Daclatasvir plus Peginterferon and Ribavirin is Non-inferior to Peginterferon and Ribavirin Alone, and Reduces Duration of Treatment for HCV Genotype 2 or 3 Infection: Chronic hepatitis C presenting with a diagnosis of hepatocellular carcinoma

BACKGROUND AND AIMS: Twenty-four weeks of treatment with peginterferon and ribavirin for chronic hepatitis C virus (HCV) genotype 2 or 3 infection produces a sustained virologic response (SVR) in 70%-80% of patients. We performed a randomized, double-blind, phase 2b study to assess whether adding daclatasvir, an NS5A inhibitor active against these genotypes, improves efficacy and shortens therapy.

METHODS: Patients with HCV genotype 2 or 3 infection (n=151), enrolled at research centers in North America, Europe, or Australia, were randomly assigned to groups given 12 or 16 weeks of daclatasvir (60 mg once daily), or 24 weeks of placebo, each combined with peginterferon alfa-2a and ribavirin. Treatment was extended to 24 weeks for recipients of daclatasvir who did not meet the criteria for early virologic response. The primary endpoint was sustained virological response 24 weeks after treatment (SVR24).

RESULTS: Baseline characteristics were similar among patients within each HCV genotype group. However, the 80 patients with HCV genotype 3, compared to the 71 patients with HCV genotype 2, were younger (mean, 45 vs 53 years old) and a larger proportion had cirrhosis (23% vs 1%). Among patients with HCV genotype 2 infection, an SVR24 was achieved by 83%, 83%, and 63% of those in the daclatasvir 12 week, daclatasvir 16 week, or placebo groups, respectively; among patients with HCV genotype 3 infection, an SVR24 was achieved by 69%, 67%, and 59% of patients in these groups. Differences between genotypes were largely attributable to the higher frequency of post-treatment relapse among patients infected with HCV genotype 3. In both daclatasvir arms for both HCV genotypes, the lower bound of the 80% confidence interval of the difference in SVR24 rates between the daclatasvir and placebo arms was above -20%, establishing non-inferiority. Safety findings were similar among groups, and typical of those expected from peginterferon alfa and ribavirin therapy.

CONCLUSIONS: Twelve or 16 weeks of treatment with daclatasvir, in combination with peginterferon alfa-2a and ribavirin, is well tolerated and effective therapy for patients with HCV genotype 2 or 3 infections. Daclatasvir-containing regimens could reduce the duration of therapy for these patients. Clinicaltrials.gov number: NCT01257204.