Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1

Jia Horng Kao; Ming Lung Yu; Cheng Yuan Peng; Jeong Heo; Chi Jen Chu; Ting Tsung Chang; Youn Jae Lee; Tsung Hui Hu; Ki Tae Yoon; Seung Woon Paik; Young Suk Lim; Sang Hoon Ahn; Vasily Isakov; Fiona McPhee; Wenhua Hu; Eugene Scott Swenson; Philip D. Yin; Michelle Treitel

doi:10.1111/jgh.13796

Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1

Jia Horng Kao, Ming Lung Yu, Cheng Yuan Peng, Jeong Heo, Chi Jen Chu, Ting Tsung Chang, Youn Jae Lee, Tsung Hui Hu, Ki Tae Yoon, Seung Woon Paik, Young Suk Lim, Sang Hoon Ahn, Vasily Isakov, Fiona McPhee, Wenhua Hu, Eugene Scott Swenson, Philip D. Yin, Michelle Treitel

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

Abstract

Background and Aim: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis. Methods: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n = 138) or treatment-experienced (n = 31), received twice-daily DCV-TRIO for 12 weeks with 24 weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients. Results: Eighty-eight (52%) patients were men, 81 (48%) Taiwanese, 78 (46%) Korean, and 10 (6%) Russian; 23 (14%) had compensated cirrhosis, and 52 (31%) were IL28B (rs1297860) non-CC genotype. Baseline resistance-associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15%) patients with available genotype-1 sequencing data. SVR12 was achieved by 98.6% (136/138; 95% confidence interval: 94.9–99.8%) of treatment-naive and 100% (31/31; 95% confidence interval: 88.8–100%) of treatment-experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype-6g; 100% SVR12 was observed for genotype-1a (n = 8) and genotype-1b (n = 157). Two patients experienced serious adverse events. Eight (5%) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2%); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths. Conclusions: Twelve weeks of DCV-TRIO was well tolerated and provided 100% SVR12 in treatment-naive and treatment-experienced patients with genotype-1 infection, with or without cirrhosis, including those with baseline NS5A-L31 or NS5A-Y93 resistance-associated substitutions.

Original language	English
Pages (from-to)	1998-2005
Number of pages	8
Journal	Journal of Gastroenterology and Hepatology (Australia)
Volume	32
Issue number	12
DOIs	https://doi.org/10.1111/jgh.13796
Publication status	Published - 2017 Dec

Bibliographical note

Funding Information:
The authors thank the patients and their families, study investigators, and site personnel for their participation. The study was funded, designed, and conducted by the sponsor (BMS) in collaboration with the principal investigators. The sponsor collected the data, monitored the study conduct, and performed the statistical analysis. Joseph Ueland, Vincent Vellucci, and Dennis Hernandez are also acknowledged for their efforts obtaining genotypic resistance data on samples from the patients infected with GT-6g. Medical writing assistance was provided by Andrew Street of Articulate Science Ltd, funded by BMS.

Publisher Copyright:
© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

All Science Journal Classification (ASJC) codes

Hepatology
Gastroenterology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/jgh.13796

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Kao, J. H., Yu, M. L., Peng, C. Y., Heo, J., Chu, C. J., Chang, T. T., Lee, Y. J., Hu, T. H., Yoon, K. T., Paik, S. W., Lim, Y. S., Ahn, S. H., Isakov, V., McPhee, F., Hu, W., Scott Swenson, E., Yin, P. D., & Treitel, M. (2017). Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1. Journal of Gastroenterology and Hepatology (Australia), 32(12), 1998-2005. https://doi.org/10.1111/jgh.13796

@article{13ef204d76ff441f885e4a8aa69dbd1a,

title = "Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1",

abstract = "Background and Aim: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis. Methods: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n = 138) or treatment-experienced (n = 31), received twice-daily DCV-TRIO for 12 weeks with 24 weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients. Results: Eighty-eight (52%) patients were men, 81 (48%) Taiwanese, 78 (46%) Korean, and 10 (6%) Russian; 23 (14%) had compensated cirrhosis, and 52 (31%) were IL28B (rs1297860) non-CC genotype. Baseline resistance-associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15%) patients with available genotype-1 sequencing data. SVR12 was achieved by 98.6% (136/138; 95% confidence interval: 94.9–99.8%) of treatment-naive and 100% (31/31; 95% confidence interval: 88.8–100%) of treatment-experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype-6g; 100% SVR12 was observed for genotype-1a (n = 8) and genotype-1b (n = 157). Two patients experienced serious adverse events. Eight (5%) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2%); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths. Conclusions: Twelve weeks of DCV-TRIO was well tolerated and provided 100% SVR12 in treatment-naive and treatment-experienced patients with genotype-1 infection, with or without cirrhosis, including those with baseline NS5A-L31 or NS5A-Y93 resistance-associated substitutions.",

author = "Kao, {Jia Horng} and Yu, {Ming Lung} and Peng, {Cheng Yuan} and Jeong Heo and Chu, {Chi Jen} and Chang, {Ting Tsung} and Lee, {Youn Jae} and Hu, {Tsung Hui} and Yoon, {Ki Tae} and Paik, {Seung Woon} and Lim, {Young Suk} and Ahn, {Sang Hoon} and Vasily Isakov and Fiona McPhee and Wenhua Hu and {Scott Swenson}, Eugene and Yin, {Philip D.} and Michelle Treitel",

note = "Funding Information: The authors thank the patients and their families, study investigators, and site personnel for their participation. The study was funded, designed, and conducted by the sponsor (BMS) in collaboration with the principal investigators. The sponsor collected the data, monitored the study conduct, and performed the statistical analysis. Joseph Ueland, Vincent Vellucci, and Dennis Hernandez are also acknowledged for their efforts obtaining genotypic resistance data on samples from the patients infected with GT-6g. Medical writing assistance was provided by Andrew Street of Articulate Science Ltd, funded by BMS. Publisher Copyright: {\textcopyright} 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.",

year = "2017",

month = dec,

doi = "10.1111/jgh.13796",

language = "English",

volume = "32",

pages = "1998--2005",

journal = "Journal of Gastroenterology and Hepatology (Australia)",

issn = "0815-9319",

publisher = "Wiley-Blackwell",

number = "12",

}

Kao, JH, Yu, ML, Peng, CY, Heo, J, Chu, CJ, Chang, TT, Lee, YJ, Hu, TH, Yoon, KT, Paik, SW, Lim, YS, Ahn, SH, Isakov, V, McPhee, F, Hu, W, Scott Swenson, E, Yin, PD & Treitel, M 2017, 'Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1', Journal of Gastroenterology and Hepatology (Australia), vol. 32, no. 12, pp. 1998-2005. https://doi.org/10.1111/jgh.13796

TY - JOUR

T1 - Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1

AU - Kao, Jia Horng

AU - Yu, Ming Lung

AU - Peng, Cheng Yuan

AU - Heo, Jeong

AU - Chu, Chi Jen

AU - Chang, Ting Tsung

AU - Lee, Youn Jae

AU - Hu, Tsung Hui

AU - Yoon, Ki Tae

AU - Paik, Seung Woon

AU - Lim, Young Suk

AU - Ahn, Sang Hoon

AU - Isakov, Vasily

AU - McPhee, Fiona

AU - Hu, Wenhua

AU - Scott Swenson, Eugene

AU - Yin, Philip D.

AU - Treitel, Michelle

N1 - Funding Information: The authors thank the patients and their families, study investigators, and site personnel for their participation. The study was funded, designed, and conducted by the sponsor (BMS) in collaboration with the principal investigators. The sponsor collected the data, monitored the study conduct, and performed the statistical analysis. Joseph Ueland, Vincent Vellucci, and Dennis Hernandez are also acknowledged for their efforts obtaining genotypic resistance data on samples from the patients infected with GT-6g. Medical writing assistance was provided by Andrew Street of Articulate Science Ltd, funded by BMS. Publisher Copyright: © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

PY - 2017/12

Y1 - 2017/12

N2 - Background and Aim: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis. Methods: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n = 138) or treatment-experienced (n = 31), received twice-daily DCV-TRIO for 12 weeks with 24 weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients. Results: Eighty-eight (52%) patients were men, 81 (48%) Taiwanese, 78 (46%) Korean, and 10 (6%) Russian; 23 (14%) had compensated cirrhosis, and 52 (31%) were IL28B (rs1297860) non-CC genotype. Baseline resistance-associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15%) patients with available genotype-1 sequencing data. SVR12 was achieved by 98.6% (136/138; 95% confidence interval: 94.9–99.8%) of treatment-naive and 100% (31/31; 95% confidence interval: 88.8–100%) of treatment-experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype-6g; 100% SVR12 was observed for genotype-1a (n = 8) and genotype-1b (n = 157). Two patients experienced serious adverse events. Eight (5%) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2%); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths. Conclusions: Twelve weeks of DCV-TRIO was well tolerated and provided 100% SVR12 in treatment-naive and treatment-experienced patients with genotype-1 infection, with or without cirrhosis, including those with baseline NS5A-L31 or NS5A-Y93 resistance-associated substitutions.

AB - Background and Aim: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis. Methods: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n = 138) or treatment-experienced (n = 31), received twice-daily DCV-TRIO for 12 weeks with 24 weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients. Results: Eighty-eight (52%) patients were men, 81 (48%) Taiwanese, 78 (46%) Korean, and 10 (6%) Russian; 23 (14%) had compensated cirrhosis, and 52 (31%) were IL28B (rs1297860) non-CC genotype. Baseline resistance-associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15%) patients with available genotype-1 sequencing data. SVR12 was achieved by 98.6% (136/138; 95% confidence interval: 94.9–99.8%) of treatment-naive and 100% (31/31; 95% confidence interval: 88.8–100%) of treatment-experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype-6g; 100% SVR12 was observed for genotype-1a (n = 8) and genotype-1b (n = 157). Two patients experienced serious adverse events. Eight (5%) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2%); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths. Conclusions: Twelve weeks of DCV-TRIO was well tolerated and provided 100% SVR12 in treatment-naive and treatment-experienced patients with genotype-1 infection, with or without cirrhosis, including those with baseline NS5A-L31 or NS5A-Y93 resistance-associated substitutions.

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Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1

Abstract

Bibliographical note

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UN SDGs

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