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™


April 23, 2013 5:39 am ET

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

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

“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

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

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
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