Comparison of Efficacy and Safety of Ombitasvir/Paritaprevir/ Ritonavir and Dasabuvir ± Ribavirin between Asian and Western HCV GT1b-Infected Patients

( Lai Wei ),( Yan Luo ),( Wang-long Chuang ),( Seung Woon Paik ),( Ming-lung Yu ),( Linda M Fredrick ),( Andrew Campbell ),( Roger Trinh ),( Jeffrey Enejosa ),( Nancy S Shulman ),( Jeong Heo ),( Nilou 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: ONYX-I and ONYX-II are Phase 3 studies exploring the PK, safety, and efficacy of the 3-DAA ± ribavirin regimen in a HCV GT1b-infected Asian population. Comparable PK exposures of the 3-DAA regimen between the Asian and predominantly Caucasian (thereafter referred to as “Western”) HCV GT1-infected patients in other studies have been published. Methods: We compared the safety/efficacy profiles of the 3-DAA regimen (+ ribavirin for patients with compensated cirrhosis) in Asian patients in ONYX-I and -II Phase 3 studies conducted in China, Taiwan, and South Korea with Western patients enrolled in PEARL-II (treatment-experienced), PEARL-III (treatment-naive), and TURQUOISE-II (compensated cirrhosis) Phase 3 studies conducted exclusively in North America, Europe, and Australia. Results: Among treatment-naive non-cirrhotic patients, sustained virologic response at post treatment week 12 (SVR12) was achieved by 99.5% (183/184; 95% CI 97.0-99.9) of Asian patients compared with 99.0% (207/209; 95% CI 97.7-100) of Western patients (GT1b). In non-cirrhotic treatment-experienced patients, SVR12 was achieved by 100% (141/141; 95% CI 97.4-100) of Asian patients and 100% (91/91; 95% CI 95.9-100) of Western patients (GT1b). Among cirrhotic patients, SVR12 was achieved by 100% (104/104; 95% CI 96.4-100) of Asian patients compared with 98.5% (67/68; 95% CI 95.3-100) of Western patients (GT1a and -1b-infected patients). The majority of Asian and Western patients with or without cirrhosis had at least 1 treatment-emergent adverse event (TEAE). A low percentage of Asian and Western patients (<4%) experienced serious TEAEs. TEAEs leading to treatment discontinuation, in both Asian and Western patients, were rare. No patients without cirrhosis and 1 subject with cirrhosis discontinued treatment due to a TEAE. Only 1 death occurred across the studies, which was not due to a TEAE. Conclusions: The safety/efficacy profiles were consistent between the Asian and Western HCV GT1b-infected patients treated with OBV+PTV/r + DSV.

Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir in Non-Cirrhotic Asian Patients with Genotype 1b HCV Infection: ONYX-I SVR24 Results

( Lai Wei ),( Jinlin Hou ),( Yan Luo ),( Jeong Heo ),( Chi-jen Chu ),( Zhongping Duan ),( Mong Cho ),( Jun Cheng ),( Jun Li ),( Jidong Jia ),( Wenjing Lu ),( Linda M Fredrick ),( Tami Pilot-matias ),( 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: HCV genotype 1b is the most common genotype in Asian patients. ONYX-I is a phase 3, randomised, double-blind, placebo-controlled study of the 3-DAA regimen of OBV/PTV/r and DSV in treatment- naive and treatment-experienced non-cirrhotic patients with HCV GT1b infection in China, South Korea and Taiwan. Methods: In this study, the safety/efficacy of OBV/PTV/r + DSV administered for 12 weeks were evaluated in non-cirrhotic Asian patients. Patients in Arm A received active study drug during a 12-week double-blind (DB) period, while patients in Arm B received placebo during the same period followed by an open-label (OL) period in which they received 12 weeks of active study drug. Efficacy was assessed by SVR12 and SVR24. Efficacy and safety were assessed in all patients who received at least one dose of active study drugs. Results: 650 HCV GT1b patients (54% female, 100% Asian, 44% treatment-experienced) were enrolled from China (n=410) South Korea (n=120) and Taiwan (n=120), and randomised 1:1 to Arms A and B. In Arm A, SVR12 and SVR24 rates were 99.5% (183/184) in treatment-naive patients and 100% (141/141) in treatment- experienced patients. Most treatment-emergent adverse events (TEAEs) in patients receiving the active drug were mild in severity. The most common (≥5%) TEAEs in Arm A were upper respiratory tract infection (10.5%), headache (6.2%) and dizziness (5.2%). Seven patients had serious AEs during active treatment (Arm A) and one patient in Arm A discontinued treatment. Conclusions: In non-cirrhotic Asian adults with HCV GT1b-infection, treated with OBV/PTV/r + DSV for 12 weeks, SVR24 rates equalled previously reported SVR12 rates from this study (99.5% of treatment- naive and 100% of treatment-experienced patients), and are consistent with other clinical trials with this drug combination. The treatment was generally well tolerated with mostly mild TEAEs reported.

Efficacy/Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with Ribavirin in Asian Patients with Genotype 1b HCV-Infected, Compensated Cirrhosis: ONYX-II SVR 24 Results

( Lai Wei ),( Gui-qiang Wang ),( Yan Luo ),( Chi-jen Chu ),( Seung Woon Paik ),( Jinlin Hou ),( Jun Cheng ),( Qing Xie ),( Zhongping Duan ),( Jia-horng Kao ),( Linda Fredrick ),( Bo Fu ),( Niloufar Mo 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: ONYX-II is a phase 3, open-label study of 3-DAA regimen of OBV/PTV/r and DSV with RBV in treatment-naive and experienced patients with genotype 1b HCV infection and compensated cirrhosis in China, South Korea and Taiwan. SVR12 rate was 100% and the favourable safety profile was shown. The present analysis reports efficacy( SVR24) and safety results. Methods: Patients with chronic GT1b HCV infection and compensated cirrhosis received OBV/PTV/r + DSV + RBV for 12 weeks and will be followed for 48 weeks post-treatment. Efficacy was assessed by SVR12 and SVR24. Safety was assessed as the percentage of patients wi th treatment-emergent adverse events (TEAEs) and laboratory evaluation. Results: Total of 104 patients with chronic GT1b HCV infection (62% female, 100% Asian, 58% treatment-experienced) were enrolled from China (n=63), South Korea (n=21) and Taiwan (n=20). All patients received at least one dose of study drugs. The SVR24 rate was 100% (concordant with SVR12), with no patient relapsing between post-treatment week 12 and 24. Most TEAEs were mild in severity. The most common TEAEs (≥10%) were increased blood bilirubin levels (25%), pruritus (15%), anaemia (14%), asthenia (12%), bilirubin conjugated increased (12%), blood bilirubin unconjugated increased (12%), dizziness (11%) and fatigue (11%). Four patients had serious AEs and all were assessed as not being related to the 3-DAA regimen (one was assessed as being possibly related to RBV). One patient discontinued treatment due to TEAEs (elevations in alanine aminotransferase [ALT], aspartate aminotransferase [AST] and blood bilirubin) after 3 weeks of dosing but achieved SVR12 and SVR24. Laboratory abnormalities ≥ grade 3 were infrequent (ALT: 3%; AST 2%; total bilirubin: 7%). No grade 3 haemoglobin decrease was reported. Conclusions: SVR24 and SVR12 rates were concordant (100%) in HCV GT1b-infected Asian patients with compensated cirrhosis. The regimen was generally well tolerated with mostly mild TEAEs reported.

Impact of Hepatoprotective Medications on the Safety and Efficacy of OBV/PTV/r plus DSV ± Ribavirin in HCV GT1b-infected Asian Patients

( Wan-long Chuang ),( Yan Luo ),( Jeong Heo ),( Gui-qing Wang ),( Ming-lung Yu ),( Yoon Jun Kim ),( Qing Xie ),( Cheng-yuan Peng ),( Mingxiang Zhang ),( Yan Huang ),( Wenjing Lu ),( Linda M. Fredrick 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Hepatoprotective medications (HPMs) are commonly used in patients with chronic liver disease, especially across Asia. The phase 3 ONYX-I and ONYX-II studies evaluated the safety and efficacy of the 3-DAA regimen of ombitasvir and paritaprevir/ritonavir (OBV/PTV/r) plus dasabuvir (DSV) ± ribavirin (RBV) in an exclusively HCV GT1b-infected Asian population. This post-hoc analysis evaluated the impact of HPM use in patients treated with OBV/PTV/r + DSV ± RBV in these studies. Methods: ONYX-I and ONYX-II enrolled patients in China, South Korea and Taiwan. SVR12, treatment-emergent adverse events (AEs), and alanine transaminase (ALT) normalization, as well as mean changes in ALT over time were assessed in patients using vs not using HPMs. HPM use defined as all medications administered during any treatment period. Results: Overall, 11% (36/325) of non-cirrhotic and 57% (59/104) of cirrhotic patients were receiving HPMs, with ursodeoxycholic acid being the most commonly used in both non-cirrhotic (5.2% [17/325]) and cirrhotic (14.4% [15/104]) patients. SVR12 rates were high (99.7- 100%) in both non-cirrhotic and cirrhotic patients irrespective of HPM use. The regimen was generally well tolerated, with low rates of SAEs and AEs leading to treatment discontinuation (Table). Of patients with ALT above normal at baseline (BL), 100% vs 95% of non-cirrhotic and 98% vs 89% of cirrhotic patients using or not using HPMs, respectively, had normal ALT values at end of treatment (EOT). Mean ALT levels during treatment declined rapidly and similarly with and without HPM use; mean changes from BL to EOT were -38.8 and -37.0 U/L, respectively, in non-cirrhotic and -54.2 and -66.6 U/L, respectively, in cirrhotic patients. Conclusions: OBV/PTV/r + DSV ± RBV achieved high SVR12 and was generally well tolerated regardless of HPM use. HPM use had no impact on the safety profile of OBV/PTV/r + DSV therapy in Asian HCV infected subjects.