Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the presentation of the latest interim data from a Phase II, multi-center, randomized, dose-ranging clinical trial evaluating the safety and antiviral activity of MK-5172, for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection. MK-5172 is an investigational, once-daily, oral HCV NS3/4A protease inhibitor that in preclinical evaluations has demonstrated a high barrier to resistance. These data will be presented at the International Liver Congress™ during the 48th meeting of the European Association for the Study of the Liver being held in Amsterdam on Friday, April 26, from 4-6 p.m. local time. Earlier interim data from this study was previously presented at the American Association for the Study of Liver Diseases Annual Meeting in November 2012.
“We continue to build upon our clinical experience of MK-5172 in chronic hepatitis C”
MK-5172 in combination with peginterferon alfa-2b and ribavirin (PR) was evaluated versus VICTRELIS® (boceprevir), 200 mg Capsules, in combination with PR in treatment-naïve, non-cirrhotic patients with HCV genotype 1. A total of 332 patients were enrolled and randomized 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 U.S. product circular.
For those patients evaluated to date, the rates of sustained viral response (SVR) at week 24 follow-up (SVR24) were 86 percent (55/64) and 92 percent (61/66) for the MK-5172 100 mg plus PR and MK-5172 200 mg plus PR arms, respectively, versus 54 percent (31/57) in the boceprevir plus PR active control arm. 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 combining such patients with those who were evaluable for the SVR24 endpoint showed that undetectable HCV RNA, (HCV RNA negative), at last visit on record was achieved for 92 percent (61/66), 99 percent (67/68), and 67 percent (44/66) for MK-5172 100 mg plus PR, MK-5172 200 mg plus PR, and boceprevir plus PR groups respectively.
"We continue to build upon our clinical experience of MK-5172 in chronic hepatitis C," said Eliav Barr, M.D., vice president, Infectious Diseases, Project Leadership and Management, Merck Research Laboratories. "The interim findings from this study provide clear direction for future larger trials designed to evaluate MK-5172 in novel all oral regimens for HCV."
Following a review of safety data, an increased incidence of elevated liver transaminases (ALT/AST), a marker of liver toxicity, was observed in patients receiving the highest doses (400 mg and 800 mg) of MK-5172 and consequently the dose of MK-5172 was reduced to 100 mg in these patients. In the patients administered higher doses of 400 mg and 800 mg MK-5172, 91 percent (58/64) and 87 percent (52/60) of patients respectively achieved SVR24.
Of the patients evaluated so far in this study, the incidence of bilirubin increase and/or a late transaminase increase in the 100 mg dose of MK-5172 was comparable to control. In 124 patients receiving a higher dose of MK-5172 (67 on 400 mg and 65 on 800 mg), transaminase levels normalized by week 4 on therapy but increased to more than twice the upper limit of normal thereafter; in the majority of these patients levels declined with continued MK-5172 treatment at the 100 mg level and normalized by week 16. Overall, rates of serious adverse events were 9 percent (25/266) and 8 percent (5/66) for MK-5172 plus PR arms and control group respectively. The incidence of rash was 20 percent (54 /266) and 27 percent (18/66) for MK-5172 plus PR arms and control group respectively. Rates of anemia in MK-5172 plus PR arms, 18 percent (48/266), were lower than those observed in the control group, 27 percent (18/66).
In a separate poster, (#403), Merck scientists presented data from the analysis of blood samples from patients in this Phase II study evaluating MK-5172 plus PR. They evaluated the relationship between MK-5172 plasma levels and elevated liver transaminase activity. A dose dependent, non-linear relationship was determined between exposure to high levels of MK-5172 and the probability of liver toxicity. Based on this data and the SVR data with MK-5172, the 100 mg dose level is being evaluated in trials of interferon-containing and interferon-free regimens.