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

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November 2, 2013 9:00 am ET

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

Merck (NYSE: MRK), known as MSD outside of the United States and Canada,
announced the presentation of interim data from the ongoing C-WORTHY
Study, a 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 HCV genotype 1a and 1b infection. The
interim data 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) 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.

“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.”

C-WORTHY Study

In the C-WORTHY Study, 65 patients (45% male, 11% African American, and
58% 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
TABLE).

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%)
experienced a relapse with detectable HCV RNA at follow-up week 4 and 12.

TABLE

Primary Analysis Population: Per Protocol*

Arm Regimen N GT1a / GT1b SVR4 SVR12#
1 MK-5172 (100 mg) + MK-8742 (20 mg) + ribavirin 22 76% / 24% 22/22

(100%)

21/21

(100%)

2 MK-5172 (100 mg) + MK-8742 (50 mg) + ribavirin 24 70% / 30% 23/24

(96%)

23/24

(96%)

3 MK-5172 (100 mg) + MK-8742 (50 mg) 12 0% / 100%

12/12
(100%)

11/11

(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 and 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%), headache (22%), nausea (18%), diarrhea (12%), dizziness
(11%) and rash (11%). 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 percent, respectively, in the RBV-containing arms
(combined arms 1 and 2), and 0 percent 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 RBV-containing arms; half of these cases were attributed
to RBV. 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.

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