Treatment Effects and Resistance-Associated Variants of Sofosbuvir Regimen for Japanese Patients with Chronic Hepatitis C Virus Genotypes 1 and 2

Abstract

More than 40,000 people have already been treated in Japan since September 2014 when the first interferon-free all-oral therapy with daclatasvir (DCV), an NS5A inhibitor, and asunaprevir (ASV), an NS3/4A protease inhibitor (PI), was approved for treatment of chronic hepatitis C virus genotype 1. On the other hand, regimens containing the nucleic acid-type NS5B polymerase inhibitor sofosbuvir in combination with a PI, NS5A inhibitor, and/or ribavirin are now becoming standard throughout the world and achieving greater than 95 % sustained virological response (SVR) rates against multiple HCV genotypes. On March 23, 2015, sofosbuvir was approved for treatment of genotype 2 in Japan, priced at 61,700 yen per pill. Furthermore, Harvoni, a combination drug containing sofosbuvir co-formulated with the NS5A inhibitor ledipasvir, was approved in Japan on July 3, 2015, for treatment of genotype 1 with pricing set at 81,171 yen per pill. While the 6,800,000 yen price tag of 12 weeks of Harvoni is higher than that of DCV/ASV therapy, the therapy is more effective, and the one pill per day dosing and 12-week duration provides simpler and shorter therapy. Similarly, sofosbuvir is approved for and effective against both genotypes 1 and 2. This review discusses the mechanism and characteristics of sofosbuvir and summarizes results of phase III clinical trials for genotypes 1 and 2 and reports on the effects of antiviral resistance.