Marcellin et al. suggest that the rate of sustained virologic response 12 weeks posttreatment (SVR12), rather than SVR24, could be a reliable primary endpoint in trials of interferon (IFN)-based therapy for chronic hepatitis C virus (HCV) infection. To determine whether this is true for IFN-free regimens, we analyzed data from the SOUND-C2 trial, which investigated the IFN-free combination of the protease inhibitor faldaprevir (BI 201335) and the nonnucleoside polymerase inhibitor deleobuvir (BI 207127) in treatment-naïve patients with genotype-1 HCV. HCV RNA was measured 4, 12, 24, and 48 weeks posttreatment and concordance between SVR rates at different timepoints was calculated.
SVR12 rates were up to 69% in the overall population and 85% in genotype-1b patients without any relapses occurring between SVR12 and SVR24. The positive predictive value (PPV) of SVR12 for SVR24 was 100% in all study arms.
In preliminary analyses, only one patient of all 250 patients who achieved SVR12 relapsed between the SVR12 and SVR48 timepoints. The PPV of SVR12 for SVR48 was 98%-100%.
The relapsing patient was a 66-year-old white male without cirrhosis (IL28B non-CC), with HCV genotype-1b. HCV RNA was 6.4 log10 IU/mL at baseline and dropped below the limit of detection by Day 14. It remained undetectable until relapse was detected 48 weeks posttreatment (HCV RNA ∼5.4 log10 IU/mL). No adherence issues were reported and no mutations known to confer resistance to faldaprevir or deleobuvir were detected at baseline or time of relapse. The nucleotide sequences of the NS3 and NS5B regions in the baseline and relapse virus were >99% homologous, indicating relapse rather than reinfection.
Our results support SVR12 as a primary endpoint in IFN-free HCV trials. They also emphasize the importance of monitoring all patients for at least 1 year following the end of IFN-based or IFN-free treatment.
Stefan Zeuzem, M.D.1
Federico J. Mensa, M.D.2
1Klinikum der J. W. Goethe-Universität, Frankfurt am Main, Germany
2Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA