Mericitabine and ritonavir‐boosted danoprevir with or without ribavirin in treatment‐naive HCV genotype 1 patients: INFORM‐SVR study. (19th June 2014) - Gane, Edward J.
Abstract Background & Aims Safety and tolerability of peginterferon‐based hepatitis C virus (HCV) infection therapy remains suboptimal, even when direct‐acting antiviral agents are added. This study assessed the efficacy, safety and tolerability of mericitabine combined with ritonavir‐boosted danoprevir (danoprevir/r) ± ribavirin for up to 24 weeks in treatment‐naïve HCV genotype (G)1 infected patients. Methods Patients received twice daily mericitabine (1000 mg) and danoprevir/r (100 mg/100 mg) plus either ribavirin (1000/1200 mg/day; Arm A) or placebo (Arm B) for 12 or 24 weeks. Patients with HCV RNA <43 IU/ml between Weeks 2 and 8 and HCV RNA <15 IU/ml at Week 10 were rerandomized (1:1) at Week 12 to discontinue/continue assigned regimens until Week 24. Because of unacceptable relapse rates in both 12‐week arms and in ribavirin‐free Arm B, treatment was extended to 24 weeks and patients in Arm B received peginterferon alfa‐2a/ribavirin. The primary outcome was sustained virological response 24 weeks after end of treatment (SVR24). Results In Arm A, the SVR24 rate in patients receiving 24 weeks of therapy was 37.9% (25/66); 63.6% (14/22) in G1b and 25.0% (11/44) in G1a patients. Virologic breakthrough and relapse were associated with danoprevir‐resistant virus in most cases. The mericitabine‐resistance mutation (NS5BS282T) was detected in two patients bearing dual resistant virus NS3 R155K/NS5B S282T and dual resistance mutation L159F/L320F in one patient. Treatment was safe and well tolerated. Conclusions Mericitabine, danoprevir/r plus ribavirin for 24 weeks were safe and well tolerated. However, SVR rates were poor, achieving rates of only 25.0% in G1a and 63.6% in G1b patients.