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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

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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Abbreviations

DCV-TRIO:

Fixed-dose combination of daclatasvir/asunaprevir/beclabuvir

NS5A, NS3/4A, NS5B:

HCV nonstructural proteins 5A, 3/4A, or 5B

SVR12:

Sustained virologic response at posttreatment Week 12

DUAL:

Daclatasvir plus asunaprevir

DAA:

Direct-acting antiviral

HCV:

Hepatitis C virus

pegIFN:

Peginterferon

RBV:

Ribavirin

AE:

Adverse event

IFN:

Interferon

ALT:

Alanine aminotransferase

ULN:

Upper limit of normal

INR:

International normalized ratio

EOT:

End of treatment

LLOQ:

Lower limit of quantitation

TD:

Target detected

TND:

Target not detected

RAV:

Resistance-associated variant

AST:

Aspartate aminotransferase

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Acknowledgments

This study was funded and supported by Bristol-Myers Squibb. Editorial support was provided by Jeff Bergen, PhD, of Articulate Science and was funded by Bristol-Myers Squibb.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Sapporo-Kosei General Hospital, 8-5 Higashi Kita-3-jo Chuo-ku, Sapporo-shi, Hokkaido, Japan

    Joji Toyota & Yoshiyasu Karino

  2. Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, Japan

    Fumitaka Suzuki & Hiromitsu Kumada

  3. Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, Japan

    Fusao Ikeda

  4. Kagoshima University, 8-35-1 Sakuragoka, Kagoshima-shi, Kagoshima, Japan

    Akio Ido

  5. Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, Japan

    Katsuaki Tanaka

  6. Kagawa Prefectural Central Hospital, 1-2-1 Asahimachi, Takamatsu-shi, Kagawa, Japan

    Koichi Takaguchi

  7. Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki-shi, Gunma, Japan

    Atsushi Naganuma

  8. Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu-shi, Gifu, Japan

    Eiichi Tomita

  9. Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima-shi, Hiroshima, Japan

    Kazuaki Chayama

  10. Kumamoto Shinto General Hospital, 1-17-27 Shinyashiki, Chuo-ku, Kumamoto, Kumamoto, Japan

    Shigetoshi Fujiyama

  11. Miyazaki Medical Center Hospital, 2-16 Takamatsu-cho, Miyazaki-shi, Miyazaki, Japan

    Yukiko Inada

  12. Nara Medical University, 840 Shijocho, Kashihara-shi, Nara, Japan

    Hitoshi Yoshiji

  13. Bristol-Myers Squibb K.K., 5-1 Nishi-Shinjuku 6-chome, Shinjuku-ku, Tokyo, Japan

    Hideaki Watanabe & Hiroki Ishikawa

  14. Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT, USA

    Wenhua Hu, Fiona McPhee, Philip D. Yin & Eugene Scott Swenson

  15. Bristol-Myers Squibb, 100 Nassau Park Blvd, Princeton, NJ, USA

    Misti Linaberry

Authors
  1. Joji Toyota
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  2. Yoshiyasu Karino
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  3. Fumitaka Suzuki
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  19. Philip D. Yin
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  20. Eugene Scott Swenson
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  21. Hiromitsu Kumada
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Corresponding author

Correspondence to Joji Toyota.

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Conflicts of Interest

J Toyota, A. Ido, and K. Takaguchi have received speaker fees from Bristol-Myers Squibb. Y. Karino has received personal fees from Bristol-Myers K.K. and AbbVie G.K. F. Suzuki has received personal fees from Bristol-Myers Squibb. K. Chayama has received research support from AbbVie, Bristol-Myers Squibb, Dainippon Sumitomo, Eisai, MSD, and Toray; and has received speaker fees from Ajinomoto, AbbVie, Abbott, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eidia, Eisai, Gilead, GlaxoSmithKline, Johnson & Johnson, JIMRO, Mitsubishi Tanabe, Miyarisan, MSD, Nihon Kayaku, Otsuka, Sysmex, and Takeda; and has served as an advisor to AbbVie and Abbott. H. Watanabe, H. Ishikawa, W. Hu, F. McPhee, M. Linaberry, and E.S. Swenson are employees of Bristol-Myers Squibb or Bristol-Myers K.K. P.D. Yin was employed by Bristol-Myers Squibb during the time that the manuscript was developed. H. Kumada has received speaker fees from AbbVie, Bristol-Myers Squibb, Dainippon Sumitomo, Gilead, GlaxoSmithKline, and MSD; and has received patent royalties from SRL. F. Ikeda, K. Tanaka, A. Naganuma, E. Tomita, S. Fujiyama, Y. Inada, and H. Yoshiji have no conflicts of interest to disclose.

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Toyota, J., Karino, Y., Suzuki, F. et al. Daclatasvir/asunaprevir/beclabuvir fixed-dose combination in Japanese patients with HCV genotype 1 infection. J Gastroenterol 52, 385–395 (2017). https://doi.org/10.1007/s00535-016-1245-6

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  • DOI: https://doi.org/10.1007/s00535-016-1245-6

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