The primary goal of hepatitis C virus (HCV) treatment is to completely eliminate the virus from the patient’s body and thereby reduce or halt the progression of liver fibrosis, preventing further complications, such as cirrhosis and hepatocellular carcinoma. Historically, the standard of care for chronic HCV infections was a lengthy 24- to 48-week course of pegylated interferon (IFN)-alpha (Roche’s Pegasys or Merck’s PegIntron) plus ribavirin (Roche’s Copegus; Merck’s Rebetol; generics). Although effective for some patients, IFN-based treatment options are suboptimal, with overall sustained virologic response (SVR) rates of 45-75% (depending on patient characteristics and viral subtype), significant toxicities (depression, immunological reactions, anemia, and other cytopenias), and a lengthy 24- to 48-week treatment duration. The introduction in 2011 of the first two HCV-specific protease inhibitors, Vertex’s Incivek (telaprevir) and Merck/Roche’s Victrelis (boceprevir), led to improved efficacy outcomes for patients with genotype-1 infections, but treatment entails considerable additional toxicities as well as drastically increased complexity and costs, which constrain uptake of these agents. Treatments for HCV were revolutionized again with the December 2013 approval of Gilead’s Sovaldi (sofosbuvir), the first HCV-specific nucleotide polymerase inhibitor, and Janssen/Medivir’s Olysio (simeprevir), an improved protease inhibitor. The launch of these agents ushered in a new, IFN-free era in treatment of HCV and has driven a dramatic increase in HCV treatment rates.
With the approval of Gilead’s Harvoni, a fixed-dose combination of sofosbuvir and the NS5A inhibitor ledipasvir, in October 2014, the HCV field is once again poised to undergo a radical shift in treatment practice as a wave of new treatment options dispense with both interferon and ribavirin, reduce treatment durations to 8 weeks or less for some patients, and allow for treatment of high unmet need patient populations who previously had little or no hope of achieving SVR. However, these new treatment options are expected to be very costly, raising the critical question of how manage care organization medical and pharmacy directors (MCO MDs and PDs) will manage formulary placement, reimbursement policy, and cost controls in the new world of interferon-free therapy for all.