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.
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