Twelve‐week ravidasvir plus ritonavir‐boosted danoprevir and ribavirin for non‐cirrhotic HCV genotype 1 patients: A phase 2 study

Abstract

The need for all-oral HCV treatments with higher response rates, improved tolerability and lower pill burden compared to interferon-inclusive regimen has led to the development of new direct-acting antiviral agents (DAAs). Ravidasvir (RDV) is a second-generation, pan-genotypic NS5A inhibitor with high barrier to resistance. The aim of this phase 2 study (EVERST study) was to assess the efficacy and safety of interferon-free, 12-week RDV plus ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimen for treatment-naïve Asian HCV genotype 1 (GT1) patients without cirrhosis. A total of 38 treatment-naïve, non-cirrhotic adult HCV GT1 patients were enrolled in this multi-center, open-label, single-arm phase 2 study (NCT03020095). All patients received a combination of RDV 200mg once daily (QD) plus DNVr 100mg/100mg twice daily (BID) and oral ribavirin 1000/1200 mg/day (bodyweight<75/≥75 kg) for 12 weeks. The primary endpoint was the rate of sustained virologic response 12 weeks after the end of treatment (SVR12). Of 38 patients, all (100%) achieved SVR12. During the study, no treatment-related serious adverse events, no patients discontinued treatment due to adverse events and no deaths were reported. Six of 37 (16%) patients with available sequences had HCV NS5A resistance-associated variants (NS5A RAVs) at baseline. All patients (6/6) with baseline NS5A RAVs achieved SVR12. Twelve-week RDV and DNVr in combination with ribavirin for 12 weeks achieves the SVR12 rate of 100% in treatment-naïve non-cirrhotic Asian patients with HCV GT1 infection. This interferon-free regimen is also safe and well tolerated.