Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection

Hiromitsu Kumada, Tsunamasa Watanabe, Fumitaka Suzuki, Kenji Ikeda, Ken Sato, Hidenori Toyoda, Masanori Atsukawa, Akio Ido, Akinobu Takaki, Nobuyuki Enomoto, Koji Kato, Katia Alves, Margaret Burroughs, Rebecca Redman, David Pugatch, Tami J. Pilot-Matias, Preethi Krishnan, Rajneet K. Oberoi, Wangang Xie, Kazuaki Chayama

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Background: Once-daily, orally administered, co-formulated glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor) (G/P) demonstrated pangenotypic activity and high sustained virologic response (SVR) rates in studies outside Japan. Here we report safety and efficacy in a subset of Japanese patients with chronic HCV infection who received G/P 300/120 mg in a phase 3, open-label, multicenter study (CERTAIN-1). Methods: This analysis focuses on three difficult-to-treat subgroups: HCV GT1/2-infected patients who failed to achieve SVR after treatment with a direct acting antiviral (DAA)-containing regimen; GT1/2-infected patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2); and GT3-infected patients. Patients in the renal impairment and GT3 cohorts were treatment-naive or interferon treatment-experienced. Noncirrhotic GT1/2-infected, DAA-naïve patients in the renal impairment cohort received G/P for 8 weeks; all other patients were treated for 12 weeks. Primary outcome was SVR (HCV RNA < 15 IU/mL) 12 weeks post-treatment (SVR12). Results: The study enrolled 33 GT1/2-infected patients who failed previous DAA treatment (four with cirrhosis); 12 GT1/2-infected patients with severe renal impairment (two with cirrhosis); and 12 GT3-infected patients (two with cirrhosis). SVR12 was achieved by 31/33 (93.9%), 12/12 (100%), and 10/12 (83.3%) patients, respectively. One serious adverse event (fluid overload, not related to G/P) occurred in a patient on chronic intermittent hemodialysis. Conclusions: G/P achieved high SVR12 rates and was well tolerated in three difficult-to-treat patient subgroups with limited treatment options in Japan (DAA-experienced patients, patients with severe renal impairment, and GT3-infected patients). These results support the potential suitability of this regimen for these special populations in Japan.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalJournal of Gastroenterology
DOIs
Publication statusAccepted/In press - Oct 20 2017

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Antiviral Agents
Genotype
Kidney
Safety
Infection
Japan
Fibrosis
Therapeutics
Protease Inhibitors
Glomerular Filtration Rate
Interferons
Multicenter Studies
Renal Dialysis

Keywords

  • Cirrhosis
  • Glecaprevir
  • Pibrentasvir
  • Renal failure
  • Special population

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection. / Kumada, Hiromitsu; Watanabe, Tsunamasa; Suzuki, Fumitaka; Ikeda, Kenji; Sato, Ken; Toyoda, Hidenori; Atsukawa, Masanori; Ido, Akio; Takaki, Akinobu; Enomoto, Nobuyuki; Kato, Koji; Alves, Katia; Burroughs, Margaret; Redman, Rebecca; Pugatch, David; Pilot-Matias, Tami J.; Krishnan, Preethi; Oberoi, Rajneet K.; Xie, Wangang; Chayama, Kazuaki.

In: Journal of Gastroenterology, 20.10.2017, p. 1-10.

Research output: Contribution to journalArticle

Kumada, H, Watanabe, T, Suzuki, F, Ikeda, K, Sato, K, Toyoda, H, Atsukawa, M, Ido, A, Takaki, A, Enomoto, N, Kato, K, Alves, K, Burroughs, M, Redman, R, Pugatch, D, Pilot-Matias, TJ, Krishnan, P, Oberoi, RK, Xie, W & Chayama, K 2017, 'Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection', Journal of Gastroenterology, pp. 1-10. https://doi.org/10.1007/s00535-017-1396-0
Kumada, Hiromitsu ; Watanabe, Tsunamasa ; Suzuki, Fumitaka ; Ikeda, Kenji ; Sato, Ken ; Toyoda, Hidenori ; Atsukawa, Masanori ; Ido, Akio ; Takaki, Akinobu ; Enomoto, Nobuyuki ; Kato, Koji ; Alves, Katia ; Burroughs, Margaret ; Redman, Rebecca ; Pugatch, David ; Pilot-Matias, Tami J. ; Krishnan, Preethi ; Oberoi, Rajneet K. ; Xie, Wangang ; Chayama, Kazuaki. / Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection. In: Journal of Gastroenterology. 2017 ; pp. 1-10.
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abstract = "Background: Once-daily, orally administered, co-formulated glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor) (G/P) demonstrated pangenotypic activity and high sustained virologic response (SVR) rates in studies outside Japan. Here we report safety and efficacy in a subset of Japanese patients with chronic HCV infection who received G/P 300/120 mg in a phase 3, open-label, multicenter study (CERTAIN-1). Methods: This analysis focuses on three difficult-to-treat subgroups: HCV GT1/2-infected patients who failed to achieve SVR after treatment with a direct acting antiviral (DAA)-containing regimen; GT1/2-infected patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2); and GT3-infected patients. Patients in the renal impairment and GT3 cohorts were treatment-naive or interferon treatment-experienced. Noncirrhotic GT1/2-infected, DAA-na{\"i}ve patients in the renal impairment cohort received G/P for 8 weeks; all other patients were treated for 12 weeks. Primary outcome was SVR (HCV RNA < 15 IU/mL) 12 weeks post-treatment (SVR12). Results: The study enrolled 33 GT1/2-infected patients who failed previous DAA treatment (four with cirrhosis); 12 GT1/2-infected patients with severe renal impairment (two with cirrhosis); and 12 GT3-infected patients (two with cirrhosis). SVR12 was achieved by 31/33 (93.9{\%}), 12/12 (100{\%}), and 10/12 (83.3{\%}) patients, respectively. One serious adverse event (fluid overload, not related to G/P) occurred in a patient on chronic intermittent hemodialysis. Conclusions: G/P achieved high SVR12 rates and was well tolerated in three difficult-to-treat patient subgroups with limited treatment options in Japan (DAA-experienced patients, patients with severe renal impairment, and GT3-infected patients). These results support the potential suitability of this regimen for these special populations in Japan.",
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T1 - Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection

AU - Kumada, Hiromitsu

AU - Watanabe, Tsunamasa

AU - Suzuki, Fumitaka

AU - Ikeda, Kenji

AU - Sato, Ken

AU - Toyoda, Hidenori

AU - Atsukawa, Masanori

AU - Ido, Akio

AU - Takaki, Akinobu

AU - Enomoto, Nobuyuki

AU - Kato, Koji

AU - Alves, Katia

AU - Burroughs, Margaret

AU - Redman, Rebecca

AU - Pugatch, David

AU - Pilot-Matias, Tami J.

AU - Krishnan, Preethi

AU - Oberoi, Rajneet K.

AU - Xie, Wangang

AU - Chayama, Kazuaki

PY - 2017/10/20

Y1 - 2017/10/20

N2 - Background: Once-daily, orally administered, co-formulated glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor) (G/P) demonstrated pangenotypic activity and high sustained virologic response (SVR) rates in studies outside Japan. Here we report safety and efficacy in a subset of Japanese patients with chronic HCV infection who received G/P 300/120 mg in a phase 3, open-label, multicenter study (CERTAIN-1). Methods: This analysis focuses on three difficult-to-treat subgroups: HCV GT1/2-infected patients who failed to achieve SVR after treatment with a direct acting antiviral (DAA)-containing regimen; GT1/2-infected patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2); and GT3-infected patients. Patients in the renal impairment and GT3 cohorts were treatment-naive or interferon treatment-experienced. Noncirrhotic GT1/2-infected, DAA-naïve patients in the renal impairment cohort received G/P for 8 weeks; all other patients were treated for 12 weeks. Primary outcome was SVR (HCV RNA < 15 IU/mL) 12 weeks post-treatment (SVR12). Results: The study enrolled 33 GT1/2-infected patients who failed previous DAA treatment (four with cirrhosis); 12 GT1/2-infected patients with severe renal impairment (two with cirrhosis); and 12 GT3-infected patients (two with cirrhosis). SVR12 was achieved by 31/33 (93.9%), 12/12 (100%), and 10/12 (83.3%) patients, respectively. One serious adverse event (fluid overload, not related to G/P) occurred in a patient on chronic intermittent hemodialysis. Conclusions: G/P achieved high SVR12 rates and was well tolerated in three difficult-to-treat patient subgroups with limited treatment options in Japan (DAA-experienced patients, patients with severe renal impairment, and GT3-infected patients). These results support the potential suitability of this regimen for these special populations in Japan.

AB - Background: Once-daily, orally administered, co-formulated glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor) (G/P) demonstrated pangenotypic activity and high sustained virologic response (SVR) rates in studies outside Japan. Here we report safety and efficacy in a subset of Japanese patients with chronic HCV infection who received G/P 300/120 mg in a phase 3, open-label, multicenter study (CERTAIN-1). Methods: This analysis focuses on three difficult-to-treat subgroups: HCV GT1/2-infected patients who failed to achieve SVR after treatment with a direct acting antiviral (DAA)-containing regimen; GT1/2-infected patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2); and GT3-infected patients. Patients in the renal impairment and GT3 cohorts were treatment-naive or interferon treatment-experienced. Noncirrhotic GT1/2-infected, DAA-naïve patients in the renal impairment cohort received G/P for 8 weeks; all other patients were treated for 12 weeks. Primary outcome was SVR (HCV RNA < 15 IU/mL) 12 weeks post-treatment (SVR12). Results: The study enrolled 33 GT1/2-infected patients who failed previous DAA treatment (four with cirrhosis); 12 GT1/2-infected patients with severe renal impairment (two with cirrhosis); and 12 GT3-infected patients (two with cirrhosis). SVR12 was achieved by 31/33 (93.9%), 12/12 (100%), and 10/12 (83.3%) patients, respectively. One serious adverse event (fluid overload, not related to G/P) occurred in a patient on chronic intermittent hemodialysis. Conclusions: G/P achieved high SVR12 rates and was well tolerated in three difficult-to-treat patient subgroups with limited treatment options in Japan (DAA-experienced patients, patients with severe renal impairment, and GT3-infected patients). These results support the potential suitability of this regimen for these special populations in Japan.

KW - Cirrhosis

KW - Glecaprevir

KW - Pibrentasvir

KW - Renal failure

KW - Special population

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