Daclatasvir plus asunaprevir in treatment-naïve patients with hepatitis C virus genotype 1b infection

ARTICLE HIGHLIGHTS

Research background

Chronic hepatitis C virus (HCV) infection is a significant health burden across Asia, and affects 5-7 million people in China alone. Without effective treatment, patients can develop severe complications, such as cirrhosis or hepatocellular carcinoma. Previous therapies for the treatment of chronic HCV infection have been based on a combination of peg-interferon and ribavirin, both of which are associated with a high burden of adverse events (AEs) that contribute to poor treatment adherence and high rates of treatment discontinuations.

Research motivation

Daclatasvir plus asunaprevir (DUAL) is an all-oral combination of daclatasvir, an HCV NS5A inhibitor, and asunaprevir, an NS3 protease inhibitor. This regimen has previously demonstrated efficacy in several phase 3 studies of patients infected with HCV genotype 1b, including those characteristics known to attenuate response to interferon-based therapies. In this study, we sought to evaluate the efficacy and safety of DUAL in treatment-naïve patients from mainland China, South Korea and Russia.

Research objectives

The primary efficacy objective of the study was to measure the rate of sustained virologic response at posttreatment week 12 (SVR12) and to determine if this rate was significantly higher than the historical rate of 70% associated with peg-interferon plus ribavirin. Safety was monitored based on incidence of AEs and abnormalities in clinical laboratory assessments, vital signs and physical examinations.

Research methods

This was a phase 3, double-blind, placebo-controlled study of DUAL in treatment-naïve patients from mainland China, South Korea and Russia with chronic HCV genotype 1b infection. Patients were randomly assigned (3:1) to receive DUAL (daclatasvir 60 mg tablet once daily and asunaprevir 100 mg soft capsule twice daily) for 24 wk either immediately (immediate treatment arm) or after 12 wk of matching placebo (placebo-deferred treatment arm).

Research results

An SVR12 rate of 91.6% (95% confidence interval: 87.2-96.0) was observed among patients in the immediate treatment arm, which was significantly higher than the historical comparator rate (70%). SVR12 was largely unaffected by cirrhosis (89%), age ≥ 65 years (92%), male sex (90%), baseline HCV RNA ≥ 6 million (89%), or IL28B non-CC genotypes (96%), although SVR12 was higher among patients without (96%) than among those with (53%) baseline NS5A resistance-associated polymorphisms (at L31 or Y93H). DUAL was well tolerated during 24 wk of therapy in this study; the most common AEs (≥ 10% in the combined arms) were elevated alanine aminotransferase and upper respiratory tract infection. Two patients discontinued DUAL treatment; one due to aminotransferase elevations, nausea and jaundice and the other due to a fatality unrelated to treatment. There were no treatment-related deaths.

Research conclusions

This study demonstrates that the all-oral DUAL combination of daclatasvir plus asunaprevir was highly effective and well tolerated in treatment-naïve patients with HCV genotype 1b infection from mainland China, Russia and South Korea.

Research perspectives

These findings suggest that for patients in many Asian countries, such as China, where interferon-based combinations have been considered the standard of care for HCV infection, DUAL offers a more efficacious and tolerable alternative for the treatment of HCV genotype 1b infection, with an easier route of administration and shorter treatment duration.