Eiichi Tomita, Kazuaki Chayama, Shigetoshi Fujiyama, Yukiko Inada, Hitoshi Yoshiji, Hideaki Watanabe, Hiroki Ishikawa, Wenhua Hu, Fiona McPhee, Misti Linaberry, Philip D. Yin, Eugene Scott Swenson & 1 others Hiromitsu Kumada

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalJournal of Gastroenterology
DOIs
Publication statusAccepted/In press - Aug 9 2016

Fingerprint

Genotype
Infection
Galectin 3
Therapeutics
8-cyclohexyl-N-((dimethylamino)sulfonyl)-1,1a,2,12b-tetrahydro-11-methoxy-1a-((3-methyl-3,8-diazabicyclo(3.2.1)oct-8-yl)carbonyl)cycloprop(d)indolo(2,1-a)(2)benzazepine-5-carboxamide
BMS-790052
asunaprevir
Protease Inhibitors
Interferons
Fibrosis
Safety
Liver

Keywords

  • Direct-acting antiviral
  • HCV therapy
  • NS3/4A inhibitor
  • NS5A inhibitor
  • NS5B inhibitor

ASJC Scopus subject areas

  • Medicine(all)
  • Gastroenterology

Cite this

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

In: Journal of Gastroenterology, 09.08.2016, p. 1-11.

Research output: Contribution to journalArticle

Toyota, J, Karino, Y, Suzuki, F, Ikeda, F, Ido, A, Tanaka, K, Takaguchi, K, Naganuma, A, Tomita, E, Chayama, K, Fujiyama, S, Inada, Y, Yoshiji, H, Watanabe, H, Ishikawa, H, Hu, W, McPhee, F, Linaberry, M, Yin, PD, Swenson, ES & Kumada, H 2016, 'Daclatasvir/asunaprevir/beclabuvir fixed-dose combination in Japanese patients with HCV genotype 1 infection', Journal of Gastroenterology, pp. 1-11. https://doi.org/10.1007/s00535-016-1245-6
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. / Daclatasvir/asunaprevir/beclabuvir fixed-dose combination in Japanese patients with HCV genotype 1 infection. In: Journal of Gastroenterology. 2016 ; pp. 1-11.
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title = "Daclatasvir/asunaprevir/beclabuvir fixed-dose combination in Japanese patients with HCV genotype 1 infection",
abstract = "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.",
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author = "Joji Toyota and Yoshiyasu Karino and Fumitaka Suzuki and Fusao Ikeda and Akio Ido and Katsuaki Tanaka and Koichi Takaguchi and Atsushi Naganuma and Eiichi Tomita and Kazuaki Chayama and Shigetoshi Fujiyama and Yukiko Inada and Hitoshi Yoshiji and Hideaki Watanabe and Hiroki Ishikawa and Wenhua Hu and Fiona McPhee and Misti Linaberry and Yin, {Philip D.} and Swenson, {Eugene Scott} and Hiromitsu Kumada",
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T1 - Daclatasvir/asunaprevir/beclabuvir fixed-dose combination in Japanese patients with HCV genotype 1 infection

AU - Toyota, Joji

AU - Karino, Yoshiyasu

AU - Suzuki, Fumitaka

AU - Ikeda, Fusao

AU - Ido, Akio

AU - Tanaka, Katsuaki

AU - Takaguchi, Koichi

AU - Naganuma, Atsushi

AU - Tomita, Eiichi

AU - Chayama, Kazuaki

AU - Fujiyama, Shigetoshi

AU - Inada, Yukiko

AU - Yoshiji, Hitoshi

AU - Watanabe, Hideaki

AU - Ishikawa, Hiroki

AU - Hu, Wenhua

AU - McPhee, Fiona

AU - Linaberry, Misti

AU - Yin, Philip D.

AU - Swenson, Eugene Scott

AU - Kumada, Hiromitsu

PY - 2016/8/9

Y1 - 2016/8/9

N2 - 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.

AB - 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.

KW - Direct-acting antiviral

KW - HCV therapy

KW - NS3/4A inhibitor

KW - NS5A inhibitor

KW - NS5B inhibitor

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