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

Abstract

BackgroundThe 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.MethodsCERTAIN-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.ResultsSVR12 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.ConclusionsCERTAIN-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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-017-1391-5) contains supplementary material, which is available to authorized users.

Efficacy and safety of elbasvir/grazoprevir for Japanese patients with genotype 1b chronic hepatitis C complicated by chronic kidney disease, including those undergoing hemodialysis: A post hoc analysis of a multicenter study

“…Considering the metabolism and excretion of these DAAs, it is presumed that they can be administered to patients with CKD. A phase 3 trial of glecaprevir/pibrentasvir demonstrated the high efficacy and safety in patients with CKD and those undergoing hemodialysis . IFN/ribavirin‐free, glecaprevir/pibrentasvir for pan‐genotype chronic hepatitis C patients is expected to treat genotype 2–6 chronic hepatitis C patients with CKD including hemodialysis, with high efficacy and safety.…”

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

“…Eight weeks of the daily fixed‐dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) gained FDA approval for use in treatment‐naive or interferon‐experienced adolescents aged ≥ 12 years or weighing ≥ 45 kg with any HCV genotype infection, without cirrhosis or with compensated cirrhosis (Child‐Pugh A). Although the registration trial included only adolescents with genotype 1‐4, glecaprevir/pibrentasvir garnered FDA approval for all genotypes based on the safety and efficacy of the regimen demonstrated in adults . The recommendations for use of glecaprevir/pibrentasvir in treatment‐experienced adolescents are also based on clinical trial data from adults .…”

Advanced liver fibrosis effects on the response to sofosbuvir‐based antiviral therapies for chronic hepatitis C

“…Subsequently, sofosbuvir plus ledipasvir (SOF + LDV), ombitasvir, paritaprevir plus ritonavir (OMV + PTV + r), and elbasvir plus grazoprevir (EBV + GPV), DCV + ASV plus beclabuvir therapies, and sofosbuvir plus ribavirin (SOF + RBV), OMV + PTV +r plus RBV, SOF + LDV therapies have become available for clinical use for genotypes 1 and 2 HCV‐infected patients, respectively. In 2017, the combination therapy with the NS3/4A inhibitor glecaprevir and the NS5A inhibitor pibrentasvir was approved for the pan‐genotypic treatment of HCV‐infected patients . Although the antiviral effect was drastically improved by the introduction of these DAA therapies, a small minority of patients remains unable to achieve viral eradication.…”