Abstract
Background
Danoprevir (RG7227) is an inhibitor of the HCV NS3/4A protease. In two Phase Ib studies of treatment-naive patients with chronic HCV genotype 1 infection, danoprevir administration for 14 days was associated with HCV RNA median reduction reaching 3.8 log10 in monotherapy and 5.7 log10 in combination therapy with pegylated interferon (PEG-IFN)-α2a (40 KD) plus ribavirin (RBV). After the protocol-defined phase, patients were free to continue with PEG-IFN/RBV. Sustained virological response (SVR) was evaluated in patients who continued treatment with PEG-IFN/RBV.
Methods
Retrospective analysis of the patients who received a 14-day monotherapy regimen with danoprevir (100 or 200 mg every 8 or 12 h), or 14-day triple therapy with danoprevir (100, 200 or 300 mg every 8 h, or 400, 600 or 900 mg every 12 h) with PEG-IFN-α2a (40 KD; 180 mg/ week subcutaneously) and RBV (1,000–1,200 mg/day) followed by PEG-IFN-α2a (40 KD; 180 μg/week subcutaneously) and RBV (1,000–1,200 mg/day) for 46 weeks (triple therapy group) for a total of 48 weeks (monotherapy group).
Results
Data were collected from 15 patients with danoprevir monotherapy and 24 patients with danoprevir-based triple therapy. Virological results are expressed using an intention-to-treat principle. Premature treatment discontinuation occurred in five patients. Rapid virological response (RVR; week 4) rate was 50% and 69.6% and SVR rate was 60% and 70.8% in the mono-therapy and triple therapy groups, respectively. RVR was highly predictive of SVR (>90%; HCV RNA<15 IU/ml).
Conclusions
The addition of danoprevir for 14 days to PEG-IFN/RBV treatment results in a high SVR rate in HCV genotype 1 treatment-naive patients.