Merck Reports Phase III Study Results Evaluating Anemia Management Strategies Used With VICTRELIS® (boceprevir) Combination Therapy

Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced final results from a Phase III, open-label study designed to compare the impact of two anemia management strategies on sustained virologic response (SVR) ¹ in patients with chronic hepatitis C virus (HCV) genotype 1 infection treated with VICTRELIS ^® (boceprevir) in combination with PEGINTRON ^® (peginterferon alfa-2b) and ribavirin (P/R). The rates of SVR were 71 percent for both groups: those patients whose anemia was managed by ribavirin dose reduction (178/249) and those patients whose anemia was managed by the addition of erythropoietin (EPO) (178/251). The rates of relapse were identical at 10 percent in both groups. These results were presented today for the first time as part of a late breaker poster session [poster #1419] at The International Liver Congress™ / 47th European Association for the Study of the Liver (EASL) annual meeting.

"Chronic hepatitis C treatment regimens with peginterferon alfa and ribavirin are commonly associated with the development of anemia, and this effect is further increased with the addition of VICTRELIS,” said Fred Poordad, M.D., chief of hepatology and liver transplantation, Cedars-Sinai Medical Center, Los Angeles. "The results of this study show there was no difference in SVR rates among these anemia management strategies and that ribavirin dose reduction should be the primary strategy for managing anemia in patients taking VICTRELIS combination therapy.”

Indications and usage for VICTRELIS

VICTRELIS is indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 (G1) infection, in combination with peginterferon alfa and ribavirin (P/R), in adult patients (18 years and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy.

The following points should be considered when initiating VICTRELIS for treatment of chronic HCV infection:

• VICTRELIS must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin.
• VICTRELIS efficacy has not been studied in patients who have previously failed therapy with a treatment regimen that includes VICTRELIS or other HCV NS3/4A protease inhibitors.
• VICTRELIS in combination with peginterferon alfa and ribavirin has not been studied in patients documented to be historical null responders (less than a 2 log HCV-RNA decline by treatment week 12) during prior therapy with peginterferon alfa and ribavirin. The clinical studies included patients who were poorly interferon responsive. Patients with less than 0.5 log HCV-RNA decline in viral load at treatment week 4 with peginterferon alfa plus ribavirin alone are predicted to have a null response (less than a 2 log viral load decline by treatment week 12) to peginterferon alfa and ribavirin therapy.
• Poorly interferon responsive patients who were treated with VICTRELIS in combination with peginterferon alfa and ribavirin have a lower likelihood of achieving a sustained virologic response (SVR), and a higher rate of detection of resistance-associated substitutions upon treatment failure, compared to patients with a greater response to peginterferon alfa and ribavirin.

About the Study

In this study, 687 treatment-naïve adult patients with chronic HCV genotype 1 who had baseline hemoglobin levels of less than or equal to 15 g/dL were enrolled in a multinational, open-label trial and monitored for the development of anemia. Patients were treated with a 4-week lead-in of peginterferon alfa-2b (1.5 mcg/kg/week) and an investigational dose of ribavirin (600-1,400 mg/day), followed by the addition of VICTRELIS (800 mg three times a day) after week 4 for 24 or 44 weeks based on HCV-RNA levels at treatment week 8. Sixteen (16) percent (111/687) of patients were enrolled in Cohort 1 and assigned a fixed-dose regimen that included the 4-week lead-in of P/R followed by the addition of VICTRELIS for 44 weeks. A protocol amendment was then added to allow the use of the response-guided therapy (RGT) paradigm, consistent with findings in the pivotal clinical studies for VICTRELIS, and the rest of the patients were enrolled in Cohort 2. The results for patients receiving the fixed-dose regimen (Cohort 1) versus the RGT paradigm (Cohort 2) did not differ and have been combined in the presentation of these data. Patients with a less than 2-log ₁₀ decline in HCV-RNA at week 12, or a greater than or equal to lower limit of quantification of HCV-RNA at week 24 were considered treatment failures and were discontinued from the studies.

A total of 500 patients developed anemia, defined by having hemoglobin of less than or equal to 10 g/dL (or less than 11 g/dL and were expected to reach less than or equal to 10 g/dL before the next visit). These patients were randomized to receive either ribavirin dose reduction (by 200 to 400 mg/d) or the addition of EPO (40,000 IU/week). A secondary method of anemia management, such as the addition of EPO, ribavirin dose reduction or transfusion, was later permitted if a patient's hemoglobin reached less than or equal to 8.5 g/dL. Treatment was discontinued if hemoglobin levels reached less than or equal to 7.5 g/dL. If the initial hemoglobin measurement qualifying a patient as anemic was less than or equal to 8.5 g/dL, that patient was not randomized to one of the anemia management strategies.

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