Last updated on April 21, 2014 at 7:52 EDT

Merck Announces Presentation of Interim Data from Study of Investigational Combination of HCV Therapies MK-5172 and MK-8742 at the 2013 American Association for the Study of Liver Diseases (AASLD) Annual Meeting

November 2, 2013

Sustained virologic response at post-treatment follow-up week 12 (SVR
12) seen in 100 per cent of patients to date in two of the three
combination arms studied

MONTREAL, Nov. 2, 2013 /CNW/ – Merck (NYSE: MRK), known as MSD outside
of the United States and Canada, announced interim results from an
ongoing Phase II clinical trial evaluating the efficacy and safety of
an all-oral regimen combining once-daily MK-5172, an investigational
hepatitis C virus (HCV) NS3/4A protease inhibitor, and MK-8742, an
investigational HCV NS5A replication complex inhibitor, with or without
twice-daily ribavirin, administered for 12 weeks to treatment-naïve,
non-cirrhotic patients with genotype 1a and 1b HCV infection, the
C-WORTHY Study. The interim results show that the administration of
MK-5172 and MK-8742 in combination is associated with a sustained
virologic response (lack of detectable and quantifiable HCV virus) 12
weeks following the end of study therapy (SVR12). Merck previously
announced that the U.S. Food and Drug Administration (FDA) granted
Breakthrough Therapy designation to MK-5172/MK-8742 for treatment of
chronic HCV infection.

“Chronic hepatitis C continues to be a major public health issue in
Canada and the positive results from these studies provide new hope to
patients and those who treat the disease,” says Alnoor Ramji, M.D.,
Clinical Assistant Professor at the University of British Columbia and
a study investigator. “With future therapies, such as MK-5172 and
MK-8742, we are on the path to highly effective non-interferon based
regimens to eradicate HCV in a broad range of HCV patients, including
those that are more difficult to treat.”


In the C-WORTHY Study, 65 patients (45 per cent male, 11 per cent
African American, and 58 per cent genotype 1a infection) were enrolled
in one of three 12-week treatment arms (see TABLE). The ribavirin (RBV)
arms were stratified by genotype 1a versus genotype 1b. The RBV-free
arm included only genotype 1b-infected patients. Virologic response was
assessed each week during treatment and at 2, 4, 8, 12 and 24 weeks
after the end of treatment. The primary efficacy endpoint of the trial
was the proportion of patients who achieved sustained virologic
response at post-treatment follow-up week 12 (SVR12).

The primary analysis population was per protocol, including patients who
did not have protocol violations and had received the correct study
medications. A total of 58/65 enrolled patients met these criteria (see

Of the seven patients who were not in the per-protocol population, four
achieved SVR12 and three discontinued early for reasons other than
adverse experiences or virologic failure.

Among the entire study population of 65 patients, one patient (1.5 per
cent) experienced a relapse with detectable HCV RNA at follow-up week 4
and 12.


Primary Analysis Population: Per Protocol*

    |Arm|Regimen                       |N |GT1a / GT1b| SVR4 |   SVR12# |
    |   |MK-5172 (100 mg) + MK-8742 (20|  |           |22/22 |   21/21  |
    | 1 |mg)                           |22| 76% / 24% |(100%)|   (100%) |
    |   |+ ribavirin                   |  |           |      |          |
    |   |MK-5172 (100 mg) + MK-8742 (50|  |           |23/24 |   23/24  |
    | 2 |mg)                           |24| 70% / 30% |(96%) |   (96%)  |
    |   |+ ribavirin                   |  |           |      |          |
    | 3 |MK-5172 (100 mg) + MK-8742 (50|12| 0% / 100% |12/12 |  11/11   |
    |   |mg)                           |  |           |(100%)|(100%)    |
    |* Seven Patients were excluded from the Per Protocol Population    |
    |                                                                   |
    |    --  4 patients received incorrect RBV doses (3 received 50% of |
    |        the prescribed dose:                                       |
    |        1 given RBV in the RBV-free arm); all achieved HCV-RNA 25  |
    |        IU/mL at FU12                                              |
    |    --  3 patients discontinued early:1 patient at Day 3 (violated |
    |        protocol inclusion                                         |
    |        criterion), and 2 patients at Day 22 & Day 35 (withdrew    |
    |        consent - patients had                                     |
    |        undetectable HCV RNA at the time of discontinuation)       |
    |#Two patients have not reached SVR12                               |

The most frequently reported adverse events occurring in the study were
fatigue (26 per cent), headache (22 per cent), nausea (18 per cent),
diarrhea (12 per cent), dizziness (11 per cent) and rash (11 per cent).
The incidence of anemia (10 mg/dL hemoglobin) and elevated total
bilirubin levels to 2 times the upper limit of normal was 19 percent
and 4 per cent, respectively, in the RBV containing arms (combined arms
1 and 2), and 0 per cent and 0 percent, respectively, in the RBV-free
arm. No grade 3 or 4 laboratory abnormalities were observed. There were
eight cases of rash. Seven cases of rash were observed in the
ribavirin-containing arms; half of these cases were attributed to
ribavirin. The single case in the RBV-free arm was not study drug
related and was mild in intensity. No early discontinuations due to
drug-related adverse events were recorded.

The C-WORTHY trial has been expanded to evaluate the safety and efficacy
of MK-5172 and MK-8742, with or without RBV, in difficult-to-cure HCV
genotype 1-infected patient populations. Approximately 400 additional
HCV genotype 1-infected patients have been enrolled in this trial. The
expanded C-WORTHY study is testing:

        --  8 week regimen of MK-5172/MK-8742 + RBV in treatment naïve
            non-cirrhotic patients
        --  12 week regimen of MK-5172/MK-8742 without RBV in
            treatment-naïve non-cirrhotic patients
        --  12 week regimens (MK-5172/MK-8742 with or without RBV) among
            HIV co-infected patients
        --  12 or 18 week regimens (MK-5172/MK-8742 with or without RBV) in
            patients with cirrhosis
        --  12 or 18 week regimens (MK-5172/MK-8742 with or without RBV) in
            patients who had failed to respond to prior peginterferon and
            RBV therapy ("null responders").

Details on the C-WORTHY Study, as well as additional phase II trials for
MK-5172 and MK-8742, can be viewed on ClinicalTrials.gov.

“We are encouraged by these preliminary data for the combination of
MK-5172 and MK-8742,” said Dr. Eliav Barr, vice president infectious
diseases, Merck Research Laboratories. “These data provide further
support that we can advance these candidates, which are currently in
Phase IIB clinical development, into a broader evaluation in a diverse
range of HCV patients.”

Hepatitis C in Canada

Over 300,000 people in Canada are infected with chronic hepatitis C(1) and there are 3,200 to 5,000 newly infected individuals each year.(2) Chronic hepatitis C is a “silent” disease because often no symptoms
appear until your liver is severely damaged. If your body is not able
to fight off the virus, you may develop chronic hepatitis which can
lead to cirrhosis (liver scarring), liver failure and even liver cancer
later in life.(1)

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 about our operations in Canada, visit www.merck.ca.

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

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).


(1) Canadian Liver Foundation. http://www.liver.ca/hepatitis/hepatitis-c.aspx. Accessed October 25, 2013.

(2) Canadian Institutes of Health Research. About the Hep C Research
Initiative. http://www.cihr-irsc.gc.ca/e/38855.html. Accessed October 25, 2013.


Source: PR Newswire