Interim data for Merck’s VICTRELIS™ (boceprevir) in prior null responder patients with Chronic Hepatitis C genotype 1 to be presented

Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results of an interim analysis from the PROVIDE study, an open-label study examining the efficacy of VICTRELIS™ (boceprevir), the company’s first-in-class, oral hepatitis C virus (HCV) NS3/4A protease inhibitor, in combination with peginterferon alfa and ribavirin (P/R) in adult patients with chronic HCV genotype 1 who had a null response to prior P/R therapy. These patients are significantly less likely to respond to subsequent treatments. In this interim analysis, 38 percent (16/42) of prior null responders achieved a sustained virologic response (SVR)1 when treated with VICTRELIS in combination with P/R. These results, along with several new data analyses of VICTRELIS and MK-5172, Merck’s investigational medicine for the treatment of chronic HCV, will be presented this week at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco.

“In the interim results of the PROVIDE study, approximately one-third of the patients who had a null response to prior peginterferon alfa and ribavirin therapy and failed treatment were able to achieve a sustained virologic response when retreated with VICTRELIS in combination therapy,” said John M. Vierling, M.D., F.A.C.P, professor of Medicine and Surgery at the Baylor College of Medicine in Houston, Texas, director of Baylor Liver Health and Chief of Hepatology, who presented the PROVIDE data. “Null responders are considered to be among the most difficult patients to treat, and we are encouraged by these data.”

Indications and usage for VICTRELIS

VICTRELIS was approved by the U.S. Food and Drug Administration (FDA) on May 13, 2011 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 PROVIDE Study

The PROVIDE study is an ongoing, open-label, single-arm, multicenter rollover study for patients who participated in the P/R control arms of the Phase II and Phase III studies for VICTRELIS and failed to achieve SVR. Of these, 48 patients from the two pivotal Phase III trials for VICTRELIS (HCV SPRINT-2 and HCV RESPOND-2) met the traditional definition for null response (less than a 2 log HCV-RNA decline at treatment week 12). These patients were retreated with a 4-week lead-in of peginterferon alfa-2b (1.5 mcg/kg/week) and ribavirin (600-1,400 mg/day), followed by the addition of VICTRELIS (800 mg three times a day) for 44 weeks. Three of these patients discontinued treatment during the 4-week P/R lead-in phase prior to receiving VICTRELIS, two patients are currently on treatment and one patient is currently in the follow-up phase. Among patients completing treatment and follow-up, 38 percent (16/42) achieved SVR and 16 percent (3/19) relapsed.

New Phase I data presented on the efficacy and safety of MK-5172

New data from an ongoing, randomized, double-blind, placebo-controlled Phase I trial assessing the safety and antiviral activity of MK-5172, Merck’s investigational, once-daily, second-generation oral HCV NS3/4A protease inhibitor, demonstrated a reduction in viral load (HCV-RNA) levels for patients with chronic HCV genotypes 1 or 3 infection after seven days of monotherapy treatment. In the study, 84 adult male patients (ages 18-65) with chronic HCV genotype 1 or 3 infection who had baseline HCV-RNA levels greater than 105 IU/mL and no clinical evidence of cirrhosis received placebo or MK-5172 at doses of 50-800 mg (genotype 1) or 100-800 mg (genotype 3) once daily. Antiviral activity was assessed at multiple time points before, during and after the dosing period. Mean maximum reductions from baseline HCV-RNA with MK-5172 were 5.4 and 5.22 log10 IU/mL for genotype 1 and genotype 3 patients, respectively. No on-treatment viral rebound was observed.

Mean viral load reductions with seven days of MK-5172 monotherapy in genotype 1 patients were similar among all doses. However, more genotype 1 patients achieved HCV-RNA levels of less than 25 IU/mL (the lower limit of quantification) at higher doses, with a greater proportion of patients with HCV-RNA levels persisting below 25 IU/mL at higher doses. In genotype 1 patients, HCV-RNA levels continued to decline after MK-5172 dosing ended, with mean time to viral load nadir occurring more than two days after the final treatment dose. In genotype 3 patients, suppression of HCV-RNA was reduced at doses of MK-5172 below 400 mg. HCV-RNA levels remained suppressed for several days beyond the treatment period in both genotypes. There were no treatment discontinuations due to adverse experiences or safety laboratory abnormalities. A Phase II study of MK-5172 is currently open for patient enrollment. More information can be found on www.clinicaltrials.gov.

Important safety information about VICTRELIS

All contraindications to peginterferon alfa and ribavirin also apply since VICTRELIS must be administered with peginterferon alfa and ribavirin. Because ribavirin may cause birth defects and fetal death, VICTRELIS in combination with peginterferon alfa and ribavirin is contraindicated in pregnant women and in men whose female partners are pregnant. Avoid pregnancy in female patients and female partners of male patients. Patients must have a negative pregnancy test prior to therapy; have monthly pregnancy tests; and use two or more forms of effective contraception, including intrauterine devices and barrier methods, during treatment and for at least 6 months after treatment has concluded. Systemic hormonal contraceptives may not be as effective in women while taking VICTRELIS and concomitant ribavirin.

VICTRELIS is contraindicated in coadministration with drugs that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events. VICTRELIS also is contraindicated in coadministration with potent CYP3A4/5 inducers where significantly reduced VICTRELIS plasma concentrations may be associated with reduced efficacy. Drugs that are contraindicated with VICTRELIS include: alfuzosin, carbamazepine, phenobarbital, phenytoin, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John’s Wort (hypericum perforatum), lovastatin, simvastatin, drosperinone, Revatio® (sildenafil) or Adcirca® (tadalafil) (when used for the treatment of pulmonary arterial hypertension), pimozide, triazolam, and orally administered midazolam.

Anemia and neutropenia have been reported with peginterferon alfa and ribavirin therapy. The addition of VICTRELIS to peginterferon alfa and ribavirin is associated with an additional decrease in hemoglobin concentrations compared to peginterferon alfa and ribavirin alone and/or may result in worsening of neutropenia associated with peginterferon alfa and ribavirin therapy alone. Dose reduction or discontinuation of peginterferon alfa and/or ribavirin may be required. Dose reduction of VICTRELIS is not recommended. VICTRELIS must not be administered in the absence of peginterferon alfa and ribavirin.

Complete blood counts (with white blood cell differential counts) must be conducted in all patients prior to initiating combination therapy with VICTRELIS. Complete blood counts should be obtained at treatment weeks 4, 8 and 12, and should be monitored closely at other time points, as clinically appropriate.

The most commonly reported adverse reactions (greater than 35 percent) in clinical trials in adult patients receiving the combination of VICTRELIS with peginterferon alfa and ribavirin were fatigue, anemia, nausea, headache and dysgeusia. Of these commonly reported adverse reactions, fatigue, anemia, nausea, and dysgeusia occurred at rates greater than or equal to 5 percent above the rates for peginterferon alfa and ribavirin alone in either clinical study. The incidence of these adverse reactions in previously untreated patients who were treated with combination therapy with VICTRELIS compared with peginterferon and ribavirin alone were: fatigue (58 vs. 59 percent), anemia (50 vs. 30 percent), nausea (46 vs. 42 percent) and dysgeusia (35 vs. 16 percent), respectively. The incidence of these adverse reactions in previous treatment-failure patients who were treated with combination therapy with VICTRELIS compared with peginterferon and ribavirin alone were: fatigue (55 vs. 50 percent), anemia (45 vs. 20 percent), nausea (43 vs. 38 percent) and dysgeusia (44 vs. 11 percent), respectively.

VICTRELIS is a strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5. The potential for drug-drug interactions must be considered prior to and during therapy.

Please see U.S. prescribing information at: http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf.

Merck’s global commitment to advancing hepatitis therapy

Merck is committed to building on its strong legacy in the field of viral hepatitis by continuing to discover, develop and deliver vaccines and medicines to help prevent and treat viral hepatitis. In hepatitis C, company researchers developed the first approved therapy for chronic HCV in 1991 and the first combination therapy in 1998. In addition to ongoing studies with VICTRELIS, extensive research efforts are underway to develop additional innovative oral therapies for viral hepatitis treatment.