Source Hiroshima University, Hiroshima, Japan. chayama@hiroshima-u.ac.jp.

Patients with chronic hepatitis C virus (HCV) infection and prior null response to peginterferon and ribavirin have limited therapeutic options. HCV genotype 1 is the most common worldwide and the most difficult to treat; genotype 1b is the most common subtype of genotype 1 outside North America. The enhanced antiviral activity achieved by combining two direct-acting antiviral (DAA) agents may improve clinical outcomes. This open-label, phase 2a study included ten patients with chronic HCV genotype 1b infection and prior null response (<2 log(10) reduction in HCV RNA after 12 weeks) to peginterferon and ribavirin.

Patients received dual DAA treatment for 24 weeks with the NS5A replication complex inhibitor BMS-790052 (60 mg once daily) and the NS3 protease inhibitor BMS-650032 (initially 600 mg twice daily, subsequently reduced to 200 mg twice daily). The primary efficacy endpoint was the proportion of patients with sustained virologic response at 12 weeks post-treatment (SVR(12) ). Nine patients completed 24 weeks of treatment; one patient discontinued treatment after 2 weeks.

In the nine patients who completed the full course of treatment, HCV RNA was undetectable at week 8 and remained undetectable through the end of treatment; all nine patients achieved SVR(12) and SVR(24) . HCV RNA also remained undetectable post-treatment in the patient who discontinued after 2 weeks. There was no viral breakthrough. Diarrhea and headache, generally mild, were the most common adverse events; transaminase elevations were reported in three patients but did not result in discontinuation.

CONCLUSIONS: Dual therapy with BMS-790052 and BMS-650032, without peginterferon and ribavirin, can achieve high SVR rates in difficult-to-treat patients with hepatitis C virus genotype 1b infection and prior null response to peginterferon and ribavirin.