12-Week Interferon-Free Regimen of ABT-450/r+ABT-333+Ribavirin Achieved SVR12 in More Than 90% of Treatment-Naïve HCV Genotype-1-Infected Subjects and 47% of Previous Non-Responders
Speaker: Fred Poordad
Author: F. Poordad1*, E. Lawitz2, K.V. Kowdley3, G.T. Everson4, B. Freilich5, D. Cohen6, S. Siggelkow6, M. Heckaman6, R. Menon6, T. Pilot-Matias6, T. Podsadecki6, B. Bernstein6
Affiliation: 1Cedars-Sinai Medical Center, Los Angeles, CA, 2Alamo Medical Research, San Antonio, TX, 3Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, 4University of Colorado Denver and Hospital, Aurora, CO, 5Kansas City Gastroenterology & Hepatology, Kansas City, MO, 6Abbott, Abbott Park, IL, USA. *fred.poordad@cshs.org
Background: ABT-450 is a potent NS3 HCV protease inhibitor identified as a lead compound by Abbott and Enanta (boosted with low-dose ritonavir, ABT-450/r), and ABT-333 is a non-nucleoside NS5B polymerase inhibitor. ABT-450/r and ABT-333 are being evaluated together, and in combination with other anti-HCV agents, for the treatment of HCV infection.
Methods: HCV genotype-1, non-cirrhotic subjects were enrolled in an open-label study of ABT-450/r QD + ABT-333 BID + weight-based ribavirin administered twice daily (1000-1200 mg total daily dose). Two different doses of ABT-450/r were evaluated in treatment-naïve subjects; treatment-experienced subjects were also assessed, as described in the table. Treatment duration was 12 weeks.
Results: Baseline demographics and virologic results are shown in the table. Eighty-eight percent of subjects were subtype 1a. One subject in Arm 1 discontinued due to isolated ALT/AST elevations at week 2, 1 subject in Arm 2 discontinued due to noncompliance during week 1. All remaining subjects in Arms 1 and 2 completed treatment and achieved SVR12. In Arm 3, 6 subjects experienced viral breakthrough while on treatment, and 3 subjects relapsed at post-treatment week 2. Forty-seven percent of subjects in Arm 3 achieved SVR12. Virologic responses appear to be independent of ABT-450/r dose and IL28B genotype in treatment-naïve subjects.
There were no deaths or serious adverse events (AEs). The most common AEs were fatigue (42%), nausea (22%), and headache (20%). Most AEs were mild or moderate; 4 subjects experienced severe AEs (fatigue, pain, hyperbilirubinemia [maximum value: 106 mcmol/L, 6.2 mg/dL], and vomiting); none resulted in study drug interruption or discontinuation.
Conclusions: In this study, an interferon-free 12-week regimen of ABT-450/r+ABT-333+RBV was well tolerated and achieved SVR12 in 93-95% of treatment-naïve and 47% of previous non-responder subjects infected with HCV genotype-1. ABT-450/r 250/100 mg and 150/100 mg doses show comparable efficacy in treatment-naïve subjects. The difference in SVR rates observed in naïve and previous non-responders suggest that extrapolation of results across these populations must be done with caution. Additional trials of ABT-450/r in 2 and 3 DAA regimens are currently underway.