ABT-450/ritonavir (ABT-450/r) combined with pegylated interferon alpha-2a/ribavirin after 3-day monotherapy in genotype 1 (GT1) HCV-infected treatment-naïve subjects: 12-week sustained virologic
Speaker: E Lawitz
Author: E. Lawitz1*, F. Poordad2, E. DeJesus3, K. Kowdley4, I. Gaultier5, D. Cohen5, W. Xie5, L. Larsen5, T. Pilot-Matias5, R.M. Menon5, T. Podsadecki5, B. Bernstein5
Affiliation: 1Alamo Medical Research, San Antonio, TX, 2Cedars-Sinai Medical Center, Los Angeles, CA, 3Orlando Immunology Center, Orlando, FL, 4Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, 5Abbott, Abbott Park, IL, USA. *lawitz@alamomedicalresearch.com
Background: ABT-450, a potent NS3 HCV protease inhibitor identified as lead compound by Abbott and Enanta, is being developed for the treatment of HCV infection in combination with other anti-HCV agents. Co-administration of ABT-450 with low-dose ritonavir increases ABT-450 plasma concentrations and half-life, permitting once-daily dosing.
Methods: This ongoing, randomized, blinded dose-ranging study is assessing the safety and efficacy of ABT-450/r given alone for 3 days (dosed 50/100, 100/100, or 200/100 mg once-daily, or matching placebo), followed by combination with peginterferon alfa-2a 180 µg/week + weight-based ribavirin 1000-1200 mg/day (P/R) for 12 weeks. After week 12, subjects received P/R alone for 12-36 weeks and are followed post-treatment for 24 weeks. Subjects receiving ABT-450/r with undetectable HCV RNA from week 4 to week 12 were allowed to stop P/R on or after week 24. Eligibility criteria included HCV RNA level ≥100,000 IU/mL at screening and liver biopsy within 3 years consistent with HCV-induced liver damage, but no evidence of cirrhosis.
Results: Thirty-five subjects were randomized to ABT-450/r (n=24) or placebo (n=11): 10 (29%) were female, 6 (17%) black, and 11 (31%) Latino ethnicity. Baseline characteristics including mean age 50 years, mean BMI 27.3 kg/m2, mean HCV RNA 6.78 log10 IU/mL and 28 (80%) GT1a infection, were comparable across dose groups. There were no ABT-450/r-related serious or severe adverse events (AEs); AEs and laboratory abnormalities were generally similar in the placebo and ABT-450/r treatment groups, and consistent with the safety profile of P/R. Virologic responses are shown in the Table. SVR12 was achieved in 63%, 75% and 88% of subjects receiving P/R + ABT-450/r 50/100, 100/100 or 200/100 mg respectively, compared to 18% of placebo + P/R subjects.
Conclusions: ABT-450/r was well tolerated and demonstrated potent antiviral activity in treatment-naïve subjects when combined with P/R: SVR12 rates show an apparent dose response with similar safety profiles across all doses.