Fixed-dose combination of sofosbuvir and ledipasvir for the treatment of chronic hepatitis C genotype 1.

INTRODUCTION: The recent October 2014 approval of the fixed dose combination (FDC) of the NS5B polymerase inhibitor sofosbuvir (SOF) and the NS5A inhibitor ledipasvir (LDV) for the treatment of treatment-naive and -experienced HCV genotype 1a/1b (HCV-1) has marked a new era of IFN and ribavirin free treatment for chronic hepatitis C. SOF/LDV combination is approved for 12 weeks in treatment-naive patients with and without cirrhosis. For treatment-experienced patients, it is approved for 12 weeks in patients without cirrhosis but for 24 weeks in patients with cirrhosis. A shorter 8-week course of treatment can be considered for treatment-naive patients who have pretreatment HCV RNA of < 6 million IU/ml and do not have cirrhosis. AREAS COVERED: The purpose of this synopsis is to review the pharmacotherapy and results of pivotal clinical trials for SOF/LDV as the current standard-of-care for HCV-1 patients. We also briefly discuss emerging data with SOF/LDV for certain special populations. Preliminary data is also emerging for HCV genotypes non-1, but their discussion is beyond the scope of this synopsis. The review was done based on data from Phase I, II and III published studies as well as data presented at major national and international meetings. EXPERT OPINION: The FDC of LDV (90 mg) and SOF (400 mg) has a sustained virologic response of approximately 96% when given as a once-a-day pill for 3 months to both treatment-naive and -experienced HCV-1 patients with the exception of prior null responders with cirrhosis. The latter group of patients also achieves high sustained virologic response of 95% but with therapy for 24 weeks. In addition, emerging data suggest that this FDC regimen may be effective in the treatment of HCV-1 co-infected patients with HIV, HCV-1 and -4, patients with cirrhosis and hepatic decompensation and those with post-liver transplant HCV recurrence.