Merck has received a US license for its direct-acting antiviral combination of grazoprevir and elbasvir, to be marketed as Zepatier. The combination of grazoprevir (an HCV protease inhibitor) and elbasvir (an NS5A inhibitor) is dosed once daily for 12 weeks or 16 weeks with or without ribavirin.
The combination has been approved for the treatment of genotypes 1 and 4. Approval is based on results of studies in previously untreated and treatment-experienced patients. It has not been approved for use in people with moderate or severe hepatic impairment (Child Pugh B or C stages).
A 12-week treatment course is recommended for all patients apart from those with genotype 4 who have previous experience of pegylated interferon and ribavirin, or people with genotype 1a and baseline NS5A mutations indicating possible resistance to NS5A inhibitors. These groups of patients should receive a 16-week course of treatment.
Use in combination with ribavirin is recommended for the following groups of people:
- Genotype 1a: previously untreated people and people previously treated with pegylated interferon and ribavirin if they have baseline NS5A mutations indicating possible resistance to NS5A inhibitors
- Genotype 1a and 1b: people previously treated with pegylated interferon, ribavirin and a protease inhibitor (boceprevir, simeprevir or telaprevir)
- Genotype 4: people previously treated with pegylated interferon and ribavirin.
Testing for NS5A resistance-associated polymorphisms (positions 28, 30, 31 or 93) is recommended for GT1a-infected patients prior to starting treatment.
Merck has priced its regimen at a list price of $54,600, significantly below the list price established for its chief competitor product, Gilead’s Harvoni (sofosbuvir/ledipasvir). Merck’s price compares with a list price of $94,500 for Harvoni in the United States, although Gilead is believed to have agreed discounts of up to 30% with many insurers.
The European Medicines Agency is reviewing a licensing application for the combination and a decision is expected in 2016.