An interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the nonnucleoside polymerase inhibitor ABT-333, and ribavirin showed efficacy against the hepatitis C virus (HCV) in a pilot study involving patients with HCV genotype 1 infection.
The addition of another potent agent, the NS5A inhibitor ABT-267, may improve efficacy, especially in difficult-to-treat patients.
Dr Kris Kowdley and colleagues evaluated multiple regimens of direct-acting antiviral agents and ribavirin in patients with HCV genotype 1 infection.
The patients had not received therapy previously or who had no response to prior therapy with pegylated interferon and ribavirin.
The team performed a phase 2b, open-label study with 14 treatment subgroups of 571 patients without cirrhosis who had not received treatment previously or who had not had a response to prior therapy.
The patients were randomly assigned to a regimen of ABT-450/r, combined with ABT-267 or ABT-333 or both, for 8, 12, or 24 weeks and received at least one dose of therapy.
All the subgroups but 1 also received ribavirin.
|Sustained virologic response across all treatment subgroups ranged from 83 to 100%|
|New England Journal of Medicine|
The team's primary end point was sustained virologic response at 24 weeks after the end of treatment.
The primary efficacy analysis compared rates between previously untreated patients who received three direct-acting antiviral agents and ribavirin for 8 weeks and those who received the same therapy for 12 weeks.
The research team found that among previously untreated patients who received 3 direct-acting antiviral agents plus ribavirin, the rate of sustained virologic response at 24 weeks after treatment was 88% among those who received the therapy for 8 weeks, and 95% among those who received the therapy for 12 weeks.
The rates of sustained virologic response across all treatment subgroups ranged from 83 to 100%.
The team observed that the most frequent adverse events were fatigue, headache, nausea, and insomnia.
The team noted that 1% of patients discontinued treatment owing to adverse events.
Dr Kowdley's team concludes, "In this phase 2b study, all-oral regimens of antiviral agents and ribavirin were effective both in patients with HCV genotype 1 infection who had not received therapy previously, and in those who had not had a response to prior therapy."