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Interferon-Free Drug Combo MK-5172 and MK-8742 ± Ribavirin

Grazoprevir (MK-5172) with elbasvir (MK8742) ± ribavirin (RBV) was approved by the FDA as a new oral medicine to treat chronic hepatitis C (Hep C). Zepatier, the Merck brand name for this combination drug, was granted approval by the FDA in 2016 for genotypes 1 and 4 after the completion of clinical trials.1

Clinical trial evaluations

Clinical trials tested direct acting agents on the hepatitis C virus (HCV). Patients with different genotypes received an interferon-free fixed dose combination NS3/4A protease inhibitor grazoprevir (MK-5172) and the nonstructural protein (NS5A) inhibitor elbasvir (MK-8742), ± ribavirin (RBV) during these studies.2

Trials were conducted with people who have Hep C who have not received prior drug treatment (treatment-naïve), and do not have cirrhosis of the liver (non-cirrhotic). There were different sub groups of the study with other parameters including having HIV, a previous lack of response to antiviral therapy, or HCV RNA levels ≥10,000 IU/mL.3

Completed trials

C-WORTHy and C-SPIRIT are the names of two studies completed in 2015 that evaluated the efficacy and safety of interferon-free medications. C-WORTHY evaluated grazoprevir (MK-5172) and elbasvir (MK-8742), ± ribavirin (RBV). C-SPIRIT evaluated grazoprevir (MK-5172) and ribavirin (RBV). The initial phase was completed in 2015. Participants in the study were randomly assigned to MK-5172 (100 mg tablet once daily) and either 20 mg or 50 mg of elbasvir MK-8742, with and without ribavirin. The ribavirin dose was determined by the weight of the participant. The primary study design was for 12 weeks, which is now the standard for administration. Other time frames were also studied.2
Trial success was measured by sustained virologic response (SVR) rates 12 weeks after the end of study therapy. This refers to having an undetectable level of HCV when tested. The successful results ranged from 87% to 100% achievement of undetectable HCV, depending on the sub group of the population studies. The medications were generally well tolerated.2

Safety and side effects

Zepatier (the combination of grazoprevir (MK-5172) and elbasvir (MK-8742) ± ribavirin (RBV)) was well tolerated. The most common side effects were fatigue, headache, and nausea. Anemia and headache appeared more frequently in participants who received the combination with ribavirin. The majority of participants in both studies, C-WORTHY and C-SPIRIT, experienced elevated liver enzyme levels at the beginning of their study.1,2 These elevations normalized during treatment. It is important for health care providers to conduct blood tests prior to initiating treatment as well as during treatment to monitor for toxic levels. Zepatier is not recommended for patients with moderate to severe liver impairment.1,2 Additional information on Zepatier is available in the prescribing information.

Written by: Jonathan Simmons | Last reviewed: July 2019.
  1. FDA approves Zepatier for treatment of chronic hepatitis C genotypes 1 and 4. Available at: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm483828.htm. Accessed 3.13.19.
  2. A Study of the Combination Regimen Grazoprevir (MK-5172) and Elbasvir (MK-8742) ± Ribavirin in Participants With Chronic Hepatitis C (MK-5172-035) (C-WORTHy) Available at: https://clinicaltrials.gov/ct2/show/results/NCT01717326?view=results. Accessed 3.12.19.
  3. An Efficacy and Safety Study of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in the Treatment of Chronic Hepatitis C Virus (HCV) Genotype (GT)1, 4, or 6 Infection in Treatment-Naïve Participants Who are on Opiate Substitution Therapy (MK-5172-062). Available at: https://www.merck.com/clinical-trials/study.html?id=5172-062&kw=MK-5172&cond=Chronic+Hepatitis+C. Accessed 3.12.19.