Merck to Present Updated Interim Data from Phase II Trial Evaluating Investigational NS3/4A Protease Inhibitor MK-5172 for

  Merck 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™

Business Wire

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 48^th 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.

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:

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 and
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Merck forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of
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Reform Act of 1995. These statements are based upon the current beliefs and
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that the products will receive the necessary regulatory approvals or that they
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Risks and uncertainties include but are not limited to, general industry
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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


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