Efficacy of 12 or 18 weeks of elbasvir plus grazoprevir with ribavirin in treatment‐naïve, noncirrhotic HCV genotype 3‐infected patients

Summary Elbasvir ( EBR ; HCV NS 5A inhibitor) and grazoprevir ( GZR ; HCV NS 3/4A protease inhibitor) are approved as a fixed‐dose combination to treat patients chronically infected with HCV genotypes 1 and 4. During the development programme and supported by in vitro potency, the efficacy of EBR + GZR was assessed in HCV GT 3‐infected patients. This study's aim was to determine the efficacy and tolerability of 12 or 18 weeks of EBR + GZR with ribavirin ( RBV ) in treatment‐naïve, noncirrhotic HCV GT 3‐infected patients. Randomized patients received open‐label EBR (50 mg once daily) + GZR (100 mg once daily) + RBV . The primary efficacy objective was to evaluate the sustained virologic response rates 12 weeks after the end of all study therapy ( SVR 12). SVR 12 rates (95% confidence interval) were 45.0% (23.1, 68.5) and 57.1% (34.0, 78.2) after treatment with EBR + GZR + RBV for 12 weeks or 18 weeks, respectively. On‐treatment virologic failure was observed in 41% (17 of 41) of patients. At virologic failure, resistance‐associated substitutions ( RAS s) with a >five‐fold shift in potency occurred in the NS 3 region in six (35%) patients and in the NS 5A region in 16 (94%) patients. The most common RAS at virologic failure was Y93H in NS 5A which was identified in 13 of 17 (76%) patients. The efficacy of EBR + GZR + RBV was suboptimal in HCV GT 3‐infected patients due to a high rate of on‐treatment virologic failure and treatment‐emergent RAS s which demonstrates an inadequate barrier to the development of GT 3 resistance. However, rapid viral clearance demonstrated the antiviral activity of EBR + GZR + RBV in GT 3‐infected patients.clinicaltrials.gov: NCT01717326.