Sofosbuvir for the treatment of hepatitis C virus

The current treatment for hepatitis C virus (HCV) genotype 1 chronic infection is the addition of direct-acting antivirals (DAAs) with a protease inhibitor (telaprevir or boceprevir) to the pegylated interferon (PEG-IFN) and ribavirin (RBV) regimen. In 2014, sofosbuvir, simeprevir and faldaprevir may be available, each in combination with PEG-IFN/RBV triple therapy. All the HCV enzymes are essential for HCV replication, and are potential drug discovery targets. Therefore, DAAs with different viral targets, including NS3 protease inhibitors, nucleoside/nucleotide analogue and nonnucleoside inhibitors of the RNA-dependent RNA polymerase, and NS5A replication complex inhibitors are under development.

Interestingly, several IFN-free Phase III trials are ongoing with promising results. Among DAAs, sofosbuvir is a potent HCV-specific nucleotide analog (chain terminator). The aim of this article is to review sofosbuvir data, in particular Phase III trials.

Sofosbuvir has a high barrier to resistance with no virologic breakthrough to date. It has a pan-genotypic activity (even though lower rates of response for genotype 3). So far, no safety signal in preclinical/clinical studies has been observed with this compound. It is given orally, once daily, without food effect. Sofosbuvir will first be available in association with PEG-IFN/RBV. Sofosbuvir appears to be a key compound and a backbone for future IFN free treatment regimen.