EASL 2014 - CARE Liver Disease Faculty - LBAO163: TURQUOISE-II

SVR12 Rates Of 92%-96% In 380 Hepatitis C Virus Genotype 1-Infected Adults With Compensated Cirrhosis Treated With ABT-450/R/ABT-267 And ABT-333 Plus Ribavirin (3d+RBV)

F. Poordad1, C. Hezode2, R. Trinh3, K.V. Kowdley4, S. Zeuzem5, K. Agarwal6, M.L. Shiffman7, H. Wedemeyer8, T. Berg9, E.M. Yoshida10, X. Forns11, S.S. Lovell3, B. Da Silva-Tillmann3, A.L. Campbell3, T. Podsadecki3

Background and Aims: ABT-450 is an HCV NS3/4A protease inhibitor (dosed with ritonavir 100mg, ABT-450/r) identified by AbbVie and Enanta. ABT-267 is an NS5A inhibitor, and ABT-333 is an NS5B RNA polymerase inhibitor. We report safety and efficacy of 3D+RBV in treatment-naïve and treatment-experienced adults with HCV genotype 1 infection and compensated cirrhosis.

Results: 380 subjects received 3D+RBV for 12 (Arm A, n=208) or 24 (Arm B, n=172) weeks. All primary endpoints were achieved. SVR12 rates were 91.8% and 95.9% in Arms A and B (intent-to-treat, Table); the difference between treatment arms was not statistically significant. The 3 most common adverse events in Arms A and B were fatigue (32.7% and 46.5%), headache (27.9% and 30.8%) and nausea (17.8% and 20.3%). Discontinuations due to adverse events were noted in approximately 2% of subjects.

Conclusions: In this first and to date, only, phase 3 study of an all-oral, interferon-free regimen exclusively in cirrhotic HCV genotype 1-infected patients, treatment with 3D+RBV resulted in high rates of SVR12 in both the 12- and 24-week treatment arms. The safety profile is consistent with results in non-cirrhotic populations using this regimen.

Table 1. Baseline Characteristics and Efficacy
For many practitioners, cirrhotic patients make up a large portion of their practice population and hence this study exclusively of cirrhotics with G1 HCV is important. Note, that while the inclusion criteria are broad (Alb>28, Plt>60, INR<2.3) this turned out to be a very compensated group with Childs score <6 and median albumin of 40, median platelet count of 140. All patients were Childs A. The results are promising, with SVR12 of 91.8% in the 12 week arm and 95.9% in the 24-week arm (no significant difference). Safety of the 3D+R regimen in this group was comparable to non-cirrhotics. Overall, this study increases our comfort in using this regimen in compensated cirrhotics and should form the basis for wide reimbursement of this regimen for these patients. However, to get to >98% SVR in all patient groups, this regimen is likely not potent enough and requires addition or substitution of one of the 3 DAAs in it. A follow-on study for which there is need is a safety/efficacy assessment in Childs B patients.
— CARE Liver Disease Faculty Perspectives

1The Texas Liver Institute/University of Texas Health Science Center, San Antonio, TX, United States, 2Henri Mondor Hospital, APHP, University Paris-Est, Inserm U955, Creteil, France, 3AbbVie Inc., North Chicago, IL, 4Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, United States, 5J.W. Goethe University, Frankfurt, Germany, 6Institute of Liver Studies, Kings College Hospital, London, United Kingdom, 8Liver Institute of Virginia, Newport News, VA, United States, 8Medizinische Hochschule Hannover, Hannover, 9Universitätsklinikum Leipzig, Leipzig, Germany, 10University of British Columbia, Vancouver, BC, Canada, 11Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, Barcelona, Spain