Merck’s Pivotal Phase 3 C-EDGE Program Evaluating Grazoprevir/Elbasvir Shows High Sustained Virologic Responses Across Broad Range of Patients with Chronic Hepatitis C Virus Infection

Data Sets Include Treatment-Naïve, Treatment-Experienced and HIV Co-Infected Patients with Chronic Hepatitis C Virus Genotypes 1, 4 or 6 Infection

Merck Remains on Track to Submit New Drug Application (NDA) to U.S. Food and Drug Administration (FDA) in First Half of 2015

Friday, April 24, 2015 1:00 am EDT

VIENNA--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the first presentations of data from the company’s ongoing C-EDGE pivotal Phase 3 clinical trial program evaluating the investigational once-daily tablet grazoprevir/elbasvir (100mg/50mg) in patients with or without cirrhosis who are infected with chronic hepatitis C virus (HCV) genotypes 1, 4 or 6 (GT1, 4 or 6).¹ Patients in both the HCV infected, treatment-naïve (C-EDGE TN), and HIV/HCV co-infected, treatment-naïve (C-EDGE CO-INFXN) trials treated for 12 weeks achieved rates of sustained virologic response 12 weeks after the completion of treatment (SVR12) of 95 percent (299/316 and 207/218, respectively). In addition, HCV infected, treatment-experienced patients (C-EDGE TE) treated with or without ribavirin (RBV) for 12 weeks achieved SVR12 rates of 94 percent (98/104) and 92 percent (97/105), respectively, and those treated for 16 weeks achieved SVR12 rates of 97 percent (103/106) and 92 percent (97/105), respectively. These data were presented at The International Liver Congress^TM 2015 – the 50^th annual congress of the European Association for the Study of the Liver (Abstract #G07, E-Poster P0886 and E-Poster P0887). A paper detailing the findings of C-EDGE TN was published online in the Annals of Internal Medicine today.

“Patients with co-morbidities and varying treatment experiences represent important segments of the chronic hepatitis C population in need of additional innovative treatment options,” said Dr. Eric Lawitz, vice president, scientific and research development, The Texas Liver Institute and clinical professor of medicine, The University of Texas Health Science Center, San Antonio. “These findings are important because they demonstrate that a single pill of grazoprevir/elbasvir taken once-daily achieved consistently high rates of SVR12 in the patient populations studied.”

“At Merck, we continue to build upon our clinical experience using grazoprevir/elbasvir across diverse populations of patients infected with chronic hepatitis C virus,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “We remain on track to submit a New Drug Application with the U.S. Food and Drug Administration in the first half of 2015.”

C-EDGE TN Overview and Additional Findings

C-EDGE TN is a randomized, blinded, placebo-controlled trial evaluating the efficacy and safety of grazoprevir/elbasvir in treatment-naïve patients with or without cirrhosis infected with chronic HCV GT1, 4 or 6 who received therapy for 12 weeks. Patients were randomized to an immediate treatment group that received grazoprevir/elbasvir for 12 weeks or to a deferred treatment group that received placebo for 12 weeks, were followed for an additional four weeks, and then received open label grazoprevir/elbasvir for the next 12 weeks. The primary efficacy analysis included those patients who received immediate treatment with grazoprevir/elbasvir or placebo. Of the 316 patients who received immediate treatment with grazoprevir/elbasvir, 50 percent were infected with GT1a, 42 percent with GT1b, six percent with GT4 and three percent with GT6. Overall, 22 percent of patients had liver cirrhosis.

In this study, virologic failure occurred in 13 patients (4%) in the immediate treatment group, including one virologic breakthrough and 12 virologic relapses. Serious adverse events occurred in nine (3%) and three (3%) patients in the immediate treatment and corresponding placebo arms, respectively; none were considered drug-related. The most common adverse events reported (greater than 5% incidence) in the immediate treatment and corresponding placebo groups, were headache (17%, 18%), fatigue (16%, 17%), nausea (9%, 8%) and arthralgia (6%, 6%), respectively.

C-EDGE CO-INFXN Overview and Additional Findings

C-EDGE CO-INFXN is an open label, single-arm study evaluating the efficacy and safety of grazoprevir/elbasvir in treatment-naïve patients with or without cirrhosis infected with chronic HCV GT1, 4 or 6 and HIV who received therapy for 12 weeks. Of the 218 patients enrolled in the trial, 66 percent were infected with HCV GT1a, 21 percent with GT1b or other GT1, 13 percent with GT4, and one percent with GT6. Overall, 16 percent of patients had liver cirrhosis.

In this study, virologic failure occurred in seven patients (3%), including six virologic relapses and one reinfection. There were no reported drug-related serious adverse events. The most common (greater than 5% incidence) adverse events reported were fatigue (13%), headache (12%) and nausea (9%).

C-EDGE TE Overview and Additional Findings

C-EDGE TE is a randomized study evaluating the efficacy and safety of once-daily grazoprevir/elbasvir with or without twice-daily RBV in treatment-experienced (prior null response, partial response or relapse with peg-interferon/RBV) patients with or without cirrhosis infected with chronic HCV GT1, 4 or 6 who received therapy for 12 weeks or 16 weeks.

12 week arms

Of the 209 patients randomized to the 12 week arms, 105 patients received grazoprevir/elbasvir only and 104 patients received grazoprevir/elbasvir plus RBV. Patients in the grazoprevir/elbasvir only arm comprised 58 percent GT1a, 33 percent GT1b or other GT1 and nine percent GT4. Overall, 35 percent had liver cirrhosis. Among the 104 patients receiving grazoprevir/elbasvir plus RBV, 58 percent were infected with chronic HCV GT1a, 28 percent GT1b or other GT1, and 14 percent GT4. Overall, 34 percent had liver cirrhosis.

In the grazoprevir/elbasvir only and grazoprevir/elbasvir plus RBV arms, six patients in each arm (6%) were reported to have virologic relapse. No patients were reported to have virologic breakthrough or rebound. Serious adverse events were reported in four patients in the grazoprevir/elbasvir only arm (4%) and three patients in the grazoprevir/elbasvir plus RBV arm (3%). The most common (greater than 10% incidence) adverse events reported in the grazoprevir/elbasvir and grazoprevir/elbasvir plus RBV arms, respectively, were fatigue (19%, 27%), headache (21%, 20%) and nausea (9%, 14%).

16 week arms

Of the 211 patients enrolled in the 16 week arms, 105 patients received grazoprevir/elbasvir only and 106 patients received grazoprevir/elbasvir plus RBV. In the grazoprevir/elbasvir only arm, 46 percent were infected with chronic HCV GT1a, 46 percent with GT1b or other GT1, five percent with GT4 and four percent with GT6. Overall, 36 percent of patients had liver cirrhosis. Among those in the grazoprevir/elbasvir plus RBV arm, 55 percent were infected with chronic HCV GT1a, 36 percent with GT1b or other GT1, eight percent with GT4, and two percent with GT6. Overall, 35 percent had liver cirrhosis.

Among the patients receiving grazoprevir/elbasvir only, three patients (3%) were reported to have virologic breakthrough or rebound and four patients (4%) were reported to have virologic relapse. No virologic failures occurred in patients receiving grazoprevir/elbasvir plus RBV. Serious adverse events were reported in three patients in the grazoprevir/elbasvir only arm (3%) and four patients in the grazoprevir/elbasvir plus RBV arm (4%). The most common (greater than 10% incidence) adverse events reported in the grazoprevir/elbasvir and grazoprevir/elbasvir plus RBV arms, respectively, were fatigue (16%, 30%), headache (19%, 19%) and nausea (4%,17%).

About the C-EDGE Program

C-EDGE is the Phase 3 clinical development program for Merck’s investigational HCV treatment grazoprevir/elbasvir comprising five studies with more than 1,700 patients across more than 25 countries. These studies are evaluating grazoprevir/elbasvir in multiple genotypes (GT1, 4 and 6) and diverse patient populations, including difficult-to-treat patients such as: treatment-experienced, patients with cirrhosis, HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, and those receiving opiate substitution therapies.

Merck’s Commitment to HCV

For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative health care solutions that support people living with HCV worldwide.

About Merck

Today’s Merck is a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies 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 health care through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

Forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. 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 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 except as required by applicable law. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2014 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 Grazoprevir is an HCV NS3/4A protease inhibitor and elbasvir is an HCV NS5A replication complex inhibitor

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Merck Announces Results from Phase 2/3 Study of Investigational Chronic Hepatitis C Therapy Grazoprevir/Elbasvir in Patients with Advanced Chronic Kidney Disease

C-SURFER Trial is First to Investigate an All-Oral Ribavirin-Free Hepatitis C Treatment Regimen in Treatment-Naïve and Treatment-Experienced Patients with Advanced Chronic Kidney Disease Infected with Hepatitis C Virus Genotype 1

Thursday, April 23, 2015 3:30 am EDT

VIENNA--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the first presentation of data from C-SURFER, the company’s Phase 2/3 clinical trial evaluating the investigational once-daily treatment regimen of grazoprevir (100mg) and elbasvir (50mg) in patients with advanced chronic kidney disease (CKD) infected with chronic hepatitis C virus (HCV) genotype 1 (GT1).¹ Treatment-naïve patients and patients who failed prior pegylated interferon HCV therapy, with or without cirrhosis, all of whom had CKD stages 4 or 5, were enrolled.² Following 12 weeks of treatment with grazoprevir and elbasvir, 99 percent (115/116) of patients in the pre-specified primary population for analysis of efficacy data achieved a sustained virologic response 12 weeks after the completion of treatment (SVR12).³ These data will be presented today at The International Liver Congress^TM 2015 – the 50^th annual congress of the European Association for the Study of the Liver (late breaking E-Poster #LP02).

“There is an unmet medical need to treat chronic hepatitis C virus infection in patients with advanced chronic kidney disease,” said Dr. Howard Monsour, Jr., chief of hepatology, Houston Methodist Hospital, Houston, Texas. “In this trial, the first to investigate an all-oral ribavirin-free treatment regimen in treatment-naïve and treatment-experienced CKD patients, treatment with grazoprevir and elbasvir for 12 weeks was effective in this study population with HCV genotype 1 infection.”

The ongoing C-SURFER Phase 2/3 clinical trial is a randomized, parallel-group, placebo-controlled study evaluating patients infected with chronic HCV GT1 with advanced CKD with or without liver cirrhosis. Patients were randomized to one of two study arms:

• Immediate treatment group (ITG), grazoprevir plus elbasvir (blinded) once-daily for 12 weeks (n=111);
• Deferred treatment group (DTG), initially placebo (control arm) for 12 weeks followed by a four week follow-up period and then treatment with grazoprevir plus elbasvir (open label) once-daily for 12 weeks (n=113).

In addition, 11 patients received grazoprevir plus elbasvir (open label) once-daily for 12 weeks with intensive pharmacokinetic sampling.

Of the 122 patients who received grazoprevir plus elbasvir, 83 percent were treatment-naïve, 36 percent had diabetes, 18 percent had stage 4 CKD, 82 percent had stage 5 CKD, 75 percent were receiving hemodialysis and 45 percent were African-American. Among those patients who received at least one dose of grazoprevir plus elbasvir, five percent (6/122) were excluded from the pre-specified primary efficacy analysis population, or modified full analysis set, due to missing data caused by death or early discontinuation for reasons unrelated to study drug. In the modified full analysis set, 99 percent (115/116) of patients receiving grazoprevir plus elbasvir achieved SVR12. One GT1b infected, non-cirrhotic, interferon-intolerant patient showed a viral relapse at follow-up week 12. Within the modified full analysis set, efficacy was consistent across the patient sub-populations assessed. In a supportive analysis of all 122 patients who received at least one dose of grazoprevir plus elbasvir in the ITG arms, including patients who did not complete the study for reasons not related to study drug, 94 percent (115/122) of patients achieved SVR12.

“Merck’s broad clinical development program includes studies dedicated to bringing a once-daily regimen to diverse populations of patients infected with chronic HCV, including certain types of patients with co-morbidities, such as advanced chronic kidney disease,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “These data highlight how emerging innovations in chronic hepatitis C treatment may lead to new options for patient populations in which it historically has been difficult to achieve high rates of sustained viral clearance.”

No patients in the ITG arms discontinued treatment due to adverse events (AEs), while four percent (5/113) of patients in the comparator placebo phase of the DTG arm discontinued treatment due to AEs. The rates of serious AEs reported were 14 percent (16/111) in the ITG arms and 17 percent (19/113) in the placebo control DTG arm. The most common treatment-related AEs in the ITG arms and DTG arm (placebo) were headache (17%, 17%), nausea (15%, 16%) and fatigue (10%, 15%), respectively. There were four deaths reported during the initial treatment phase and the first 14 days of study follow-up. One patient (1%) in the open label arm died from cardiac arrest (not considered related to study medicine) and three patients (2%) in the placebo group died from aortic aneurysm, pneumonia and an unknown cause.

On April 8, 2015, the company announced that the U.S. Food and Drug Administration (FDA) had granted Breakthrough Therapy designation to grazoprevir/elbasvir for the treatment of patients infected with chronic HCV GT1 with end-stage renal disease on hemodialysis and patients infected with chronic HCV GT4. Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

About C-SURFER

C-SURFER is a Phase 2/3 clinical trial evaluating Merck’s investigational grazoprevir plus elbasvir in patients infected with chronic HCV GT1 and with advanced chronic kidney disease (stages 4 and 5, including patients on hemodialysis) with or without liver cirrhosis, which are among those with HCV infection who are most difficult to treat, over 12 weeks.

About Chronic HCV Infection and Chronic Kidney Disease

Chronic HCV infection is both a cause and complication of the treatment of CKD. In patients with CKD, chronic HCV infection is associated with an increased risk of accelerated loss of remaining kidney function, kidney transplant failure and death. Furthermore, patients with chronic HCV infection and advanced CKD represent an unmet need due to a lack of demonstrated HCV treatment options for this group.

About Grazoprevir/Elbasvir

Grazoprevir/elbasvir is an investigational, once-daily single tablet regimen consisting of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A replication complex inhibitor). As part of Merck’s broad clinical trials program, grazoprevir/elbasvir is being studied in multiple HCV genotypes and in patients with difficult-to-treat conditions such as HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, liver cirrhosis and those on opiate substitution therapy.

Merck’s Commitment to HCV

For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative health care solutions that support people living with HCV worldwide.

About Merck

Today’s Merck is a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies 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 health care through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

Forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. 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 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 except as required by applicable law. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2014 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 In Phase 2 studies, grazoprevir/elbasvir are administered as two separate tablets

² Stages 4 and 5 chronic kidney disease are defined as severely or very severely reduced kidney function, based on estimated glomerular filtration rate <30 mL/min/1.73m²

³ Includes patients who received ≥1 dose of study drug and excluded those with missing data because of death or early discontinuation for reasons unrelated to study drug

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Media:
Doris Li, 908-246-5701
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Sarra Herzog, 201-669-6570
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Merck & Co. to submit grazoprevir, elbasvir hepatitis C combination to FDA in 2015

(Ref: Merck & Co., The Lancet, StreetInsider, NASDAQ)

November 11th, 2014
By: Joe Barber

Merck & Co. said Tuesday that it plans to submit a marketing application for its investigational combination regimen of grazoprevir and elbasvir to the FDA in 2015 for the treatment of chronic hepatitis C. The company also reported results from the Phase II C-WORTHy trial, showing that the treatment combination, either with or without ribavirin, was associated with sustained virologic response rates at 12 weeks of 90 percent or greater in both treatment-naïve and -experienced patients. Eliav Barr, vice president of infectious diseases at Merck Research Laboratories, commented "we are encouraged by the findings for grazoprevir/elbasvir in the C-WORTHy trial and look forward to advancing our broad Phase III programme."

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Merck Announces Results from Phase 2 Study of Investigational Chronic Hepatitis C Treatment Grazoprevir/Elbasvir in Genotype 1 Infected Treatment-Naïve and Difficult-to-Cure Patients

Final Results from the C-WORTHy Study (Parts A and B) Presented at The Liver Meeting^® and Published in The Lancet

First Wave of Phase 3 Development Program for Grazoprevir/Elbasvir is Fully Enrolled; Merck Plans to Submit New Drug Application in 2015

Tuesday, November 11, 2014 8:00 am EST

BOSTON--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the presentation of results from a multi-arm Phase 2 clinical trial evaluating grazoprevir/elbasvir (MK-5172/MK-8742, the company’s investigational NS3/4A protease inhibitor and NS5A inhibitor, respectively) with or without ribavirin (RBV) in treatment-naïve and previously-treated (with peg-interferon/ribavirin [PR]) patients with chronic hepatitis C virus (HCV) genotype 1 (GT1) infection -- the C-WORTHy study (Parts A and B). The final results were presented in oral sessions at the 65^th American Association for the Study of Liver Diseases (AASLD) Annual Meeting (also known as The Liver Meeting^®) and published as separate papers online in The Lancet.

“Merck is committed to developing an efficacious, well-tolerated therapy suitable for a broad spectrum of patients with HCV,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “We are encouraged by the findings for grazoprevir/elbasvir in the C-WORTHy trial and look forward to advancing our broad Phase 3 program, which includes hard-to-cure patients that are of the highest need and least studied to date.”

Interim results from the C-WORTHy study were presented in April 2014 at the 49^th Annual Meeting of the European Association for the Study of the Liver (EASL) and announced by Merck.

Results for Treatment-Naïve Cirrhotic Patients and PR Null-Responders

The results for HCV mono-infected treatment-naïve GT1 patients with cirrhosis and GT1 prior null-responders with or without cirrhosis treated with grazoprevir/elbasvir, with or without ribavirin, for 12 weeks or 18 weeks are shown in table 1. The rates of sustained viral response,ⁱ 12 weeks after the completion of therapy (SVR12) were greater than, or equal to, 90 percent regardless of treatment duration or co-administration of RBV.

The rate of virologic failure was five percent (6/123) in treatment-naïve cirrhotic patients and three percent (4/130) in the null-responder population. Treatment was generally well-tolerated. The most common adverse events associated with the administration of grazoprevir/elbasvir in combination with or without RBV were: fatigue (26%), headache (23%) and asthenia (14%). There were no early discontinuations due to adverse events with grazoprevir/elbasvir and no clinically significant abnormalities observed in routinely evaluated biomarkers.

Results for HCV Mono-Infected and HIV/HCV Co-Infected Patients

Treatment-naïve, non-cirrhotic mono-infected GT1 patients and non-cirrhotic HCV GT1 /HIV co-infected patients treated for 12 weeks with grazoprevir/elbasvir with or without RBV, demonstrated high rates of SVR12, as seen in table 2. Among this patient population treated for 12 weeks, the overall rate of virologic failure was four percent (7/188), including three breakthrough failures and four relapses, in both mono- and co-infected patients. In patients treated for eight weeks, the rate of virologic failure was 17 percent (5/30), with five relapses. The most common adverse events with or without RBV were fatigue (23%), headache (20%), nausea (15%) and diarrhea (10%). There were no early discontinuations due to adverse events with grazoprevir/elbasvir and no clinically significant abnormalities observed in routinely evaluated biomarkers.

About the C-WORTHy Study

C-WORTHy is a randomized, dose response, parallel-group, multiple-site, double-blind clinical trial comparing diverse patient populations exposed to different durations of treatment of grazoprevir/elbasvir with or without RBV in patients with chronic HCV infection. In C-WORTHy Parts A and B, a total of 471 patients with chronic HCV GT1 infection with HCV RNA levels of ≥10,000 IU/mL were enrolled and randomized across 16 arms. The patients include hard-to-cure sub-populations, including treatment-naïve patients with liver cirrhosis (12- and 18-week arms, with and without RBV) and prior-null responder patients with and without cirrhosis (12- and 18-week arms, with and without RBV). The lead authors of The Lancet publications and presenters at The Liver Meeting^® are Dr. Eric Lawitz of The Texas Liver Institute and professor of medicine at The University of Texas Health Science Center, San Antonio, TX (C-WORTHy Cirrhotic Patients and Prior Null-Responders); and Dr. Mark Sulkowski, professor of medicine at The Johns Hopkins University School of Medicine, Baltimore, MD (C-WORTHy HCV Mono-Infected and HIV/HCV Co-Infected Patients).

About C-EDGE: Merck’s Phase 3 HCV Program

The results of the C-WORTHy study supported the advancement of grazoprevir/elbasvir into the Phase 3 clinical development program called C-EDGE. The Phase 3 C-EDGE program is evaluating grazoprevir/elbasvir with and without RBV in various genotypes and across a broad range of patient populations with chronic HCV infection, including treatment-naive patients and patients who previously failed PR therapy, patients with and without cirrhosis, patients with chronic kidney disease (including those on hemodialysis), patients with HIV/HCV co-infection, patients on opiate substitution therapy and patients with inherited blood disorders. Merck initiated the first C-EDGE study in April 2014, and the grazoprevir/elbasvir registration studies within the C-EDGE program – including C-EDGE TN (treatment-naïve), C-EDGE CO-INFXN (HIV/HCV co-infected) and C-EDGE TE (treatment-experienced) -- are now fully enrolled. Results from these trials are anticipated in the first half of 2015. Learn more at http://www.merck.com/clinical-trials/.

About Grazoprevir/Elbasvir

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. In October 2013, Merck announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to grazoprevir/elbasvir for treatment of chronic HCV infection. Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. Merck plans to submit the New Drug Application for grazoprevir/elbasvir in 2015.

Merck’s Commitment to HCV

For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative healthcare solutions that support people living with HCV worldwide.

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 prescription medicines, vaccines, biologic therapies 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.

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 healthcare legislation in the United States and internationally; global trends toward healthcare 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 2013 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).

ⁱ Defined as HCV RNA below the limit of quantification or below the limit of detection at the last visit on record – 4, 8, 12, or 24 weeks after the completion of therapy.
ⁱⁱ Virologic failure is the inability to achieve or maintain suppression of viral replication to an HCV RNA level <200 copies/mL.

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Pam Eisele, 267-305-3558
Sarra Herzog, 201-669-6570
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Justin Holko, 908-423-5088

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Interim Data from Proof-of-Concept Study of Merck’s Investigational Hepatitis C Treatment Grazoprevir/Elbasvir in Combination with a Nucleotide Inhibitor (C-SWIFT study) Presented at The Liver Meeting®

Merck Plans to Initiate Phase 2 C-CREST Program to Evaluate Merck’s Triple Combination of Grazoprevir/Elbasvir with MK-3682 (formerly IDX21437), a Novel Nucleotide Inhibitor, in Q1 2015

Sunday, November 9, 2014 6:53 pm EST

BOSTON--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the presentation of interim data from the C-SWIFT study exploring the potential of a candidate triple-therapy regimen consisting of the fixed-dose combination of grazoprevir/elbasvir (MK-5172/MK-8742, MK-5172A), the company’s investigational NS3/4A protease inhibitor and NS5A inhibitor, in combination with sofosbuvir, a nucleotide (NS5B) inhibitor for the treatment of chronic hepatitis C virus (HCV) infection. Preliminary findings in treatment-naïve HCV genotype 1- (GT1) infected non-cirrhotic patients, following six and four weeks of treatment, and patients with cirrhotic disease, following eight and six weeks of treatment, will be presented by Dr. Eric Lawitz, vice president, scientific and research development, The Texas Liver Institute, San Antonio, TX and C-SWIFT lead investigator. This poster presentation is part of a late-breaking abstract session at the 65^th American Association for the Study of Liver Diseases (AASLD) Annual Meeting, also known as The Liver Meeting^®.

“These interim data provide a compelling proof-of-concept for the potential of an eight- or six-week triple therapy course in treatment-naive patients with genotype 1 disease, including cirrhotic patients,” said Dr. Lawitz. “These findings will inform the design of larger studies aimed at understanding the potential of short-duration triple therapy across multiple patient types.”

To date, the investigational triple therapy has shown response rates (sustained virologic response¹ [SVR] at 4/8 weeks following therapy) ranging from 80 percent to 94.7 percent in cirrhotic and non-cirrhotic patients following six and eight weeks of treatment in this study, as shown in table 1. The four-week regimen resulted in sub-optimal efficacy.

All 28 patients not achieving SVR4/8 relapsed following the end of therapy. Of these patients, 25 (89%) were genotype 1a (GT1a) and three (11%) were genotype 1b (GT1b) [82% of enrolled subjects were infected with HCV GT1a at baseline]. Sequence analysis of virologic failures is so far available for 23 patients. Wild type virus was determined to be the cause in 12 of the relapsed patients. In the other relapsed patients, 10 had elbasvir-resistant viral variants and one had a variant resistant to both grazoprevir and elbasvir.

In this study, the co-administration of grazoprevir/elbasvir and sofosbuvir was generally well-tolerated. The most common adverse events associated with the triple regimen were: headache (4%), fatigue (2%) and nausea (2%). One patient withdrew from the study for reasons unrelated to treatment.

“Our goal is to establish a simple, effective, well-tolerated regimen that is applicable across the diverse population of patients with HCV,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “The preliminary data provide us with the confidence to initiate our C-CREST study to evaluate a triple combination comprising Merck’s investigational candidates from three major therapeutic classes of HCV medicines.”

About C-SWIFT

The C-SWIFT study enrolled a total of 102 treatment-naïve patients with HCV genotype 1 (GT1a and GT1b) infection at The Texas Liver Institute, San Antonio, TX. Treatment-naïve, non-cirrhotic patients were randomized to receive the fixed-dose combination of grazoprevir/ elbasvir (one pill containing 100 mg, 50 mg respectively) plus the nucleotide inhibitor sofosbuvir (400 mg) once daily for eight, six or four weeks. Similarly, treatment-naïve, cirrhotic patients were randomized to receive the investigational combination for either eight or six weeks. The primary endpoint of the study is the percentage of patients achieving sustained virologic response 12 weeks after the completion of therapy (SVR12). An additional analysis of patients with genotype 3 (GT3) HCV enrolled in the C-SWIFT study will be presented at a future scientific congress.

About C-CREST

Based upon the interim findings from C-SWIFT and data from the Phase 1 clinical trial for MK-3682, also presented at The Liver Meeting^®, Merck plans to initiate Phase 2 clinical trials evaluating the efficacy and safety of two short-duration triple therapy regimens: MK-3682 in combination with grazoprevir/elbasvir; and MK-3682 in combination with grazoprevir and Merck’s investigational early-stage NS5A inhibitor MK-8408, in non-cirrhotic HCV patients. Part A of the Phase 2 studies is planned to evaluate eight weeks of therapy among non-cirrhotic HCV-infected patients, and Part B studies may evaluate shorter courses of treatment based on findings from Part A.

MK-3682 (formerly IDX21437) Data Presentation at AASLD Annual Meeting

MK-3682 is an investigational oral prodrug HCV nucleotide analogue NS5B polymerase inhibitor. Phase 1/2a clinical trial results for MK-3682 are scheduled to be presented in a poster session (Abstract #1974) at The Liver Meeting^®. HCV infected subjects (24 GT1 and 20 GT2/3) were randomized to receive placebo or 50, 150 or 300 mg of MK-3682 daily for seven days. Following initial pharmacokinetic and pharmacodynamic analysis, enrollment into the 50 mg and 150 mg treatment groups was discontinued due to a small reduction in viral load. In the 300 mg arms, the mean maximum viral load reductions from baseline for 7-day dosing were 4.6 and 4.1 log10 IU/mL in GT 2 (n=3) and GT 3 subjects (n=7), respectively. In GT1a (n=3) and GT1b subjects (n=5), the mean maximum viral load reductions from baseline for 7-day dosing were 4.8 and 3.9 log10 IU/mL respectively.

To date, no discontinuations due to an adverse event and no drug-related serious adverse events have been reported. Most adverse events were mild or moderate in intensity, with no apparent dose effect. There were no clinically significant abnormalities reported in routine blood and urine biomarker panels and physical examinations. Initial results from this study were previously announced by Idenix Pharmaceuticals in April 2014.

About Grazoprevir/Elbasvir

Grazoprevir/elbasvir (MK-5172/MK-8742, MK-5172A) 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. In October 2013, Merck announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to grazoprevir/elbasvir for treatment of chronic HCV infection. Breakthrough therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

Merck’s Commitment to HCV

For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative healthcare solutions that support people living with HCV worldwide.

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 prescription medicines, vaccines, biologic therapies 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.

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 healthcare legislation in the United States and internationally; global trends toward healthcare 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 2013 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 Defined as HCV RNA below the limit of quantification or below the limit of detection at the last visit on record – 4, 8, or 12 weeks after the completion of therapy.

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