There is a need for Interferon-free treatment regimens for hepatitis C virus ( HCV ) infection. The goal of a study was to evaluate ABT-450, a potent HCV NS3 protease inhibitor, combined with low-dose Ritonavir ( ABT-450/r ), in addition to ABT-333, a nonnucleoside NS5B polymerase inhibitor, and Ribavirin, for the treatment of HCV infection.
Researchers have conducted a 12-week, phase 2a, open-label study involving patients who had HCV genotype 1 infection without cirrhosis.
All patients received ABT-333 ( 400 mg twice daily ) and Ribavirin ( 1000 to 1200 mg per day ) and one of two daily doses of ABT-450/r.
Groups 1 and 2 included previously untreated patients; group 1 received 250 mg of ABT-450 and 100 mg of Ritonavir, and group 2 received 150 mg and 100 mg, respectively.
Group 3, which included patients who had had a null or partial response to previous therapy with Peginterferon and Ribavirin, received daily doses of 150 mg of ABT-450 and 100 mg of Ritonavir.
The primary end point was an undetectable level of HCV RNA from week 4 through week 12 ( extended rapid virologic response ).
A total of 17 of the 19 patients in group 1 ( 89% ) and 11 of the 14 in group 2 ( 79% ) had an extended rapid virologic response; a sustained virologic response 12 weeks after the end of treatment was achieved in 95% and 93% of the patients, respectively.
In group 3, 10 of 17 patients ( 59% ) had an extended rapid virologic response, and 8 ( 47% ) had a sustained virologic response 12 weeks after therapy; 6 patients had virologic breakthrough, and 3 had a relapse.
Adverse events included abnormalities in liver-function tests, fatigue, nausea, headache, dizziness, insomnia, pruritus, rash, and vomiting.
In conclusion, this preliminary study suggests that 12 weeks of therapy with a combination of a protease inhibitor, a nonnucleoside polymerase inhibitor, and Ribavirin may be effective for treatment of HCV genotype 1 infection. ( Xagena )
Poordad F et al, N Engl J Med 2013; 368:45-53