Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 2 hepatitis C virus infection with and without cirrhosis

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.

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

“…Additionally, there were no cases of hepatic decompensation, and no events consistent with drug-induced liver injury were reported. The low rates of laboratory abnormalities observed in this study were also observed in Japanese patients with GT 1 or 2 infection without cirrhosis and with compensated cirrhosis enrolled in the CERTAIN studies and treated with G/P (reported elsewhere [ 17 , 18 ]). Similar overall safety results were observed across all phase 2 and phase 3 studies conducted outside Japan.…”

“…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 HCV infection. Results from substudy 1 where HCV GT1-infected patients without cirrhosis were treated for 8 weeks with G/P or 12 weeks with ombitasvir/paritaprevir/ritonavir, as well as patients in substudy 2 with HCV GT1 and GT2 infection and compensated cirrhosis treated with G/P for 12 weeks have been reported elsewhere [ 17 , 18 ]. Here we report on the remainder of patients in substudy 2 who belong to four special populations: HCV GT1- or GT2-infected patients who failed prior DAA-treatment including patients with compensated cirrhosis, GT1 or GT2 HCV-infected patients with severe renal impairment and compensated cirrhosis, GT3 HCV-infected patients who were treatment-naive or IFN treatment-experienced, all of whom received treatment with G/P for 12 weeks, and patients with GT1 or GT2 HCV infection with severe renal impairment without cirrhosis who received treatment for 8 weeks.…”

Systematic review with meta‐analysis: impact of baseline resistance‐associated substitutions on the efficacy of glecaprevir/pibrentasvir among chronic hepatitis C patients

“…Seventeen studies fulfilled the eligibility criteria and were included in the analysis. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] The reasons for excluding the remaining studies are detailed in Figure 1.…”

“…Four studies compared the SVR12 rates in patients with prior DAA-failure, 20,27,32,36 nine studies reported efficacy in the presence of baseline RAS in patients withGT1 20,21,27,29,[31][32][33][34]36 and five studies reported the efficacy and baseline RAS in patients with GT3. 29,31,33,34,36 Six studies excluded cirrhotic patients, [25][26][27]29,31,33 three studies included patients with concomitant chronic kidney disease and HCV infection, 20,28,33 one study evaluated patients with HIV-HCV co-infection.…”

“…Fourteen studies reported the prevalence of baseline RAS in the treated patients and were included in the primary analysis. [20][21][22]24,25,[27][28][29][30][31][32][33][34]36 Two studies reported only the prevalence of baseline RAS polymorphisms, 26,35 while one did not report the baseline RAS prevalence in patients who failed the treatment. 23 In patients with baseline RAS, 97.0% achieved SVR12 compared to 99.6% in patients with no RAS (OR 0.32, 95% C.I [0.15, 0.65], I 2 = 0%) ( Figure 2A).…”