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Interim Phase II Data of Merck's Investigational MK-5172 in Combination Therapy in Chronic Hepatitis C Virus Genotype 1 Infection to be Presented at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting
By: PR Newswire
Nov. 10, 2012 09:01 AM
BOSTON, MA, Nov. 10, 2012 /CNW/ - Merck announced interim results from a Phase II, multi-center, randomized, dose-ranging study (n=332) assessing the safety and antiviral activity of MK-5172, an investigational, once-daily, oral NS3/4A protease inhibitor for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection in combination therapy in treatment-naïve patients. These data will be presented this week at The American Association for the Study of Liver Diseases (AASLD) 2012 Annual Meeting.
The primary efficacy endpoint of the study was to evaluate the complete early viral response (cEVR) of four regimens of MK-5172 in combination with peginterferon alfa-2b and ribavirin (P/R) compared to the control arm in which patients received a 4-week lead-in of P/R followed by the addition of boceprevir (VICTRELISTM). cEVR was assessed by the proportion of patients who achieved undetectable virus (HCV RNA) at week 12 and at week 16 in the control. The MK-5172 regimens had rates of cEVR that ranged from 82.8 to 93 percent, versus the control rate of 74.2 percent.
"These initial results are promising as they show we increased viral eradication rates with MK-5172, said Alnoor Ramji, M.D., Clinical Assistant Professor at the University of British Columbia and a study investigator." At present, we will continue to treat persons with genotype 1 hepatitis C with standard of care triple therapy given the already high eradication rates we can achieve. Future therapies, such as MK-5172, may offer higher eradication rates, be better tolerated and have easier dosing schedules, however, it will be sometime before they will be available in Canada."
In the initial cohort, termed the "Vanguard Cohort," (n=136), 96 percent of patients (25/26) who received a regimen containing 100 mg QD of MK-5172 with P/R achieved sustained virologic response (SVR) 12, defined as having undetectable virus (HCV RNA) 12 weeks after treatment ended, compared to 54 percent of patients (13/24) in the control arm. Currently planned studies evaluating interferon-free regimens with MK-5172 will be dosed at 100 mg QD.
"We are excited by these interim results evaluating MK-5172 in combination therapy," said Eliav Barr, M.D., Vice President of Infectious Disease at Merck Research Laboratories. "Our commitment to chronic hepatitis C remains steadfast. We look forward to continuing our studies of MK-5172, including in interferon-free regimens."
Other data to be presented on MK-5172 at AASLD includes results from a preclinical study evaluating the antiviral activities of MK-5172 in combination with MK-8742, an oral HCV NS5A inhibitor in Phase I development.
Boceprevir in Canada
Hepatitis C in Canada
About the Study
After the primary TW 12 analysis of the MK-5172 arms in the Vanguard cohort, patients receiving the 400 mg and 800 mg doses in the Second Cohort were down-dosed due to elevated liver transaminases and began to receive 100 mg in an open-label fashion between weeks 3 and 12 of MK-5172 therapy.
All patients in both cohorts of the study (termed the Combined Cohort when analyzed together) have reached the primary endpoint of the study, cEVR, or have discontinued early. cEVR values reflect both those patients with both undetectable (TND) and detectable unquantifiable (TD(u)) HCV RNA. In the Second Cohort, 134 of 156 patients randomized into the MK-5172 arms are receiving P/R (n=17) or are in the follow-up phase (n=117) of the study. All patients in the Vanguard Cohort who received MK-5172 are in the follow-up phase of the study or have discontinued early.
Of the patients randomized to the MK-5172 arms, 2.3 percent (6/266) met the protocol-defined criteria for virologic failure: one (1) patient was re-infected with genotype 3 infection; and four patients had no detectable (n=3) or low (n=1) levels of MK-5172 at time of failure and for a period of time prior. The primary efficacy analysis included the full analysis set (FAS) of all randomized patients who received at least one dose of study treatment.
SVR12 Results in the Vanguard Cohort
Of those patients with bilirubin elevation, 92 percent (22/24) occurred within the first seven to 23 days of therapy, and their bilirubin levels decreased from peak levels despite continued dosing.
The frequency and severity of ALT/AST elevations were dose dependent. The frequencies of ALT/AST elevations in the MK-5172 100 mg arm and the control arm after TW4 were comparable at 2 percent each, (1/66) and (1/66), respectively. The frequency of ALT/AST elevations observed in the MK-5172 200 mg, MK-5172 400 mg and MK-5172 800 mg arms after TW 4 were higher. One patient in the MK-5172 800 mg arm experienced a serious adverse event due to elevated ALT and bilirubin levels, which returned to normal after stopping therapy.
Merck recently announced plans to initiate two new clinical trials designed to assess the efficacy and safety of MK-5172 in all-oral, interferon-free combination regimens in non-cirrhotic, treatment-naïve patients with chronic HCV genotype 1 infection. More information is available at http://clinicaltrials.gov using identifiers, NCT01717326 and NCT01716156.
Merck's Global Commitment to Advancing Hepatitis Therapy
The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that all of the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; Merck's ability to accurately predict future market conditions; dependence on the effectiveness of Merck's patents and other protections for innovative products; and the exposure to 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 2011 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).
TM Trademark of Schering Corporation, a subsidiary of Merck & Co., Inc. Used under license.
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