Investigational new agent targets chronic hepatitis C virus genotype 1

Interim data from a phase 2, multicenter, randomized, dose-ranging clinical trial evaluating the safety and antiviral activity of MK-5172 (Merck), for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection, was presented at the 2013 International Liver Congress, 48th annual meeting of the European Association for the Study of the Liver, in Amsterdam.

In the study, MK-5172 in combination with peginterferon alfa-2b and ribavirin (PR) was evaluated versus boceprevir (Victrelis) 200-mg capsules, in combination with PR in treatment-naïve, non-cirrhotic patients with HCV genotype 1.

In the study, a total of 332 patients were enrolled and randomly assigned to receive MK-5172 at 100, 200, 400 or 800 mg in combination with PR or boceprevir with PR. MK-5172 was administered for 12 weeks with PR, followed by an additional 12 or 36 weeks of PR therapy (depending on the HCV RNA levels at treatment week 4). Boceprevir was administered according to the US product circular. Patients who discontinued the study for reasons other than virologic failure and were either in follow-up or did not return for week 24 follow-up were, per protocol, formally counted as ‘failures’ in the SVR24 analysis, regardless of their HCV RNA status at the last visit on record. An analysis was then conducted combining such patients with those who were evaluable for the SVR24.

Of the 332 patients evaluated to date, the rates of sustained viral response (SVR) at week 24 follow-up (SVR24) were 86% (55/64) and 92% (61/66) for the MK-5172 100 mg plus PR and MK-5172 200 mg plus PR arms, respectively, versus 54% (31/57) in the boceprevir plus PR active control arm. Some patients had discontinued the study before reaching the follow-up treatment week 24 visit. Combined evaluation of these patients with those evaluated for SVR-24 shows that undetectable HCV RNA, (HCV RNA negative), at last visit on record was achieved for 92% (61/66), 99% (67/68), and 67% (44/66) for MK-5172 100 mg plus PR, MK-5172 200 mg plus PR, and boceprevir plus PR groups respectively.

“Twenty years ago, many doctors were reluctant to treat HCV because the success rates were so low and the burden to patients was high,” Eliav Barr, MD, vice president, Infectious Diseases, Project Leadership and Management, Merck Research Laboratories told Formulary.  “This scenario is rapidly changing.  There have been unprecedented advancements in the treatment of HCV in the last few years that have significantly improved the SVR rates for patients.  Research efforts are underway to further improve SVR rates through the development of novel products. “

This research also will pave the way for interferon-free therapies that may significantly reduce the burden of treatment for patients and potentially allow physicians to treat patients in a shorter period of time, Dr Barr added.  “The future is very bright for patients with HCV and the physicians who treat them and there will be a time very soon when doctors will be hard pressed to come up with a reason not to treat HCV,” he said. 

Chronic hepatitis C is a viral infection of the liver that affects approximately 130 to 170 million people around the world. If left untreated, HCV infection is a potentially serious disease that can damage the liver over time and lead to cirrhosis, end-stage liver disease, and liver cancer. Genotype 1 (G1) is the most common form of hepatitis C, representing nearly three-quarters of infected individuals, including 40% of people with chronic HCV in North America and 50% in Western Europe.