Impact of Treatment Duration and Addition of Ribavirin on Real-World Effectiveness of Elbasvir/Grazoprevir: Retrospective Analyses from the Trio Network

( Eungeol Sim ),( Chizoba Nwankwo ),( Bruce Bacon ),( Michael P. Curry ),( Douglas T. Dieterich ),( Steven L. Flamm ),( Kris V. Kowdley ),( Scott Milligan ),( Naoky C. Tsai ),( Zobair M. Younossi ),( 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Lengthening treatment with elbasvir/grazoprevir (EBR/ GZR) to 16 weeks and/or adding ribavirin (RBV) is recommended for select patients with HCV GT1 infection. However, realworld data (J Hepatol 2017;66:S295) suggest that utilization of this regimen is low. This study examined the use of 12- and 16- week EBR/GZR ±RBV regimens in different patient subgroups. Methods: Data were collected from providers and specialty pharmacies through Trio Health’s disease management program. Patients (n=442) with HCV GT1 infection who initiated EBR/GZR therapy between Jan 28, 2016 (FDA approval) to Dec 31, 2016 were included. Results: 401 (91%) patients received EBR/GZR for 12 weeks, 12 (3%) received EBR/GZR+RBV for 12 weeks, 11 (2%) received EBR/GZR for 16 weeks, and 18 (4%) received EBR/GZR+RBV for 16 weeks. Possible baseline NS5A resistance was identified in 13/285 patients with GT1a infection: 3 (23%) received EBR/ GZR for 12 weeks, 1 (8%) received EBR/GZR+RBV for 12 weeks, 2 (15%) received EBR/GZR for 16 weeks, and 7 (54%) received EBR/GZR+RBV for 16 weeks. Across all patients, the +RBV subgroup had a higher proportion of treatment-experienced patients (43%, 13/30) than the -RBV group (17%, 69/412); and the 16-week subgroup had a higher proportion of GT1A subtype (93%, 27/29) than the 12-week group (62%, 258/413). Other characteristics including gender, age, baseline viral load, and cirrhosis were similar between regimens and between groups defined by RBV addition or therapy duration. SVR12 results at time of abstract submission were available for 262/442 patients. Overall per protocol (PP) SVR12 was 97% (253/262). Across GT1 subgroups (defined by subtype, prior treatment experience, and fibrosis) that received EBR/GZR for 12 weeks without RBV, the PP SVR12 was ≥94% (TABLE). Conclusions: In real-world practice, EBR/GZR was highly effective, with the majority of patients treated for 12 weeks without RBV. Full SVR12 data will be presented at the conference.

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.

Effectiveness of Elbasvir/Grazoprevir in Patients with Chronic Hepatitis C and Chronic Kidney Disease: Results from the Veterans Affairs System

( Jennifer R. Kramer ),( Amy Puenpatom ),( Kevin Erickson ),( Yumei Cao ),( Donna L. Smith ),( Eirum Chaudhri ),( Hashem B. El-serag ),( Fasiha Kanwal ),( Eungeol Sim ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Elbasvir/grazoprevir (EBR/GZR) is indicated for the treatment of chronic hepatitis C virus (HCV) genotype (GT) 1 and 4 infections and has demonstrated high sustained virologic response (SVR) in many HCV populations, including those with chronic kidney disease (CKD). The aim of this study was to evaluate the effectiveness of EBR/GZR in people with HCV infection and CKD in a real-world clinical setting. Methods: We conducted a nationwide retrospective observational cohort study of HCV-infected people in the US Department of Veterans Affairs (VA) using the VA Corporate Data Warehouse. The study population included people with RNA positive for HCV who initiated EBR/GZR between February 1 and December 1, 2016. Estimated glomerular filtration rate (eGFR), calculated per Kidney Disease Outcome Quality Initiative guidelines, was used to determine CKD stages. Results: A total of 2436 HCV-infected veterans treated with EBR/GZR ± ribavirin (RBV) were included in the evaluable population: 1611 (66.1%) had baseline eGFR >60 mL/min/1.73㎡, 393 (16.1%) had CKD stage 3 (eGFR, 30-59 mL/min/1.73㎡), and 407 (16.7%) had CKD stages 4-5 (eGFR < 30 mL/min/1.73㎡). The mean age was 63.5 years (SD=5.9). Most participants were male (96.5%), African American (57.4%), and had HCV genotype 1 infection (95.4%). Other comorbidities in these participants included cirrhosis (33.3%), diabetes (53.2%), depression (57.6%), and HIV infection (3.1%). 95.2% (1533/1611) of those with eGFR >60 mL/min/1.73㎡ achieved SVR. SVR rates were 96.7% in those with CKD stage 3, and 96.3% in those with CKD stages 4-5. SVR rates were 93.3-100% in participant subgroups based on HCV genotype, HIV coinfection, baseline viral load, and cirrhosis. Full SVR data will be presented at the meeting. Conclusions: EBR/GZR was highly effective in HCV-infected veterans with moderate to severe CKD. SVR rates were high across select subgroups in a large clinical setting.