Grazoprevir/elbasvir (MK-5172/MK-8742) is an investigational, oral, once-daily, fixed-dose combination chronic HCV treatment, consisting of grazoprevir, an investigational oral, once-daily HCV NS3/4A protease inhibitor, and elbasvir, an investigational oral, once-daily HCV NS5A replication complex inhibitor.
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EASL-Merck reports mid-stage data for MK-5172 and MK-8742, all-oral hepatitis C regimen
In an interim analysis of treatment-naïve, non-cirrhotic patients administered a 12-week regimen of MK-5172/MK-8742, with and without ribavirin (RBV), a sustained viral response1 (SVR) was observed in 98 percent (42/43) of patients administered MK-5172/MK-8742 alone and 94 percent (75/80) in those administered MK-5172/MK-8742 plus RBV.
EASL - Merck To Present New Data for MK-8742 and MK-5172
WHITEHOUSE STATION, N.J. — Merck (NYSE:MRK), known as MSD outside the United States and Canada, announced today that new Phase 2 data for its two investigational hepatitis C virus (HCV) treatments - MK-5172, an investigational HCV NS3/4A protease inhibitor, and MK-8742, an investigational HCV NS5A replication complex inhibitor – are scheduled to be presented at the 49th Annual Meeting of the European Association for the Study of the Liver (EASL), also known as The International Liver Congress™ 2014. The data are from Merck’s overall Phase 2 clinical program. The meeting will take place in London, United Kingdom, April 9 - 13, 2014.
November AASLD Meeting
AASLD-High cure rates seen with Merck oral hepatitis drugs -study
The results appear to confirm Merck will be competitive in the crowded race to develop interferon-free treatments for hepatitis C, assuming they are repeated in larger studies that include more difficult to treat patient populations, such as those not helped by prior therapy.
The 65-patient, 3-arm study tested MK-5172, a protease inhibitor, combined with MK-8742 from a highly promising new class of drugs called NS5A inhibitors for 12 weeks of treatment.
Based on data available at the time the interim results were released, 55 of 56 patients who completed the therapy were considered to be cured of the virus which is transmitted through infected blood from sources such as infected hypodermic needles or blood transfusions.....
Oct 22 2013
Hepatitis C-Merck MK-5172/MK-8742 all-oral combination Gets Breakthrough Therapy Designation
EASL April 28 2013
EASL- MK-5172 : New Drug Holds Promise in Hepatitis
High Sustained Viral Response of MK-5172 with Pegylated Interferon Alfa-2b
and Ribavirin in HCV Genotype 1 Treatment-Naive Non-Cirrhotic Patients -
EASL: Merck to Present Interim Data on MK-5172 from Phase II Trial
MK-5172 and Daclatasvir-Merck Enters Agreement with Bristol-Myers Squibb to Conduct a Phase II Clinical Trial
The planned initiation of the Phase II clinical trial follows the completion of a Phase I safety evaluation of the investigational combination regimen. Under the agreement, Merck will conduct the Phase II clinical trial. Further clinical development activities beyond the Phase II study are not covered as part of this agreement. Additional details of the collaboration were not disclosed.
MK-5172 (Merck & Co., Inc, Whitehouse Station, NJ) is a novel macrocyclic NS3/4a protease inhibitor under phase II clinical development. The compound demonstrates subnanomolar activity against a broad enzyme panel encompassing
major HCV genotypes, notably variants resistant to earlier protease inhibitors.
R155 is the main overlapping position for resistance and different mutations at this amino acid site within NS3 protease confer resistance to nearly all protease inhibitors in development. However, MK-5172 exhibits potent antiviral activity against variants carrying mutations at position R155.
Thus, based on its preclinical profile, MK-5172 is expected to be broadly active against multiple HCV genotypes, including genotype 3 as well as clinically important resistance variants making it highly suited for incorporation into newer all-oral regimens. MK-5172 was given in doses of 50–800 mg QD (monotherapy) to 48 men with HCV genotype 1 and 30 HCV genotype 3 patients for 7 days .
There were six arms (including a placebo arm). The maximum change in HCV levels was a decrease of −5.37 IU/ml in HCV genotype 1 and −4.41 IU/ml in genotype 3 patients. In the genotype 1 patients, 75% (30 of 40 pts) were below the level of HCVRNA quantification (25 IU/ml). The drug was generally well tolerated. In early-stage studies, MK-5172 in various doses has been shown to work across different genotypes  and can be dosed once a day, which makes it an attractive candidate for future clinical development.....read more...
November 10 2012
R E P E A T -- 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)
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.
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.
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.
Nov 2 2012
Hepatitis C MK-5172:Merck Will Initiate all-oral, interferon-free combination
Merck Will Initiate Interferon-Free Phase II Clinical Trials for MK-5172, an Investigational, Once-Daily, Oral Treatment for Chronic Hepatitis C Virus
Friday, November 2, 2012 2:00 pm EDT
"For more than 30 years, Merck has been leading innovation in viral hepatitis.
The science is advancing rapidly, and we recognize that future HCV treatment
regimens will not include interferon,"
WHITEHOUSE STATION, N.J.--Today,
Merck (NYSE: MRK), known as MSD outside of the United States and Canada,
announced plans to initiate two new clinical trials with MK-5172, its
investigational, once-daily, oral HCV NS3/4A protease inhibitor for the
treatment of chronic hepatitis C (HCV) infection. The trials are 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.
“For more than 30 years, Merck has been leading
innovation in viral hepatitis. The science is advancing rapidly, and we
recognize that future HCV treatment regimens will not include interferon," said
Roger Pomerantz, MD, FACP, senior vice president and Global Franchise Head for
Infectious Diseases, Merck Research Laboratories. "The start of these new
studies is the next step in our efforts to develop novel therapeutic regimens
for the treatment of chronic hepatitis C. We look forward to evaluating the
potential role of MK-5172 and our other earlier pipeline candidates for chronic
HCV as part of our continuing commitment to improving patient care.”
The first clinical trial will evaluate a 12-week regimen containing MK-5172,
MK-8742, an oral NS5A inhibitor in Phase I development, and ribavirin in
non-cirrhotic treatment-naïve patients with HCV genotype 1 infection. The second
clinical trial will evaluate 12- and 24-week regimens of MK-5172 in combination
with ribavirin in non-cirrhotic treatment-naïve patients with HCV genotype 1
infection with an IL-28 CC genotype. More information is available at http://clinicaltrials.gov
using identifiers, NCT01717326 and NCT01716156, respectively.
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'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 for our marketed and investigational medicines for
the treatment of chronic HCV, extensive research efforts are underway to develop
additional innovative oral therapies for viral hepatitis treatment.
Today's Merck is a global healthcare leader working
to help the world be well. Merck is known as MSD outside the United Statesand
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, visit www.merck.com and
connect with us on Twitter, Facebook and YouTube.
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