EASL 2014 - CARE Liver Disease Faculty - Abstract O1: SAPPHIRE II

Phase 3 Placebo-Controlled Study Of Interferon-Free, 12-Week Regimen Of ABT-450/R/ABT-267, ABT-333, And Ribavirin In Treatment-Experienced Adults With Hepatitis C Virus Genotype 1

S. Zeuzem1, I. Jacobson2, T. Baykal3, R.T. Marinho4, F. Poordad5, M. Bourliere6, M. Sulkowski7, H. Wedemeyer8, E. Tam9, P. Desmond10, D. Jensen11, A.M. Di Bisceglie12, P. Varunok13, T. Hassanein14, J. Xiong3, B. DaSilva-Tillmann3, L. Larsen3, T. Podsadecki3

Background and Aims: Efficacy in retreatment of HCV-infected patients is associated with treatment history, with the lowest responses occurring among prior peginterferon/ribavirin null-responders. 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; ABT-333 is an NS5B RNA polymerase inhibitor. The safety and efficacy of ABT-450/r/ABT-267+ABT-333+RBV(3D+RBV) was evaluated among non-cirrhotic peginterferon/ribavirin-experienced, HCV genotype(GT)1-infected patients in an interferon-free phase III trial.

Results: 297 patients received 3D+RBV; 97 received matching placebos. The Arm A(3D+RBV active regimen) SVR12 rate was 96.3%(286/297). 2.4% of patients had virologic failure. SVR12 rates in prior peginterferon/ribavirin relapsers, partial-responders, and null-responders were 95.3%, 100%, and 95.2%, respectively. SVR12 rates were comparable among genotype 1a and 1b patients (96.0% and 96.7%, respectively).
The most common adverse events(AEs) in Arm A(3D+RBV active regimen) and Arm B(placebo) were headache(36.4% and 35.1%, respectively) and fatigue(33.3% and 22.7%, respectively); the frequency of these events did not differ significantly between arms(P>0.05). No moderate/severe AEs occurred significantly more frequently in Arm A vs. B(P>0.05). Rates of discontinuation due to AEs were 1.0% and 0% in Arm A(3D+RBV active regimen) and Arm B(placebo), respectively.

Conclusions: A multi-targeted antiviral approach combining ritonavir-boosted ABT-450, ABT-267, and ABT-333 with ribavirin achieves high SVR12 rates with low rates of treatment discontinuation in treatment-experienced non-cirrhotic HCV genotype 1-infected patients, including prior null-responders.

Figure 2.   Sustained Virologic Response in the Entire Active-Regimen Group and According to Hepatitis C Virus (HCV) Genotype

Figure 2. Sustained Virologic Response in the Entire Active-Regimen Group and According to Hepatitis C Virus (HCV) Genotype

The phase 3 SAPPHIRE-1 and -2 trials demonstrated high rates of sustained virologic response (96%) to Abbvie’s 12-week interferon-free (3D+RBV) regimen among non-cirrhotic, treatment-naïve and treatment-experienced patients with HCV genotype 1. Response rates did not differ by HCV subtype (1a vs. 1b) or prior treatment response (partial responder, relapser, vs. null responder), and an additional trial (TURQOISE-1; Poordad et al., EASL Abstract O163) revealed similarly encouraging results among patients with compensated cirrhosis (SVR12, 92%). This regimen was generally well tolerated although ribavirin-related side effects including hemolytic anemia (hemoglobin <100g/L in ~5%), and drug-drug interactions, including those attributable to ritonavir, will require consideration with the clinical use of this therapy.
— CARE Liver Disease Faculty Perspectives

1J.W. Goethe University, Frankfurt, Germany, 2Weill Cornell Medical College, New York, NY, 3AbbVie Inc., North Chicago, IL, United States, 4Centro Hospitalar de Lisboa Norte, Lisbon, Portugal, 5The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, United States, 6Hôpital Saint Joseph, Marseille, France, 7Johns Hopkins University, Baltimore, MD, United States, 8Medizinische Hochschule Hannover, Hannover, Germany, 9LAIR Centre, Vancouver, BC, Canada, 10St Vincent's Hospital (Melbourne), Fitzroy, VIC, Australia, 11Center for Liver Diseases, University of Chicago Medical Center Chicago, Chicago, IL, 12Saint Louis University, St. Louis, MO, 13Premier Medical Group of the Hudson Valley, PC, Poughkeepsie, NY, 14Southern California Liver Centers and Southern California Research Center, Coronado, CA, United States