It is estimated that 2.7 to 3.9 million individuals are living with chronic hepatitis C virus (HCV) infection in the United States.1
Recent reports document an increased mortality related to HCV infection, noting that death from this chronic infection has now surpassed mortality from 60 other notable infectious diseases.2
Until very recently, treatment for chronic HCV consisted of a combination regimen that included subcutaneous injection of pegylated interferon alfa and oral ribavirin that resulted in poor virologic response rates and frequent adverse events (AEs). However, in 2011, two first-generation protease inhibitors, telaprevir and boceprevir, were approved by the US Food and Drug Administration (FDA) for the treatment of chronic HCV.3-7
These agents increased the number of patients who achieved a sustained virologic response (SVR), but they did little to improve tolerability, as they were associated with a significant amount of toxicities and still required co-administration with interferon and ribavirin.
In December 2013, the first direct-acting antiviral (DAA), sofosbuvir, was approved.8
Following the release of several other DAAs, the first pan-genotypic combination tablet, sofosbuvir/velpatasvir (Epclusa) was approved in June 2016.9
This review summarizes the efficacy, safety, contraindications, and relevant drugdrug interactions for sofosbuvir/velpatasvir.
FDA APPROVAL / EFFICACY
The FDA approved sofosbuvir/velpatasvir on June 28, 2016, for the treatment of chronic HCV genotypes 1 through 6.9
The combination of sofosbuvir, a NS5B polymerase inhibitor, and velpatasvir, an NS5A replication complex inhibitor, is administered as one tablet daily (sofosbuvir 400 mg/velpatasvir 100 mg), with or without food for 12 weeks, regardless of genotype, for patients who have no findings of cirrhosis or who have compensated cirrhosis.10
For patients with decompensated cirrhosis, ribavirin therapy should be co-administered for the 12-week treatment duration. Among patients with renal insufficiency (ie, estimated creatinine clearance <30mL/min), sofosbuvir/velpatasvir should not be used due to pharmacokinetic studies demonstrating increased serum levels of sofosbuvir and its metabolite in this population.10,11
Four phase 3 trials were conducted that led to the approval of sofosbuvir/velpatasvir.12-14
The initial study evaluating the effects of sofosbuvir/velpatasvir in both previously treated and treatment-naïve patients infected with HCV genotypes 1, 2, 4, 5, or 6 who had varying stages of hepatic fibrosis was conducted in 2014 (ASTRAL-1).12
The FDA subsequently requested that a separate trial evaluating the use of sofosbuvir/ velpatasvir in HCV genotype 2 (ASTRAL-2) and another in HCV genotype 3 (ASTRAL-3) be conducted, each against an active comparator group.13
A subsequent study, ASTRAL-4, was then conducted to determine the effects of sofosbuvir/velpatasvir in patients with HCV genotype 1-6 and decompensated cirrhosis.