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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