New Merck combination pill Zepatier approved for hepatitis C treatment in the United States

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.

Glossary

pegylated interferon

Pegylated interferon, also known as peginterferon, is a chemically modified form of the standard interferon, sometimes used to treat hepatitis B and C. The difference between interferon and peginterferon is the PEG, which stands for a molecule called polyethylene glycol. The PEG does nothing to fight the virus. But by attaching it to the interferon (which does fight the virus), the interferon will stay in the blood much longer. 

treatment-experienced

A person who has previously taken treatment for a condition. Treatment-experienced people may have taken several different regimens before and may have a strain of HIV that is resistant to multiple drug classes.

hepatic

To do with the liver.

antiviral

A drug that acts against a virus or viruses.

European Medicines Agency (EMA)

Regulatory agency that evaluates medicines for safety and efficacy in Europe, performing a similar role to the Food and Drug Administration (FDA) in the United States. The EMA recommends to the European Commission that a medicine can be marketed in the European Union and European Economic Area.

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.