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11/4/2013 7:03:29 AM

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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

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."

C-WORTHY Study
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 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 per cent) experienced a relapse with detectable HCV RNA at follow-up week 4 and 12.

TABLE

Primary Analysis Population: Per Protocol*

ArmRegimenNGT1a / GT1bSVR4SVR12#
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 & 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 C1 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 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).

___________________________
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 Merck



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