Journal Article

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

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

2018

Overview

BackgroundOnce-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).MethodsThis 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).ResultsThe 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.ConclusionsG/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.

• Publisher: Springer Nature B.V
• Subject: Chronic infection / Cirrhosis / Glomerular filtration rate / Hemodialysis / Interferon / Kidneys / Liver cirrhosis / Oral administration / Patients / Ribonucleic acid / RNA