Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 1 hepatitis C virus infection with and without cirrhosis

Kazuaki Chayama, Fumitaka Suzuki, Yoshiyasu Karino, Yoshiiku Kawakami, Ken Sato, Tomofumi Atarashi, Atsushi Naganuma, Tsunamasa Watanabe, Yuichiro Eguchi, Hitoshi Yoshiji, Masataka Seike, Yoshiyuki Takei, Koji Kato, Katia Alves, Margaret Burroughs, Rebecca Redman, David L Pugatch, Tami J Pilot-Matias, Preethi Krishnan, Rajneet K Oberoi, Wangang Xie, Hiromitsu Kumada, Kazuaki Chayama, Fumitaka Suzuki, Yoshiyasu Karino, Yoshiiku Kawakami, Ken Sato, Tomofumi Atarashi, Atsushi Naganuma, Tsunamasa Watanabe, Yuichiro Eguchi, Hitoshi Yoshiji, Masataka Seike, Yoshiyuki Takei, Koji Kato, Katia Alves, Margaret Burroughs, Rebecca Redman, David L Pugatch, Tami J Pilot-Matias, Preethi Krishnan, Rajneet K Oberoi, Wangang Xie, Hiromitsu Kumada

Abstract

Background: The once-daily, all oral, RBV-free, pangenotypic direct-acting anti-viral regimen consisting of co-formulated NS3/4A protease inhibitor glecaprevir and NS5A inhibitor pibrentasvir (G/P), demonstrated high rates of sustained virologic response (SVR) in phase 2 and 3 studies outside Japan.

Methods: CERTAIN-1 is a phase 3, open-label, multicenter study assessing the safety and efficacy of G/P (300/120 mg) once daily in Japanese patients with chronic HCV GT1 infection. Patients without cirrhosis received 8 weeks of G/P or 12 weeks of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r, 25/150/100 mg); patients with cirrhosis received G/P for 12 weeks. The primary efficacy endpoint was non-inferiority of G/P compared to OBV/PTV/r by assessing SVR at post-treatment week 12 (SVR12) among non-cirrhotic patients without the NS5A Y93H polymorphism.

Results: SVR12 was achieved by 128/129 (99.2%; one patient lost to follow-up) non-cirrhotic patients in the 8-week G/P Arm (including 23/23 patients with the NS5A Y93H polymorphism) and 52/52 (100%) patients in the 12-week OBV/PTV/r Arm. No patients from the G/P Arm prematurely discontinued the study drug or experienced a treatment-emergent serious adverse event (TESAE). Three patients from the OBV/PTV/r Arm experienced five TESAEs and one of these patients discontinued the study drug due to TESAEs. All 38 (100%) patients with compensated cirrhosis achieved SVR12; in this group, no TESAEs were reported and one patient discontinued treatment due to an AE.

Conclusions: CERTAIN-1 study results demonstrate high efficacy and favorable tolerability of G/P in GT1-infected Japanese patients including those with the NS5A Y93H polymorphism, with no virologic failures observed.

Keywords: Direct-acting antivirals; Glecaprevir/pibrentasvir; Hepatitis C virus.

Conflict of interest statement

K Chayama: receives payment for lectures from MSD, AbbVie, BMS, Ajinomoto Pharmaceuticals Co., Ltd., Abbott, Astellas Phama Inc., Chugai Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Gilead, Mitsubishi Tanabe Pharma; received research funding from Ajinomoto Pharmaceuticals Co., Ltd., AbbVie, MSD, EA Pharma Co., Ltd., Toray Industries, Inc., Otsuka Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Mitsubishi Tanabe Pharma, Chugai Pharmaceutical Co., Ltd., BMS, Roche Diagnostics K.K., Janssen Pharmaceutical K.K. F Suzuki: received payment for lectures from AbbVie, Gilead, and BMS. Y Karino: received payment for lectures from AbbVie, BMS, MSD. K Sato: received research funding from AbbVie and MSD. T Atarashi: received payment for research funding from AbbVie. Y Takei: receives payment for lectures from MSD, Otsuka Pharmaceutical, Lundbeck, Nippon Shinyaku, BMS, Sumitomo Dainippon Pharma; received research funding from BMS, Otsuka Pharmaceutical, Eisai, Takeda Pharmaceutical, Sumitomo Dainippon Pharma, MSD, AbbVie, Daiichi-Sankyo. H Kumada: received payment for lectures from AbbVie, MDS, Gilead, Sumitomo Dainippon Pharma Co. Ltd, and BMS. K Kato, D Pugatch, R Redman, K Alves, T Pilot-Matias, P Krishnan, R K Oberoi, M Burroughs, W Xie: Employees of AbbVie; may hold AbbVie stock or options. The other authors declare that they no conflict of interest.

Figures

Fig. 1
Fig. 1
Study design for GT1-infected DAA-naïve patients enrolled and treated in the CERTAIN-1 study (Arm C included other patient cohorts reported elsewhere)
Fig. 2
Fig. 2
SVR12 rates for each arm in the ITT-PS, ITT and mITT populations. The error bars represent the 95% confidence intervals based on Wilson’s score method.  Arm A: 8-week G/P treatment; Arm B: 12-week OBV/PTV/r treatment; Arm C: 12-week G/P treatment. SVR sustained virologic response; ITT intent-to-treat; ITT-PS ITT population excluding patients with the NS5A Y93H baseline polymorphism; mITT ITT excluding patients who did not achieve SVR12 for reasons other than virologic failure

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