Phase 2 Study of Chronic Hepatitis C Treatment By Merck Shows Promise

Phase 2 Study of Chronic Hepatitis C Treatment By Merck Shows Promise

shutterstock_130087487Data from the C-WORTHY study evaluating the efficacy of treatment with Grazoprevir/Elbasvir of Chronic Hepatitis C in genotype 1 infected treatment-naïve and non-responders to peg-interferon/ribavirin (RP) patients was announced by Merck, known as MSD outside the United States and Canada. The C-WORTHy study was presented at the 65th American Association for the Study of Liver Diseases (AASLD) Annual Meeting (also known as The Liver Meeting®) in oral presentations, and published as two papers by Dr. Eric Lawitz of The Texas Liver Institute and Dr. Mark Sulkowski from Johns Hopkins University School of Medicine in The Lancet.

Presently, there is an urgent need for treatment based on an interferon-free, all-oral, short-duration therapy for hepatitis C virus (HCV) that would be effective for various groups of infected patients, such as those with cirrhosis or do not respond to pegylated interferon (peg interferon) plus ribavirin (PR-null responders). In addition, patients with hepatitis C virus (HCV) mono-infected or co-infected with HIV/HCV are in urgent need of safe, effective, all-oral HCV therapies.

The C-WORTHY trial (number NCT01717326) is a randomized, open-label phase 2 trial of grazoprevir plus elbasvir with or without ribavirin in patients with cirrhosis or PR-null responders and in patients without cirrhosis that were mono-infected with HCV or co-infected with HIV/HCV. In this study, the researchers evaluated the efficacy and safety of grazoprevir (MK-5172; HCV NS3/4A protease inhibitor) and two doses of elbasvir (MK-8742; HCV NS5A inhibitor).

The authors randomly distributed the patients mono-infected with HCV to be treated either with grazoprevir (100 mg) plus elbasvir (20 mg or 50 mg) with or without ribavirin for 8 or 12 weeks, while patients co-infected with HIV/HCV would be treated for 12 weeks. For this study, the patients recruited were previously untreated adults aged 18 years or older with chronic HCV genoype 1 infection and HCV RNA at least 10,000 IU/mL in peripheral blood without evidence of cirrhosis, hepatocellular carcinoma, or decompensated liver disease. Moreover, the researchers reported the data of two cohorts of previously untreated patients with cirrhosis (cohort 1) and those with previous PR-null response with or without cirrhosis (cohort 2) enrolled in part B of the study. The patients were randomly distributed to receive grazoprevir (100 mg daily) and elbasvir (50 mg daily) with or without ribavirin during 12 or 18 weeks. The recruited patients were adults with age of 18 years or older with chronic HCV genotype 1 infection and HCV RNA concentrations of 10,000 IU/mL or higher in peripheral blood. The primary endpoint in the various studies was the percentage of patients achieving HCV RNA less than 25 IU/mL at 12 weeks after the end of treatment (SVR12).

“Merck is committed to developing an efficacious, well-tolerated therapy suitable for a broad spectrum of patients with HCV,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories, in the press release. “We are encouraged by the findings for grazoprevir/elbasvir in the C-WORTHy trial and look forward to advancing our broad Phase 3 program, which includes hard-to-cure patients that are of the highest need and least studied to date.”

The researchers found that the treatment of previously untreated patients with cirrhosis and previous PR-null responders with and without cirrhosis with grazoprevir plus elbasvir, both with and without ribavirin, and during 12 and 18 weeks treatment, showed high rates of efficiency. Notably, the patients mono-infected with HCV and previously untreated or co-infected with HIV/HCV without cirrhosis treated with grazoprevir plus elbasvir, once a day, with or without ribavirin during 12 weeks achieved SVR12 rates of 87—98%. The researchers claim that these results support the development of grazoprevir plus elbasvir into phase 3 clinical trial. Finally, in 2015, Merck is planning to submit to the Food and Drug Administration the New Drug Application for grazoprevir/elbasvir.

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