Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b–infected null responders

Abstract

Patients with chronic hepatitis C virus (HCV) infection and previous null response to pegylated interferon (Peg‐IFN) and ribavirin (RBV) 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 IIa study included 10 patients with chronic HCV genotype 1b infection and previous null response (10 reduction in HCV RNA after 12 weeks) to Peg‐IFN and RBV. Patients received dual DAA treatment for 24 weeks with the nonstructural protein 5A replication complex inhibitor, daclatasvir (60 mg once‐daily), and the nonstructural protein 3 protease inhibitor, asunaprevir (initially 600 mg twice‐daily, then subsequently reduced to 200 mg twice‐daily). The primary efficacy endpoint was the proportion of patients with sustained virologic response (SVR) at 12 weeks post‐treatment (SVR₁₂). Nine patients completed 24 weeks of treatment; 1 patient discontinued treatment after 2 weeks. In the 9 patients who completed the full course of treatment, HCV RNA was undetectable at week 8 and remained undetectable through the end of treatment; all 9 patients achieved SVR₁₂ and SVR₂₄. 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 3 patients, but did not result in discontinuation. Conclusions: Dual therapy with daclatasvir and asunaprevir, without Peg‐IFN and RBV, can achieve high SVR rates in difficult‐to‐treat patients with HCV genotype 1b infection and previous null response to Peg‐IFN and RBV. (HEPATOLOGY 2011)