Elbasvir/Grazoprevir (EBR/GZR) Does Not Worsen Renal Function in Patients with Hepatitis C Virus (HCV) Infection and Pre-Existing Renal Disease

( K. Rajender Reddy ),( David Roth ),( Annette Bruchfeld ),( Peggy Hwang ),( Barbara Haber ),( Bach-yen T. Nguyen ),( Eliav Barr ),( Janice Wahl ),( Wayne Greaves ),( Youngmi Eun ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Decreased estimated glomerular filtration rate (eGFR) has been reported in patients with HCV infection receiving direct-acting antiviral agents. EBR/GZR was safe and efficacious in patients with chronic kidney disease stage 4/5 (CKD 4/5) in the C-SURFER study. The aim of this analysis was to evaluate the impact of EBR/GZR on eGFR in patients with less severe CKD. Methods: We analyzed a pooled dataset of 1689 patients who received EBR/GZR (50 mg/100 mg) with or without ribavirin (RBV) for 8 (n=91, 5%), 12 (n=1238, 73%), 16 (n=211, 12%), or 18 (n=149, 9%) weeks (656 patients [39%] received RBV). Patients were treatment-naïve or treatment-experienced, and included cirrhotics and those with HIV co-infection. Creatinine values were assessed at baseline and ≥1 post-baseline timepoint. eGFR was calculated using the Modified Diet in Renal Disease equation at baseline, end of treatment, and 12 weeks post-therapy. Results: Of the 1689 patients evaluated, 32 had CKD 3 (eGFR < 60 mL/min/1.73 m2 to ≥30 mL/min/1.73 m2) and 1657 had eGFR >60 mL/min/1.73 m2 (Table). Demographics were similar in both groups except for a higher proportion of HIV-co-infected patients in the CKD 3 group (41% vs. 17%). Patients with CKD 3 and those with eGFR >60 mL/min/1.73 m2 at baseline did not show any decrease in eGFR during treatment or follow-up. Conclusions: EBR/GZR did not affect eGFR in patients with pre-existing eGFR >60 mL/min/1.73 m2 or those with CKD3. Treatment duration, RBV co-administration, cirrhosis, or HIV coinfection did not adversely affect renal outcome.

Safety and Efficacy of Elbasvir/Grazoprevir in Hepatitis C Virus (HCV) GT1-and GT4 infected Participants 65 Years and Older

( Steven L. Flamm ),( Cheng-yuan Peng ),( Oren Shibolet ),( Ronald Nahass ),( Peggy Hwang ),( Eliav Barr ),( Michael Robertson ),( Barbara Haber ),( Eungeol Sim ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Safety and efficacy of HCV therapy in older individuals is of growing importance as the population with HCV infection ages. The objectives of this study were to compare the safety and efficacy of elbasvir (EBR)/grazoprevir (GZR) in participants aged ≥65 and <65 years. Methods: Safety and efficacy data from participants with HCV genotype (GT)1 or 4 infection receiving EBR (50 mg/day)/GZR (100 mg/day) for 12 weeks in 12 clinical trials were pooled and analyzed according to age (≥65 years vs <65 years). Sustained virologic response (SVR) 12 was defined as HCV RNA <lower limit of quantification 12 weeks after end of treatment (COBAS ® AmpliPrep/COBAS® Taqman® v2.0). Results: In participants aged ≥65 years (n=339), mean age was 70 years (range, 65-82) versus 49 years (range, 18-64) in those <65 years (n=2139). Demographic parameters in participants aged ≥65 years versus <65 years were noncirrhotic (85% vs 83%), treatment-naive (72% vs 85%), HCV GT1 infection (99% vs 95%), male (44% vs 61%), and white (26% vs 59%), black (12% vs 13%), and Asian (61% vs. 26%) race, respectively. SVR12 rates were 323/339 (95.3%) and 2041/2139 (95.4%) in participants with HCV GT1 or 4 infection aged ≥65 and < 65 years, respectively (Table). Rates of serious adverse events (SAEs), discontinuations due to adverse events (AEs), drug-related SAEs, and deaths were similar in both age groups (Table). AEs (occurring in >5% of either age group) in participants aged ≥ 65 versus <65 years were headache (7.1% vs 13.0%), fatigue (6.8% vs 11.3%), nasopharyngitis (6.5% vs 4.9%), nausea (4.1% vs 7.2%), and diarrhea (3.5% vs 5.8%), respectively. Conclusions: The efficacy of EBR/GZR for 12 weeks was similar in participants aged ≥65 years versus those <65 years. Treatment was well tolerated in both age groups, with low rates of SAEs, discontinuations due to AEs, drug-related SAEs, and deaths.

An integrated analysis of elbasvir/grazoprevir in Korean patients with hepatitis C virus genotype 1b infection

Youn Jae Lee,Jeong Heo,Do Young Kim,Woo Jin Chung,Won Young Tak,Yoon Jun Kim4,백승운,Eungeol Sim,Susila Kulasingam,Rohit Talwani,Barbara Haber,Peggy Hwang 대한간학회 2019 Clinical and Molecular Hepatology(대한간학회지) Vol.25 No.4

Background/Aims: In the Republic of Korea, an estimated 231,000 individuals have chronic hepatitis C virus (HCV) infection. The aim of the present analysis was to evaluate the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) administered for 12 weeks in Korean patients who were enrolled in international clinical trial phase 3 studies. Methods: This was a retrospective, integrated analysis of data from patients with HCV genotype (GT) 1b infection enrolled at Korean study sites in four EBR/GZR phase 3 clinical trials. Patients were treatment-naive or had previously failed interferon-based HCV therapy, and included those with human immunodeficiency virus coinfection or Child- Pugh class A cirrhosis. All patients received EBR 50 mg/GZR 100 mg once daily for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after completion of therapy (SVR12, HCV RNA <15 IU/mL). Results: SVR12 was achieved by 73 of 74 (98.6%) patients. No patients had virologic failure and one discontinued from the study after withdrawing consent. SVR12 rates were uniformly high across all patient subgroups. A total of 16 patients had nonstructural protein 5A resistance-associated substitutions at baseline (16/73, 22%), all of whom achieved SVR12. Adverse events (AEs) reported in >5% of patients were fatigue (6.8%), upper respiratory tract infection (5.4%), headache (5.4%), and nausea (5.4%). Thirteen patients (17.6%) reported drug-related AEs, two serious AEs occurred, and two patients discontinued treatment owing to an AEs. Conclusions: In this retrospective analysis, EBR/GZR administered for 12 weeks was well-tolerated and highly effective in Korean patients with HCV GT1b infection.

Integrated Analysis of Elbasvir/Grazoprevir Clinical Trials in Korean Participants with Hepatitis C Virus Genotype 1b Infection

( Do Young Kim ),( Youn Jae Lee ),( Jeong Heo ),( Woo Jin Chung ),( Won Young Tak ),( Yoon Jun Kim ),( Seung Woon Paik ),( Eungeol Sim ),( Susila Kulasingam ),( Rohit Talwani ),( Barbara Haber ),( Peg 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: All-oral direct-acting antiviral medications have transformed the treatment of hepatitis C virus (HCV) infection; however, local evidence is limited in some regions, including Korea. We conducted an integrated analysis of the efficacy of elbasvir (EBR)/grazoprevir (GZR) in Korean participants with HCV infection enrolled in EBR/GZR phase 3 clinical studies. Methods: Participants with HCV GT1b infection enrolled at Korean study centers who received EBR/GZR 50 mg/100 mg for 12 weeks were included. The primary endpoint of all studies was sustained virologic response (HCV RNA < 15 IU/mL) 12 weeks after end of therapy (SVR12) in the full analysis set (all participants who received ≥1 dose of study medication). Results: A total of 74 Korean participants were included. Mean age was 55 years (SD, 11 years), 25 (33.8%) had cirrhosis, and 70 (94.6%) were treatment-naïve. There were no participants with HCV/HIV coinfection. SVR12 was achieved by 73 of 74 (98.6%) participants; and only 1 participant, who withdrew consent, failed to achieve SVR12. Therefore, in the modified full analysis set (excluding participants who discontinued for reasons unrelated to study medication), SVR12 was 100% (73/73). SVR remined high among participants with cirrhosis (25/25, 100%), baseline viral load >2,000,000 IU/mL (34/34 (100%), and age >65 years (16/16, 100%). Baseline NS5A resistance associated substitutions (RASs) were detected in 16 of 73 participants (22%) who had a treatment outcome of SVR or virologic failure; all 16 achieved SVR12. Rates of SVR12 among Korean participants in this analysis (73/74, 98.6%) were similar to those in non-Korean Asian participants with GT1b infection (378/388, 97.4%), and to non-Asian participants with GT1b infection (589/608, 96.9%) enrolled in phase 2/3 EBR/GZR clinical trials. Conclusions: The combination of EBR/GZR was highly effective in Korean participants with HCV GT1b infection, with high rates of SVR12 across all subgroups examined, including those with NS5A RASs.