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 language | English |
|---|---|
| Pages (from-to) | 1-10 |
| Number of pages | 10 |
| Journal | Journal of Gastroenterology |
| DOIs | |
| Publication status | Accepted/In press - Oct 20 2017 |
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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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=85031921224&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85031921224&partnerID=8YFLogxK
U2 - 10.1007/s00535-017-1396-0
DO - 10.1007/s00535-017-1396-0
M3 - Article
C2 - 29052790
AN - SCOPUS:85031921224
SP - 1
EP - 10
JO - Journal of Gastroenterology
JF - Journal of Gastroenterology
SN - 0944-1174
ER -