Rationale: The nonstructural proteins (NS) 3, 4A, and 5A (NS3, NS4A, and NS5A) are key enzymes in hepatitis C virus (HCV) RNA replication. Drugs targeting these enzymes are expected to inhibit HCV replication, thus lowering viral loads.
Technology Description: Zepatier (grazoprevir, 100 milligrams [mg] and elbasvir, 50 mg; Merck Sharp & Dohme Corp.) is a “next-generation” direct-acting antiviral (DAA) administered as a once-daily tablet for the treatment of HCV genotype 1 or 4 infections. Elbasvir is an HCV NS5A inhibitor that is active in all HCV genotypes and has been developed for combination use with grazoprevir, an NS3/4A protease inhibitor for multiple genotypes. This treatment may be administered with or without twice-daily, weight-based ribavirin.
Controversy: Zepatier is a recently approved drug for HCV genotype 1 or 4 infections, but more recently Food and Drug Administration–approved drugs, which target a broader spectrum of HCV genotypes (Epclusa and Harvoni; Gilead Sciences Inc.), will also compete with Zepatier for market share. The list price of Zepatier is currently the lowest of the interferon-free DAA regimens recommended for HCV genotype 1 or 4 infections, with demonstrated efficacy in many special populations; therefore, assessment of safety and efficacy and comparative safety and efficacy is warranted.
Key Questions:
Does Zepatier result in high rates of sustained virologic response (SVR) and low rates of treatment failure (i.e., virologic relapse)?
How does Zepatier compare with other treatments for hepatitis C virus (HCV) for increasing SVR rates and reducing treatment failure (i.e., virologic relapse) rates?
What harms and complications are associated with Zepatier?
Have definitive patient selection criteria been established for Zepatier for the treatment of chronic HCV infections?
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