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Merck & Co., Inc. (MRK) to Present Updated Interim Data From Phase II Trial Evaluating Investigational NS3/4A Protease Inhibitor MK-5172 for Chronic Hepatitis C Virus Genotype 1 Infection at the International Liver Congress™


4/23/2013 12:22:19 PM

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WHITEHOUSE STATION, N.J., April 23, 2013 – 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 (EASL) being held in Amsterdam on Friday, April 26, from 4:00 – 6:00 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.

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.

About MK-5172

MK-5172 is an investigational orally available HCV NS3/4A protease inhibitor currently being evaluated in combination with other approved and investigational medications in Phase II clinical trials. This includes an all oral combination with MK-8742, Merck’s investigational orally available HCV NS5A inhibitor.

Indications and Usage for VICTRELIS

VICTRELIS® (boceprevir) is indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 (G1) infection, in combination with peginterferon alfa and ribavirin (PR), 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, including prior null responders, partial responders, and relapsers.

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 PR.

• The efficacy of VICTRELIS 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.

• Poorly interferon responsive patients who were treated with VICTRELIS in combination with PR 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 PR.

Important Safety Information about VICTRELIS

All contraindications to PR also apply since VICTRELIS must be administered with PR. Because ribavirin may cause birth defects and fetal death, VICTRELIS in combination with PR 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 2 or more forms of effective contraception during treatment and for at least 6 months after treatment has concluded. One of these forms of contraception can be a combined oral contraceptive product containing at least 1 mg of norethindrone. Oral contraceptives containing lower doses of norethindrone and other forms of hormonal contraception have not been studied or are contraindicated.

VICTRELIS is contraindicated in patients with a history of a hypersensitivity reaction to VICTRELIS. 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 is also 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, drospirenone, Revatio® (sildenafil) or Adcirca® (tadalafil) (when used for the treatment of pulmonary arterial hypertension), pimozide, triazolam, and orally administered midazolam.

Anemia and/or Neutropenia – The addition of VICTRELIS to PR is associated with an additional decrease in hemoglobin concentrations compared with PR alone and/or may result in worsening of neutropenia associated with PR therapy alone. Dose reduction or discontinuation of peginterferon alfa and/or ribavirin may be required. If peginterferon alfa or ribavirin is permanently discontinued, VICTRELIS must also be discontinued. Dose reduction of VICTRELIS is not recommended. VICTRELIS must not be administered in the absence of PR.

Complete blood count (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 2, 4, 8, and 12, and should be monitored closely at other time points, as clinically appropriate. Serious acute hypersensitivity reactions (eg, urticaria, angioedema) have been observed during combination therapy with VICTRELIS and PR. If such an acute reaction occurs, combination therapy should be discontinued and appropriate medical therapy immediately instituted.

The most commonly reported adverse reactions (>35%) in clinical trials in adult patients receiving the combination of VICTRELIS with PR were: fatigue, anemia, nausea, headache, and dysgeusia. Of these commonly reported adverse reactions, fatigue, anemia, nausea, and dysgeusia occurred at rates =5% above the rates for PR alone in either clinical study. The incidence of these adverse reactions in previously untreated subjects that were treated with combination therapy with VICTRELIS compared with PR alone were: fatigue (58% vs 59%), anemia (50% vs 30%), nausea (46% vs 42%), and dysgeusia (35% vs 16%), respectively. The incidence of these adverse reactions in previous treatment failure patients that were treated with combination therapy with VICTRELIS compared with PR alone were: fatigue (55% vs 50%), anemia (45% vs 20%), nausea (43% vs 38%), and dysgeusia (44% vs 11%), 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 Development of Hepatitis Therapies

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 for our marketed and investigational medicines for the treatment of chronic HCV, extensive research efforts are underway to develop additional oral therapies for viral hepatitis treatment.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside of the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

Merck forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2012 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).



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