Abstract

A 12-Week Interferon-Free Regimen of ABT-450/r, ABT-072, and Ribavirin was Well Tolerated and Achieved Sustained Virologic Response in 91% Treatment-Naïve HCV IL28B-CC Genotype-1-Infected Subject
Speaker: E Lawitz
Author: E. Lawitz1*, F. Poordad2, K.V. Kowdley3, D. Jensen4, D.E. Cohen5, S. Siggelkow5, K. Wikstrom5, L. Larsen5, R.M. Menon5, T. Podsadecki5, B. Bernstein5
Affiliation: 1Alamo Medical Research, San Antonio, TX, 2Cedars-Sinai Medical Center, Los Angeles, CA, 3Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, 4Center for Liver Diseases, University of Chicago Medical Center, Chicago, 5Abbott, Abbott Park, IL, USA. *lawitz@alamomedicalresearch.com
Background: ABT-450 is a potent NS3 HCV protease inhibitor identified as lead compound by Abbott and Enanta (dosed with low-dose ritonavir, ABT-450/r), and ABT-072 is a non-nucleoside NS5B polymerase inhibitor. Both are being developed for the treatment of HCV infection with other anti-HCV agents.
Methods: Eleven treatment-naïve, non-cirrhotic HCV Genotype-1 (GT-1) infected subjects with IL28B rs12979860 genotype CC were enrolled in an open-label study assessing the safety, tolerability, pharmacokinetics, and antiviral activity of ABT-450/r 150/100 mg once-daily (QD) + ABT-072 400 mg QD + weight-based ribavirin 1000-1200 mg/day dosed twice-daily for 12 weeks.
Results: Of the 11 subjects, 8 (73%) subjects were male, 9 (82%) Caucasian, and 3 (27%) reported Latino ethnicity. At baseline (BL), median age was 56 years (range 41-66), mean BMI was 26.9 kg/m2, and mean HCV RNA was 6.9 log10 IU/mL (100% with BL HCV RNA >800,000 IU/mL). Eight (73%) subjects were infected with GT1a. All 11 subjects completed 12 weeks of treatment and were followed for 24 weeks post-treatment. A rapid decrease in HCV RNA level was observed with treatment and all subjects had HCV RNA levels < 25 IU/mL by week 3 (Figure 1). All subjects maintained HCV RNA < 25 IU/mL from weeks 4 through 12 of treatment, and all had undetectable HCV RNA from week 5 to the end of treatment. One subject relapsed at post-treatment week 8, while 10 subjects (91%) achieved SVR24. Analysis of resistance variants in the subject who relapsed is currently being performed. There were no deaths, serious or severe adverse events (AEs), or premature discontinuations. Most reported AEs were mild in severity; the most common were headache, fatigue, nausea, and dry skin.
Conclusions: ABT-450/r + ABT-072 + RBV is well tolerated and achieves SVR24 in 91% of treatment-naïve, non-cirrhotic HCV GT1-infected subjects with IL28B CC genotype after 12 weeks of treatment.

Figure 1
[Figure 1]