Abstract and Introduction
Abstract
Genotype 2 hepatitis C virus (HCV) accounts for up to 30% of chronic HCV infections in Japan. The standard of care for patients with genotype 2 HCV – peginterferon and ribavirin for 24 weeks – is poorly tolerated, especially among older patients and those with advanced liver disease. We conducted a phase 3, open-label study to assess the efficacy and safety of an all-oral combination of the NS5B polymerase inhibitor sofosbuvir and ribavirin in patients with chronic genotype 2 HCV infection in Japan. We enrolled 90 treatment-naïve and 63 previously treated patients at 20 sites in Japan. All patients received sofosbuvir 400 mg plus ribavirin (weight-based dosing) for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after therapy (SVR12). Of the 153 patients enrolled and treated, 60% had HCV genotype 2a, 11% had cirrhosis, and 22% were over the aged 65 or older. Overall, 148 patients (97%) achieved SVR12. Of the 90 treatment-naïve patients, 88 (98%) achieved SVR12, and of the 63 previously treated patients, 60 (95%) achieved SVR12. The rate of SVR12 was 94% in patients with cirrhosis and in those aged 65 and older. No patients discontinued study treatment due to adverse events. The most common adverse events were nasopharyngitis, anaemia and headache. Twelve weeks of sofosbuvir and ribavirin resulted in high rates of SVR12 in treatment-naïve and previously treated patients with chronic genotype 2 HCV infection. The treatment was safe and well tolerated by patients, including the elderly and those with cirrhosis.
Introduction
Approximately two million people in Japan – nearly 2% of the population – are chronically infected with the hepatitis C virus (HCV). The population of patients with chronic HCV infection in Japan differs from that of other countries; patients are generally older, have more advanced liver disease and are more likely to have received previous treatment for HCV infection. It is estimated that 15–30% of Japanese patients with HCV will develop serious complications, including liver cirrhosis, end-stage liver disease and hepatocellular carcinoma. Although genotype 1 HCV is currently the most prevalent strain of the virus in Japan, genotype 2 HCV, which now accounts for up to 30% of infections, is rising in prevalence. The current standard of care regimen for the treatment of chronic genotype 2 HCV infection in Japan is 24 weeks of pegylated interferon alpha (Peg-IFNα) and ribavirin (RBV). Although relatively high rates of SVR have been reported in clinical trials with this regimen (71–86%), the use of Peg-IFNα+RBV in an ageing population with progressive liver disease is limited by safety and tolerability issues. Moreover, a substantial number of patients have absolute or relative contraindications to interferon. As a result, many Japanese patients with chronic genotype 2 HCV infection have no available treatment options and are thus at risk for worsening of liver disease and complications of cirrhosis, including hepatocellular carcinoma.
Sofosbuvir (Gilead Sciences) is an oral nucleotide analogue inhibitor of the HCV-specific NS5B polymerase that has recently been approved in the United States and Europe for the treatment of chronic HCV infection. The labelled use for patients with chronic genotype 2 HCV infection is sofosbuvir and RBV for 12 weeks. In phase 3 studies, 12 weeks of treatment with sofosbuvir plus RBV in patients infected with genotype 2 HCV resulted in rates of SVR12 of 97% in treatment-naïve patients, 93% in patients ineligible to receive interferon and 86–90% in previously treated patients.
We conducted a phase 3 trial to determine the efficacy and safety of 12 weeks of sofosbuvir and RBV in treatment-naïve and previously treated Japanese patients with chronic genotype 2 HCV infection with and without compensated cirrhosis.