"Merck NYSEMRK known as MSD outside the United States and Canada today announced that the U.S. Food and Drug Administration FDA has approved ZEPATIER elbasvir and grazoprevir for the treatment of adult patients with chronic hepatitis C virus HCV genotype GT  or GT infection with or without ribavirin RBV following priority review by the FDA. ZEPATIER pronounced ZEPahteer is a oncedaily fixeddose combination tablet containing the NSA inhibitor elbasvir  mg and the NSA protease inhibitor grazoprevir  mg. The FDA previously granted two Breakthrough Therapy designations to ZEPATIER for the treatment of chronic HCV GT infection in patients with end stage renal disease on hemodialysis and for the treatment of patients with chronic HCV GT infection. Breakthrough Therapy designation is given to investigational medicines for serious or lifethreatening conditions that may offer substantial improvement over existing therapies. Across multiple clinical studies ZEPATIER achieved high rates of sustained virologic response ranging from  to  percent in GTinfected patients and  to  percent in GTinfected patients. Sustained virologic response is defined as HCV RNA levels measuring less than the lower limit of quantification at  weeks after the cessation of treatment SVR indicating that a patients HCV infection has been cured. ZEPATIER is not for use in patients with moderate or severe hepatic impairment ChildPugh B or C. ZEPATIER also is not for use with organic anion transporting polypeptides B OATPB inhibitors e.g. atazanavir darunavir lopinavir saquinavir tipranavir cyclosporine strong cytochrome P A CYPA inducers e.g. carbamazepine phenytoin rifampin St. Johns Wort and efavirenz. If ZEPATIER is administered with RBV healthcare professionals should refer to the prescribing information for RBV as the contraindications warnings and precautions adverse reactions and dosing for RBV also apply to this combination regimen.  Continued innovation is needed to help address the worldwide epidemic of chronic hepatitis C virus infection said Dr. Roger M. Perlmutter president Merck Research Laboratories. Our clinical program was designed to study a broad range of patients infected with the hepatitis C virus including difficulttotreat patients such as those with stage  or  chronic kidney disease. The approval of ZEPATIER is a testament to Mercks unwavering commitment to improving therapy for patients with hepatitis C virus infection and we are eager to bring this innovation to patients and physicians in the United States. ZEPATIER was approved with a treatment duration of  or  weeks depending on HCV genotype prior treatment history and for patients with GTa infection the presence of certain baseline NSA polymorphisms. A week oncedaily regimen is recommended for the vast majority of patients for whom ZEPATIER is indicated.  Mercks broad clinical trial program supporting the efficacy of ZEPATIER included six studies in  patients with chronic HCV GT or GT infection. These studies assessed the rate of sustained virologic response  weeks after the completion of treatment with ZEPATIER SVR. The clinical development program for ZEPATIER enrolled diverse groups of HCV GT and GTinfected patients including treatmentnave patients and those who had failed prior therapy with peginterferon alfa PegIFN and RBV as well as patients suffering with meaningful comorbidities and health complications such as compensated cirrhosis and HIV coinfection. GTinfected patients with severe renal impairment on hemodialysis and those who previously failed therapy with PegIFN and RBV in combination with an HCV NSA protease inhibitor boceprevir simeprevir or telaprevir also were studied. The following table provides a summary of clinical data that contributed to the efficacy assessment of ZEPATIER. The primary endpoint in each study was SVR. Please see section entitled Summary of Study Designs below for additional study design information including treatment arms and baseline characteristics. Clinical Studies Supporting Efficacy of ZEPATIER elbasvir and grazoprevir  Clinical Trials  Population  SVR nN  Treatment Regimen and Duration   GT   CEDGE TN  double blind placebo controlled  TN  cirrhosis    ZEPATIER   weeks   CEDGE COINFXN openlabel single arm  TN  cirrhosis  HIV coinfection     CSURFER double blind placebo controlled  TNTEa  cirrhosis  severe renal impairment       CEDGE TEd  openlabel comparative  TEb  cirrhosis  HIV coinfection         ZEPATIER  weeks   ZEPATIER   RBV   weeks   CSALVAGE  openlabel single arm  TEc  cirrhosis     ZEPATIER   RBV   weeks   GT   CSCAPE openlabel  CEDGE TN  CEDGE COINFXN  TN without cirrhosis  TN  cirrhosis  TN  cirrhosis  HIV coinfection    ZEPATIER   weeks   CEDGE TE  TEb  cirrhosis     ZEPATIER   RBV   weeks   TE treatmentexperienced TN treatmentnave. a Failed prior IFN or PegIFN  RBV. b Failed prior PegIFN  RBV. c Failed prior PegIFN  RBV  HCV NSA protease inhibitor PI boceprevir simeprevir or telaprevir. d CEDGE TE treatment outcomes for ZEPATIER with RBV for  weeks n or without RBV for  weeks n not shown because these regimens are not recommended in PegIFN  RBVexperienced GT patients.  Selected Safety Information about ZEPATIER elbasvir and grazoprevir  Elevations of alanine transaminase ALT to greater than  times the upper limit of normal ULN occurred in  of subjects generally at or after treatment week . These late ALT elevations were typically asymptomatic and most resolved with ongoing or completion of therapy. Healthcare professionals should perform hepatic lab testing on patients prior to therapy at treatment week  and as clinically indicated. For patients receiving  weeks of therapy additional hepatic lab testing should be performed at treatment week .  Patients should be instructed to consult their healthcare professional without delay if they have onset of fatigue weakness lack of appetite nausea and vomiting jaundice or discolored feces. Healthcare providers should consider discontinuing ZEPATIER if ALT levels remain persistently greater than  times ULN. ZEPATIER should be discontinued if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin alkaline phosphatase or international normalized ratio. Recommended Dosage Regimens and Durations for ZEPATIER elbasvir and grazoprevir  The dosing regimens and durations for treatment with oncedaily ZEPATIER for chronic HCV GT or GT infection in patients with or without cirrhosis HIV coinfection or renal impairment are as follows Patient Population  Treatment  Duration   GTa  Treatmentnave or PegIFNRBVexperienced without baseline NSA polymorphisms  ZEPATIER   weeks   GTa  Treatmentnave or PegIFNRBVexperienced with baseline NSA polymorphisms  ZEPATIER with RBV   weeks   GTb  Treatmentnave or PegIFNRBVexperienced ZEPATIER  weeks   GTa or GTb  PegIFNRBVPIexperienced  ZEPATIER with RBV  weeks   GT  Treatmentnave ZEPATIER  weeks   GT  PegIFNRBVexperienced ZEPATIER with RBV   weeks  Patients who have failed treatment with PegIFN  RBV.  NSA resistanceassociated polymorphisms at amino acid positions    or .  Patients who have failed treatment with PegIFNRBV  HCV NSA PI boceprevir simeprevir or telaprevir. For GTainfected PegIFNRBVPIexperienced patients with one or more baseline NSA resistanceassociated polymorphisms positions    or  the optimal ZEPATIERbased treatment regimen and duration of therapy has not been established.  In patients with GTa infection some hepatitis C viruses may contain mutations that can confer resistance to treatment. These are called resistanceassociated polymorphisms also referred to as resistanceassociated variants RAVs. GTa infection accounts for  percent of U.S. HCV cases. To help as many patients as possible to achieve SVR testing for NSA resistanceassociated polymorphisms positions    or  is recommended for GTainfected patients prior to starting treatment with ZEPATIER to determine the optimal dosage regimen and duration. In clinical trials of ZEPATIER  percent  of GTainfected U.S. study participants had these NSA resistanceassociated polymorphisms at baseline. A week regimen of ZEPATIER with RBV is recommended for GTainfected patients with these baseline NSA polymorphisms as described in the above table.  This approval provides patients and physicians with an additional treatment option that has the potential to cure many patients with chronic hepatitis C in the United States said Dr. Ira Jacobson site chair department of medicine Mount Sinai Beth Israel New York. ZEPATIER is a oncedaily singletablet directacting antiviral that has demonstrated high cure rates in genotype  and in genotype  including treatmentnave and treatmentexperienced patients with or without compensated cirrhosis and those with chronic kidney disease. The company anticipates that ZEPATIER will be available for shipping to wholesalers within seven business days. Chronic hepatitis C is a potentially devastating illness that can cause serious longterm health consequences for patients including reduced liver function liver failure or liver cancer said Michael Ninburg executive director Hepatitis Education Project Seattle. Today chronic hepatitis C is a curable condition for many patients and we are fortunate to have multiple therapeutic tools that can mitigate its impact. Selected Safety Information about ZEPATIER elbasvir and grazoprevir continued  The concomitant use of ZEPATIER with certain drugs may lead to possible clinically significant adverse reactions from greater exposure to ZEPATIER or concomitant drugs. Coadministration of ZEPATIER is not recommended with certain strong CYPA inhibitors e.g. ketoconazole or the cobicistatcontaining regimens of elvitegravircobicistatemtricitabinetenofovir disoproxil fumarate or alafenamide. Healthcare professionals should not exceed atorvastatin mgdaily or rosuvastatin mgdaily when given with ZEPATIER. If ZEPATIER is given with fluvastatin lovastatin or simvastatin healthcare professionals should give the lowest statin dose necessary and closely monitor for statinassociated adverse events. If ZEPATIER and tacrolimus are coadministered frequent monitoring of tacrolimus whole blood concentrations changes in renal function and tacrolimusassociated adverse events is recommended.  The concomitant use of ZEPATIER and certain drugs may cause significant decrease of elbasvir and grazoprevir plasma concentrations which may lead to reduced therapeutic effect of ZEPATIER and possible development of resistance. Coadministration of ZEPATIER is not recommended with moderate CYPA inducers e.g. nafcillin bosentan etravirine modafinil.  In subjects receiving ZEPATIER for  weeks the most commonly reported adverse reactions of all intensity greater than or equal to  in placebocontrolled trials were fatigue headache and nausea. In subjects receiving ZEPATIER with RBV for  weeks the most commonly reported adverse reactions of moderate or severe intensity greater than or equal to  were anemia and headache. Pricing Designed to Enable Broad Patient Access to ZEPATIER elbasvir and grazoprevir  The latest innovations in chronic HCV treatment that have become available over the past three years now including ZEPATIER provide the U.S. with an unprecedented opportunity to significantly reduce the burden of HCV. The scientific community believes that control of HCV infection may be possible and is actively working to achieve that goal by . A significant medical need remains it is estimated that less than one in five patients with chronic HCV infection are currently treated with thousands of new cases each year. ZEPATIER which received two Breakthrough Therapy designations for GT patients with end stage renal disease on hemodialysis and for GT patients and was thereafter approved by the FDA following priority review offers a highly effective option for a broad range of adult patients with chronic HCV GT or GT infection. Public reports indicate that net prices for the most commonly used directacting antiviral regimens are substantially lower than the list prices. However the majority of patients with chronic HCV have not yet been treated in some cases due to cost constraints. After considering these factors Merck has established a list price of  for a week regimen which the company believes to be in the range of net prices for other commonly used HCV directacting antiviral regimens at  weeks of therapy. Merck anticipates that this price as well as our comprehensive access strategy to seek broad coverage across commercial and public segments will help broaden and accelerate patient access to treatment and move us closer to our shared goal of reducing the burden of chronic HCV in the U.S. Mercks decadeslong commitment in chronic hepatitis C  and infectious diseases overall  has been to both scientific innovation and access said Robert McMahon president U.S. Market Global Human Health Merck. We are embracing this opportunity to partner with payers and physicians to enable as many appropriate patients to be treated as possible as quickly as possible. Financial Assistance Programs for Those Who Need Help With the Cost of Their Medicine  Merck also anticipates that the list price of ZEPATIER will result in lower outofpocket medication costs for some patients. Lower outofpocket costs alone do not necessarily reflect a cost advantage in the outcome of the condition treated because there are other variables that affect relative costs. The direct outofpocket costs to patients will vary depending on an individuals insurance plan.  Privately insured patients who have difficulty affording the copay set by their insurance plan may be eligible for significant copay assistance and may pay as little as  for each prescription. Maximum savings are limited and terms and conditions apply. Information is available at  http Merck anticipates that the website for ZEPATIER will be accessible within  hours of FDA approval.  Merck also offers assistance to patients who cannot afford ZEPATIER through Mercks yearold Patient Assistance Program. The Merck PAP provides certain Merck medicines free of charge to eligible patients. The Merck PAP for ZEPATIER is designed primarily for the uninsured who without our assistance could not afford their medication. Additionally for those patients whose insurance plan covers ZEPATIER but who still cannot afford their medication a request for an exception may be made if they meet certain financial medical andor insurance criteria. For more information about the Merck PAP please visit  http or call the Merck Patient Assistance Program at .  Summary of Study Designs  Clinical Trials for GT HCV  CEDGE TN was a randomized doubleblind placebocontrolled trial in treatmentnave patients with GT or GT infection with or without cirrhosis. Patients were randomized in a  ratio to ZEPATIER for  weeks immediate treatment group N or placebo for  weeks followed by openlabel treatment with ZEPATIER for  weeks deferred treatment group N. Among patients with GT infection randomized to the immediate treatment group the median age was  years range  to   of the patients were male  were white  were black or African American  were Hispanic or Latino mean body mass index was  kgm  had baseline HCV RNA levels greater than  IU per mL  had cirrhosis  had nonCC ILB alleles CT or TT and  had GTa and  had GTb chronic HCV infection.  CEDGE COINFECTION COINFXN was an openlabel singlearm trial in treatmentnave HIVHCV coinfected patients with GT or GT infection with or without cirrhosis. Patients received ZEPATIER for  weeks N. Among patients with GT infection the median age was  years range  to   of the patients were male  were white  were black or African American  were Hispanic or Latino mean body mass index was  kg per m  had baseline HCV RNA levels greater than  IU per mL  had cirrhosis  had nonCC ILB alleles CT or TT and  had GTa  had GTb and  had GTOther chronic HCV infection. CSURFER was a randomized doubleblind placebocontrolled trial in patients with GT infection with or without cirrhosis with chronic kidney disease CKD Stage  eGFR  mLmin. m or CKD Stage  eGFR  mLmin. m including patients on hemodialysis who were treatmentnave or who had failed prior therapy with IFN or PegIFN  RBV therapy. Patients were randomized in a  ratio to one of the following treatment groups elbasvir  mg once daily  grazoprevir  mg once daily for  weeks N immediate treatment group or placebo for  weeks followed by openlabel treatment with elbasvir  grazoprevir for  weeks N deferred treatment group. In addition  patients received openlabel elbasvir  grazoprevir for  weeks intensive pharmacokinetic PK group. Patients randomized to the immediate treatment group and intensive PK group had a median age of  years range  to   of the patients were male  were white  were black or African American  were Hispanic or Latino  had baseline HCV RNA levels greater than  IUmL  had cirrhosis and  had nonCC ILB alleles CT or TT. CEDGE TE was a randomized openlabel comparative trial in patients with GT or GT infection with or without cirrhosis with or without HCVHIV coinfection who had failed prior therapy with PegIFN  RBV therapy. Patients were randomized in a  ratio to one of the following treatment groups ZEPATIER for  weeks N ZEPATIER  RBV for  weeks N ZEPATIER for  weeks N or ZEPATIER  RBV for  weeks N. Among patients with GT infection the median age was  years range  to   of the patients were male  were white  were black or African American  were Hispanic or Latino mean body mass index was  kgm  had baseline HCV RNA levels greater than  IUmL  had cirrhosis  had nonCC ILB alleles CT or TT and  had GTa  had GTb and  had GTOther chronic HCV infection. CSALVAGE was an openlabel singlearm trial in patients with GT infection with or without cirrhosis who had failed prior treatment with boceprevir simeprevir or telaprevir in combination with PegIFN  RBV. Patients received elbasvir  mg once daily  grazoprevir  mg once daily  RBV for  weeks N. Patients had a median age of  years range  to   of the patients were male  were white  were black or African American  were Hispanic or Latino mean body mass index was  kgm  had baseline HCV RNA levels greater than  IUmL  had cirrhosis and  had nonCC ILB alleles CT or TT  had baseline NS resistanceassociated substitutions. Clinical Trials for GT HCV  The efficacy of ZEPATIER in patients with GT chronic HCV infection was demonstrated in CEDGE TN CEDGE COINFXN CEDGE TE and CSCAPE. CSCAPE was a randomized openlabel trial which included treatmentnave patients with GT infection without cirrhosis. Patients were randomized in a  ratio to elbasvir  mg once daily  grazoprevir  mg once daily for  weeks N or elbasvir  mg once daily  grazoprevir  mg once daily  RBV for  weeks N. In these combined studies in patients with GT infection  were treatmentnave  of the patients were male  were white  were black or African American  had cirrhosis and  had HIVHCV coinfection. About Merck  Todays 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  countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through farreaching policies programs and partnerships. For more information visit  http and connect with us on Twitter httpstwitter.comMerck Facebook http YouTube http and LinkedIn https ForwardLooking Statement of Merck  Co. Inc. Kenilworth NJ USA  This news release of Merck  Co. Inc. Kenilworth NJ USA the company includes forwardlooking statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of . These statements are based upon the current beliefs and expectations of the companys 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 forwardlooking 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 the companys ability to accurately predict future market conditions manufacturing difficulties or delays financial instability of international economies and sovereign risk dependence on the effectiveness of the companys patents and other protections for innovative products and the exposure to litigation including patent litigation andor regulatory actions.  The company undertakes no obligation to publicly update any forwardlooking 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 forwardlooking statements can be found in the companys  Annual Report on Form K and the companys other filings with the Securities and Exchange Commission SEC available at the SECs Internet site  http  Please see Prescribing Information for ZEPATIER elbasvir and grazoprevir at http_circularszzepatierzepatier_pi.pdf and the Patient Information for ZEPATIER at http_circularszzepatierzepatier_ppi.pdf"