Click here to close now.

Welcome!

News Feed Item

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

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
Boceprevir was approved for use in Canada in July 2011 for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alpha and ribavirin, in adult patients (18 years of age and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous therapy.1

Hepatitis C in Canada
An estimated 250,000 individuals in Canada are infected with HCV and there are 3,200 to 5,000 newly infected individuals each year.2 HCV damages the liver and may lead to serious complications, including death, when left untreated.3 It is the leading cause of liver transplants in Canada.4

About the Study
This Phase II, multi-center, double blind, randomized, active-controlled, dose ranging, response-guided therapy (RGT) study is designed to examine the safety and antiviral activity of MK-5172 administered with peginterferon alfa-2b (1.5 µg/kg/week) and an investigational, weight-based dose of ribavirin (600-1,400 mg/day) (P/R) in non-cirrhotic, treatment-naïve, adult patients with chronic HCV genotype 1 infection.  In the study, 332 patients were enrolled in two cohorts: the Vanguard Cohort of 136 patients, followed by a Second Cohort of 196 patients. In both cohorts, patients were randomized to one of four MK-5172 treatment arms (100mg QD, 200 mg QD, 400 mg QD, 800 mg QD). All patients received MK-5172 in combination with P/R for 12 weeks followed by P/R for 12 or 36 weeks, depending on treatment response at treatment week 4. If the patient's virus (HCV RNA) was target not detected (TND; <10 IU/mL) at treatment week (TW) 4, then the patient was able to stop all therapy at TW 24. If the patient's virus was target detected unquantifiable (TD(u); <25 IU/mL) or target detected quantifiable (TD(q)) at TW 4, then the patient stopped all therapy at TW 48.  In the control arm, patients received a 4-week lead-in of P/R followed by the addition of boceprevir, administered as recommended in the prescribing information.

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
In the Vanguard Cohort, higher SVR12 rates were achieved across all MK-5172 arms compared to control (FAS) - 96.2 percent (25/26) in the MK-5172 100 mg arm; 86.7 percent (26/30) in the MK-5172 200 mg arm; 87.0 percent (20/23) in the MK-5172 400 mg arm; and 81.5 percent (22/27) in the MK-5172 800 mg arm; versus 54.2 percent (13/24) in the control arm. All patients achieving SVR12 had undetectable (TND) HCV RNA.

Safety Findings
In the MK-5172 arms of the study, there were two transient liver abnormalities observed - elevations in bilirubin before TW4, associated with normalization of ALT/AST levels, and elevations in liver transaminases (ALT/AST) occurring after TW4.

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.

About MK-5172
MK-5172 is an investigational, once-daily, oral HCV NS3/4A protease inhibitor currently in Phase II development that has demonstrated potent in vitro antiviral activity.  Early data on MK-5172 has shown a broad HCV genotypic activity spectrum and in vitro activity against genotype 1a and 1b viral variants that have been associated with resistance to other HCV protease inhibitors, including those in development.  Given the clinical experience of MK-5172 to date, including its potentially high barrier to resistance and antiviral activity across HCV genotypes, Merck will evaluate MK-5172 in treatment regimens in a broad spectrum of patients with chronic HCV infection.

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
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 with VICTRELISTM, extensive research efforts are underway to develop additional innovative 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 the United States and Canada. Through our medicines, vaccines, biologic therapies, and consumer and animal 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.

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. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company's plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck's management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.

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.

References
___________________
1 VICTRELISTM Product Monograph, July 27, 2011, p. 3.

2 Canadian Institutes of Health Research. About the Hep C Research Initiative. http://www.cihr-irsc.gc.ca/e/38855.html. Accessed October 31, 2012.

3 Public Health Agency of Canada. http://www.phac-aspc.gc.ca/hepc/pubs/multiling-hepc/index-eng.php. Accessed October 31, 2012.

4 Canadian Liver Foundation. http://www.liver.ca/Liver_Disease/. Accessed October 31, 2012.

SOURCE MERCK

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
While DevOps most critically and famously fosters collaboration, communication, and integration through cultural change, culture is more of an output than an input. In order to actively drive cultural evolution, organizations must make substantial organizational and process changes, and adopt new technologies, to encourage a DevOps culture. Moderated by Andi Mann, panelists discussed how to balance these three pillars of DevOps, where to focus attention (and resources), where organizations migh...
Containers have changed the mind of IT in DevOps. They enable developers to work with dev, test, stage and production environments identically. Containers provide the right abstraction for microservices and many cloud platforms have integrated them into deployment pipelines. DevOps and Containers together help companies to achieve their business goals faster and more effectively. In his session at DevOps Summit, Ruslan Synytsky, CEO and Co-founder of Jelastic, reviewed the current landscape of...
The enterprise market will drive IoT device adoption over the next five years. In his session at @ThingsExpo, John Greenough, an analyst at BI Intelligence, division of Business Insider, analyzed how companies will adopt IoT products and the associated cost of adopting those products. John Greenough is the lead analyst covering the Internet of Things for BI Intelligence- Business Insider’s paid research service. Numerous IoT companies have cited his analysis of the IoT. Prior to joining BI In...
"ciqada is a combined platform of hardware modules and server products that lets people take their existing devices or new devices and lets them be accessible over the Internet for their users," noted Geoff Engelstein of ciqada, a division of Mars International, in this SYS-CON.tv interview at @ThingsExpo, held June 9-11, 2015, at the Javits Center in New York City.
SYS-CON Events announced today that Secure Infrastructure & Services will exhibit at SYS-CON's 17th International Cloud Expo®, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. Secure Infrastructure & Services (SIAS) is a managed services provider of cloud computing solutions for the IBM Power Systems market. The company helps mid-market firms built on IBM hardware platforms to deploy new levels of reliable and cost-effective computing and hig...
DevOps Summit, taking place Nov 3-5, 2015, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with 17th Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The widespread success of cloud computing is driving the DevOps revolution in enterprise IT. Now as never before, development teams must communicate and collaborate in a dynamic, 24/7/365 environment. There is no time to wait for long development...
Live Webinar with 451 Research Analyst Peter Christy. Join us on Wednesday July 22, 2015, at 10 am PT / 1 pm ET In a world where users are on the Internet and the applications are in the cloud, how do you maintain your historic SLA with your users? Peter Christy, Research Director, Networks at 451 Research, will discuss this new network paradigm, one in which there is no LAN and no WAN, and discuss what users and network administrators gain and give up when migrating to the agile world of clo...
DevOps is about increasing efficiency, but nothing is more inefficient than building the same application twice. However, this is a routine occurrence with enterprise applications that need both a rich desktop web interface and strong mobile support. With recent technological advances from Isomorphic Software and others, it is now feasible to create a rich desktop and tuned mobile experience with a single codebase, without compromising performance or usability.
Containers are revolutionizing the way we deploy and maintain our infrastructures, but monitoring and troubleshooting in a containerized environment can still be painful and impractical. Understanding even basic resource usage is difficult – let alone tracking network connections or malicious activity. In his session at DevOps Summit, Gianluca Borello, Sr. Software Engineer at Sysdig, will cover the current state of the art for container monitoring and visibility, including pros / cons and liv...
SYS-CON Media announced today that CloudBees, the Jenkins Enterprise company, has launched ad campaigns on SYS-CON's DevOps Journal. CloudBees' campaigns focus on the business value of Continuous Delivery and how it has been recognized as a game changer for IT and is now a top priority for organizations, and the best ways to optimize Jenkins to ensure your continuous integration environment is optimally configured.
The 4th International Internet of @ThingsExpo, co-located with the 17th International Cloud Expo - to be held November 3-5, 2015, at the Santa Clara Convention Center in Santa Clara, CA - announces that its Call for Papers is open. The Internet of Things (IoT) is the biggest idea since the creation of the Worldwide Web more than
SYS-CON Events announced today that ProfitBricks, the provider of painless cloud infrastructure, will exhibit at SYS-CON's 17th International Cloud Expo®, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. ProfitBricks is the IaaS provider that offers a painless cloud experience for all IT users, with no learning curve. ProfitBricks boasts flexible cloud servers and networking, an integrated Data Center Designer tool for visual control over the...
"In the IoT space we are helping customers, mostly enterprises and industry verticals where time-to-value is critical, and we help them with the ability to do faster insights and actions using our platform so they can transform their business operations," explained Venkat Eswara, VP of Marketing at Vitria, in this SYS-CON.tv interview at @ThingsExpo, held June 9-11, 2015, at the Javits Center in New York City.
The most often asked question post-DevOps introduction is: “How do I get started?” There’s plenty of information on why DevOps is valid and important, but many managers still struggle with simple basics for how to initiate a DevOps program in their business. They struggle with issues related to current organizational inertia, the lack of experience on Continuous Integration/Delivery, understanding where DevOps will affect revenue and budget, etc. In their session at DevOps Summit, JP Morgenthal...
"We provide a web application framework for building really sophisticated web applications that run on a browser without any installation need so we get used for biotech, defense, and banking applications," noted Charles Kendrick, CTO and Chief Architect at Isomorphic Software, in this SYS-CON.tv interview at @DevOpsSummit (http://DevOpsSummit.SYS-CON.com), held June 9-11, 2015, at the Javits Center in New York