The U.S. Food and Drug Administration (FDA) has approved Merck’s once-daily fixed-dose combination tablet Zepatier (grazoprevir/elbasvir), with or without ribavirin, to treat those with genotypes 1 and 4 of hepatitis C virus (HCV).

Zepatier (ZEP-ah-teer) includes the NS3/4A protease inhibitor grazoprevir and the NS5A replication complex inhibitor elbasvir.

The FDA had granted a breakthrough therapy designation to Zepatier for the treatment of those with HCV genotype 1 who have end-stage kidney disease and who are on dialysis, and those with HCV genotype 4. This designation is granted to treatments that may offer signficant improvement over currently available therapies.

The recommended treatment lengths for Zepatier are 12 or 16 weeks, depending on hep C genotype, treatment history, and for those with genotype 1a, the presence of NS5A polymorphisms, which are certain genetic differences in their virus. According to Merck, the vast majority of individuals eligible for Zepatier treatment would take it for 12 weeks.

Merck has set the price of 12 weeks of Zepatier at $54,600, which is considerably lower than the prices for other hep C treatments, notably from Gilead Sciences and AbbVie.

Those for whom 12 weeks of Zepatier without ribavirin is recommended include: individuals with genotype 1a who are treatment naive or who have failed treatment with interferon and ribavirin and who do not have NS5A polymorphisms; those with genotype 1b who are treatment naive or who have failed interferon and ribavirin treatment; and treatment-naive individuals with genotype 4. For a full chart of the recommended regimens and treatment lengths, see the Merck press release linked below.

The combination tablet was studied in clinical trials including 1,373 people with genotype 1 or 4 of hep C, including those with and without cirrhosis. Participants were treated for 12 or 16 weeks. HCV cure rates ranged between 94 and 97 percent among the participants with genotype 1, and 97 and 100 percent among those with genotype 4.

Among those taking Zepatier without ribavirin, the most common side effects were fatigue, headache and nausea. The most common side effects among those taking the tablet with ribavirin were anemia and headache.

About 1 percent of the participants in clinical trials of the drug experienced elevations of liver enzymes greater than five times the upper limit of normal. Therefore, the FDA advises that those starting treatment with the tablet should undergo liver enzyme tests before and at intervals throughout treatment.

Zepatier should not be given to those with moderate or severe liver impairment (Child Pugh B or C). It should not be combined with the HIV antiretrovirals Reyataz (atazanavir), Prezista (darunavir), Kaletra (lopinavir), Invirase (saquinavir), Aptivus (tipranavir), or Sustiva (efavirenz). Combination tablets with those medications include Evotaz (atazanavir/cobicistat), Prezcobix (darunavir/cobicistat), and Atripla (efavirenz/tenofovir/emtricitabine).

To read the FDA press release on the approval, click here.

To read the Merck press release on the approval, click here.