Category Archives: Zepatier

DAA Linked to High Response in Vets With HCV

Posted on by May 3, 2017

A retrospective database analysis of U.S. veterans with hepatitis C virus and a high incidence of comorbidities showed that elbasvir-grazoprevir (Zepatier, Merck) achieved a high sustained virologic response (SVR) rate, according to a presentation at the International Liver Congress 2017, in Amsterdam.

The researchers conducted the analysis of 2,436 chronic HCV patients in the Department of Veterans Affairs (VA) health care system, identified from the VA Corporate Data Warehouse, a national repository of VA electronic medical records. The patients were treated with elbasvir-grazoprevir between Feb. 1, 2016 and Aug. 1, 2016. Study outcomes included real-world use and SVR rates.

“U.S. veterans are three times more likely to have chronic hepatitis C compared with the general U.S. population, and a high proportion suffer comorbid conditions that can make treatment challenging,” said Jennifer Kramer, from Michael E. DeBakey VA Medical Center, and an assistant professor of medicine, Department of Medicine, Baylor College of Medicine, both in Houston, and a study investigator. “This study shows that chronic hepatitis C antiviral treatment can result in a high rate of sustained virologic response in U.S. veterans.”

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Real-World Observational Study in the U.S. Veterans Affairs System Evaluating Use of Merck’s ZEPATIER® (Elbasvir and Grazoprevir) Shows High Sustained Virologic Response Rates in Patients with Chronic Hepatitis C

Posted on by April 21, 2017

Release Date: Friday, April 21, 2017 10:00 am EDT

Dateline City:
KENILWORTH, N.J.

Study Evaluated VA Population with High Incidence of Co-Morbidities

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the presentation of findings from a retrospective database analysis of patients with chronic hepatitis C virus (HCV) infection who were administered ZEPATIER® in the U.S. Department of Veterans Affairs (VA) healthcare system. For the evaluable population (n=2,436), 95.6 percent of veterans treated with ZEPATIER achieved the primary outcome of sustained virologic response (SVR), defined as undetectable HCV RNA at least twelve weeks after the end of treatment. For patients with no HCV RNA measurements at or after 12 weeks (19% of the study cohort), the analysis used HCV RNA measurements available at least four and less than 12 weeks after the end of treatment. The response rates in the real-world setting of the VA supplement the overall findings from the controlled clinical studies of ZEPATIER. These findings will be presented today in an oral session (abstract #PS-095) at The International Liver Congress™ 2017 being held in Amsterdam, the Netherlands.

In the United States, ZEPATIER is indicated for the treatment of chronic HCV GT1 or GT4 infection in adults. ZEPATIER is indicated for use with ribavirin (RBV) in certain patient populations. The U.S. Prescribing Information for ZEPATIER includes a Boxed Warning about the risk of hepatitis B virus (HBV) reactivation in patients co-infected with HCV and HBV. In controlled clinical studies of ZEPATIER, SVR was the primary endpoint defined as HCV RNA less than lower limit of quantification (LLOQ) at 12 weeks after the cessation of treatment (SVR12).

“U.S. veterans are three times more likely to have chronic hepatitis C compared to the general U.S. population and a high proportion suffer co-morbid conditions that can make treatment challenging,” said Jennifer Kramer, investigator, Michael E. DeBakey VA Medical Center, Houston, Texas, and assistant professor of medicine, department of medicine, Baylor College of Medicine. “This study shows that chronic hepatitis C antiviral treatment can result in a high rate of sustained virologic response in U.S. veterans.”

This retrospective database analysis included patients with chronic HCV treated with ZEPATIER (elbasvir and grazoprevir) in the VA healthcare system between February 1, 2016 and August 1, 2016. Study outcomes include real-world utilization and SVR rates. Please see additional information about the design, methodology and limitations of this observational study below.

After applying study exclusion criteria, 2,436 patients were included in the evaluable population cohort. The mean age of subjects was 63.5 years. The prevalence of co-morbidities as determined by ICD-9 and CPT codes as recorded in the VA database was as follows: cirrhosis (33.2%), diabetes (53.2%), depression (57.2%) and HIV co-infection (3%). Additionally, more than half of the patients had a history of drug (53.9%) or alcohol (60.5%) abuse. The population included 1,988 previously untreated patients and 448 treatment-experienced patients (322 of whom previously received an interferon-based regimen with or without an NS3/4A HCV protease inhibitor, and 126 of whom previously received an interferon-free direct-acting antiviral regimen).

A total of 95.6 percent (2,328/2,436) of patients in the evaluable population achieved SVR following treatment with ZEPATIER. The SVR rates by genotype (GT) were as follows: all GT1, 95.4 percent (2218/2324); GT1a, 93.4 percent (788/844); GT1b, 96.6 percent (1379/1428); and GT4, 96.9 percent (62/64). The SVR rates by baseline viral load (BVL) were as follows: BVL greater than 800,000 IU/ml, 94.7 percent (1497/1580); and BVL less than or equal to 800,000 IU/ml, 97.3 percent (726/746).

The SVR rates by baseline patient characteristics were as follows: male, 95.5 percent (2,245/2,350); female, 96.5 percent (83/86); African American, 95.9 percent (1,342/1,400); Hispanic, 95.1 percent (77/81); White, 95.0 percent (783/824); previously untreated, 96.1 percent (1,910/1,988); treatment-experienced, 93.3 percent (418/448); cirrhosis, 95.5 percent (772/808); without cirrhosis, 95.6 percent (1556/1628); stage 3 chronic kidney disease (CKD) (eGFR 30 to 59 mL/min/1.73m2), 96.7 percent (380/393); stage 4-5 CKD (eGFR less than 30 mL/min/1.73m2), 96.3 percent (392/407); HIV positive, 98.6 percent (73/74); HIV negative, 95.5 percent (2255/2362); history of alcohol abuse, 95.9 percent (1412/1473); no history of alcohol abuse, 95.1 percent (916/963); history of drug abuse, 95.3 percent (1251/1313); no history of drug abuse, 95.9 percent (1077/1123).

Adverse event data were not collected as part of this real-world data analysis.

“Analysis of data from real-world medical settings can provide useful insights to supplement knowledge gained from randomized clinical trials,” said Susan Shiff, senior vice president, center for observational and real-world evidence, Merck. “These data from a real-world VA setting add to the body of evidence on ZEPATIER (elbasvir and grazoprevir) and help deepen scientific understanding of the treatment of this complex disease affecting diverse, sometimes difficult to treat, patient populations.”

Study Methodology

Patients with chronic HCV treated with ZEPATIER from February 1 to August 1, 2016 were identified from the VA Corporate Data Warehouse, a national repository of VA electronic medical records. Inclusion criteria specified initiation of ZEPATIER therapy, at least 18 years of age, positive HCV RNA, and at least one inpatient or outpatient visit within a one-year period prior to treatment initiation (n=2,985). Patients were excluded if they had RBV added greater than one month after treatment initiation (n=23). Patients without SVR data or on-treatment HCV RNA data (n=494), or those treated with ZEPATIER for greater than seventeen weeks (n=32), were excluded as well. The total number of patients in the evaluable population was 2,436.

SVR was assessed based on undetectable HCV RNA at least twelve weeks after the end of treatment. For patients with no HCV RNA measurements at or after 12 weeks, the analysis used HCV RNA measurements available at least four and less than 12 weeks after the end of treatment. SVR was evaluated based on HCV RNA measurement at least 12 weeks post treatment in 81 percent of the study population.

About Real-World Data Analyses and Associated Limitations

Real-world studies analyze data generated outside of randomized clinical trials, such as through analyses of electronic medical records or claims databases, to provide insight into how medicines perform or are used from a clinical and economic viewpoint in real-world clinical settings. Information from real-world analyses alone does not provide sufficient evidence to validate efficacy or safety of a therapeutic regimen and does not provide a substitute for evidence obtained from randomized controlled clinical trials.

This study is subject to certain limitations. The VA population may not be generalizable to the entire U.S. population, due in part to the potential for a differing demographic make-up and/or risk factors. Bias may exist as diagnoses and co-morbidities were identified through ICD-9 and CPT codes. Treatment completion was identified through prescription records which may not reflect adherence. Database analyses are also prone to errors in coding and missing data, including unavailable SVR data at or after the 12-week post-treatment time point. Additionally, some laboratory data including data on the presence of baseline NS5A resistance associated substitutions was not available at the time of this analysis.

About the VA Corporate Data Warehouse (CDW)

The Department of Veterans Affairs Veterans Healthcare Administration (VHA) is supported by one of the largest integrated healthcare information systems in the United States. The VHA’s Corporate Data Warehouse (CDW) was developed in 2006 to accommodate the massive amounts of data being generated from more than 20 years of use and to streamline the process of knowledge discovery to application.

About ZEPATIER ® (elbasvir and grazoprevir) 50mg/100mg Tablets

ZEPATIER is a fixed-dose combination product containing elbasvir, a HCV NS5A inhibitor, and grazoprevir, an HCV NS3/4A protease inhibitor. In the United States, ZEPATIER is indicated for the treatment of chronic HCV GT1 or 4 infection in adults. ZEPATIER is indicated for use with ribavirin (RBV) in certain patient populations. The efficacy of ZEPATIER has not been established in patients who have previously failed treatment with other regimens that included an NS5A inhibitor.

Selected Safety Information about ZEPATIER

The US Prescribing Information for ZEPATIER contains a Boxed Warning about the risk of hepatitis B virus (HBV) reactivation in patients coinfected with HCV and HBV. Healthcare professionals should test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating treatment with ZEPATIER. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Healthcare professionals should monitor HCV/HBV coinfected patients for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Healthcare professionals should initiate appropriate patient management for HBV infection as clinically indicated.

HBV reactivation has been reported in HBsAg positive patients and also in patients with serologic evidence of resolved HBV infection (ie, HBsAg negative and anti-HBc positive). The risk of HBV reactivation may be increased in patients receiving some immunosuppressant or chemotherapeutic agents. HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level. In patients with resolved HBV infection, reappearance of HBsAg can occur. Reactivation of HBV replication may be accompanied by hepatitis, ie, increases in aminotransferase levels and, in severe cases, increases in bilirubin levels, liver failure, and death can occur.

ZEPATIER (elbasvir and grazoprevir) is not for use in patients with moderate or severe hepatic impairment (Child Pugh B or C). ZEPATIER is also not for use with inhibitors of organic anion transporting polypeptides 1B1/3 (OATP1B1/3) that are known or expected to significantly increase grazoprevir plasma concentrations (e.g., atazanavir, darunavir, lopinavir, saquinavir, tipranavir, cyclosporine), strong cytochrome P450 3A (CYP3A) inducers (e.g., carbamazepine, phenytoin, rifampin, St. John’s Wort), and efavirenz. If ZEPATIER (elbasvir and grazoprevir) 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.

Elevations of alanine transaminase (ALT) to greater than 5 times the upper limit of normal (ULN) occurred in 1% of subjects, generally at or after treatment week 8. 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 8, and as clinically indicated. For patients receiving 16 weeks of therapy, additional hepatic lab testing should be performed at treatment week 12.

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 (elbasvir and grazoprevir) if ALT levels remain persistently greater than 10 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.

The concomitant use of ZEPATIER with certain drugs may lead to adverse reactions or reduced therapeutic effect due to drug interactions. Certain strong CYP3A inhibitors may increase the plasma concentration of ZEPATIER, leading to possibly clinically significant adverse reactions. Moderate CYP3A inducers may decrease the plasma concentration of ZEPATIER, leading to reduced therapeutic effect and possible development of resistance. Coadministration of ZEPATIER with these drugs is not recommended. Physicians should consult the Prescribing Information for potential drug interactions.

In subjects receiving ZEPATIER for 12 weeks, the most commonly reported adverse reactions of all intensity (greater than or equal to 5% in placebo-controlled trials) were fatigue, headache and nausea. In subjects receiving ZEPATIER with RBV for 16 weeks, the most commonly reported adverse reactions of moderate or severe intensity (greater than or equal to 5%) were anemia and headache.

Selected Dosage and Administration Information for ZEPATIER ® (elbasvir and grazoprevir)

ZEPATIER is a single tablet taken once daily. The recommended dosing is 12 or 16 weeks with or without RBV, depending on HCV genotype, prior treatment history and, for patients with genotype 1a infection, presence of certain baseline NS5A resistance-associated polymorphisms. See Prescribing Information for ZEPATIER for specific dosage regimens and durations. Refer to RBV prescribing information for RBV dosing and dosage modifications when ZEPATIER is given with RBV. To determine dosage regimen and duration of ZEPATIER for genotype 1a patients, testing for the presence of virus with one or more baseline NS5A resistance-associated polymorphisms at positions 28, 30, 31, or 93 is recommended prior to initiating treatment.

Merck’s Commitment to HCV

For more than 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck’s chronic HCV clinical development programs have included more than 135 clinical trials in approximately 40 countries and have enrolled nearly 10,000 participants. As part of our longstanding leadership in infectious diseases, Merck collaborates with the scientific and patient communities to develop and deliver innovative solutions to support people living with chronic HCV worldwide.

About Merck

For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been bringing forward medicines and vaccines for many of the world’s most challenging diseases. 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. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world – including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) 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 the company’s management and are subject to significant risks and uncertainties. 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; the company’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 the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company 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 the company’s 2016 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).

Please see Prescribing Information for ZEPATIER (elbasvir and grazoprevir) at http://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_pi.pdf and the Patient Information for ZEPATIER at http://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_ppi.pdf

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Contact:

Merck & Co., Inc.
Media:
Doris Li, 908-740-1903
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Safety and Efficacy of Elbasvir/Grazoprevir in Patients with Hepatitis C Virus Infection and Compensated Cirrhosis: an Integrated Analysis—Ira M. Jacobson et al.

Posted on by March 21, 2017

Article: Safety and Efficacy of Elbasvir/Grazoprevir in Patients with Hepatitis C Virus Infection and Compensated Cirrhosis: an Integrated Analysis—Ira M. Jacobson et al.

Source: http://dx.doi.org/10.1053/j.gastro.2017.01.050

 Study Aims and Results

This was a retrospective study—looking back at prior studies—to analyze the results of Merck’s two drug combination of elbasvir plus grazoprevir (Zepatier) with or without ribavirin to treat patients infected with chronic hepatitis C who had compensated cirrhosis.  The study combined data from 6 clinical studies.

Conclusion

The analysis of the studies included 402 patients with HCV genotype 1, 4, or 6.  The patients were treated for 12 to 18 weeks.  The goal of the study was to find the number of people who were cured of hepatitis C.

In those who received Zepatier (without ribavirin) 97.8% (135 of 138 patients) of treatment-naïve and 88.9% (48 of 54 pts) of treatment-experienced were cured of hepatitis C.

In those who received Zepatier for 12 weeks the addition of ribavirin did not increase the cure rates—treatment naïve-90.3% (28 of 31 pts) or treatment experienced -91.4% (74 of 81 pts).

All of the patients who received Zepatier and ribavirin for 16 or 18 weeks were cured, and 93.9% (46 of 49 pts) of patients were cured who received Zepatier without ribavirin treated for 16 or 18 weeks.

People with HCV genotype 1a infection and those who had not responded to a previous course of interferon therapy were less likely to be cured compared to those with HCV genotype 1b.  Baseline testing for resistant associated variants was recommended to ascertain the best course of treatment duration and if the addition of ribavirin is needed for treatment of HCV genotype 1a.  Patients with the baseline RAVs had a 73% (8 of 11 pts) cure rate compared to a 98% (96 of 98 pts) cure rate in those who did not have baseline RAVs.  The patients who had HCV genotype 1a infection with baseline RAVs who received 16 or 18 weeks of Zepatier plus ribavirin were cured reinforcing the need for ribavirin to overcome baseline RAVs.

There were 3% of serious adverse events but they did not lead to a decompensated event.

 Editorial Comments

The pooled analysis of Zepatier clinical studies of people with compensated cirrhosis showed very high cure rates, low side effect profile and in the vast majority of cases no ribavirin is needed.  From this analysis the only cases that ribavirin may be of benefit is in patients with HCV genotype 1a baseline RAVs.

To read the entire newsletter, click here

Alan Franciscus is the Executive Director of the Hepatitis C Support Project and the Editor-in-Chief of the HCV Advocate Website.

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ZEPATIER® now covered in Quebec for the treatment of chronic hepatitis C

Posted on by March 21, 2017

KIRKLAND, QC, March 21, 2017 /CNW Telbec/ – Merck Canada Inc. today announced that ZEPATIER® (elbasvir/grazoprevir) will be listed among the drugs covered by Quebec’s health insurance board, the Régie de l’assurance maladie du Québec (RAMQ), as of March 22. Quebec joins other jurisdictions that have approved the product for reimbursement under their public healthcare plans for chronic hepatitis C patients presenting with recognized criteria. Zepatier is indicated for the treatment of chronic infection by genotypes 1, 3 or 4 of the hepatitis C virus in adults.1 The product monograph, including detailed product information and indication, is available online by clicking here.

“This announcement reflects the hepatitis C agreement between Merck and the pan-Canadian Pharmaceutical Alliance (pCPA). We are proud to contribute a solution in the fight against this disease, all the while helping reduce the cost pressure on the healthcare system,” says Chirfi Guindo, President and Managing Director of Merck Canada Inc.

Hepatitis C patients without significant hepatic fibrosis who present with certain comorbidities or specific conditions will be eligible for the treatment, including those who have chronic kidney disease, who are co-infected with the human immunodeficiency virus (HIV) or the hepatitis B virus (HBV), who have undergone an organ transplant or who present with extrahepatic manifestations of the disease.

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Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Kidney Transplants From Hepatitis C-Positive Donors (HCV)

Posted on by December 9, 2016

I am posting this study again.  I added a short inspirational video from the University of Pennsylvania, click here….

Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Kidney Transplants From Hepatitis C-Positive Donors (HCV)

There is a tremendous shortage of kidneys needed for transplants.  In a first of its kind study, a hepatitis C (HCV) infected kidney is being transplanted into HCV-negative persons and being treated with Zepatier.  Treatment is occurring after a single kidney transplant.

University of Pennsylvania: Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Kidney Transplants From Hepatitis C-Positive Donors (HCV)

To read the entire clinical trial description, click here…

 

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Hepatitis C Cure Rate 93% With Elbasvir/Grazoprevir for Genotype 1 or 4 | Mark Mascolini

Posted on by December 1, 2016

Sustained virologic response 12 weeks after elbasvir/grazoprevir (EBR/GZR, Zepatier) therapy ended (SVR12) reached 93% among HCV genotype 1 and 4 patients in the double-blind, placebo-controlled C-CORAL trial. SVR12 rates did not differ by sex, age or fibrosis stage.

HCV prevalence in the Asia/Pacific region and Russia ranges from 1% to 5%, with genotype 1b accounting for about half of infections. Fixed-dose one-tablet once-daily EBR/GZR is licensed for treatment of genotype 1 and 4 HCV in the United States, the European Union and elsewhere. C-CORAL collaborators conducted this trial to assess EBR/GZR efficacy and safety in Korea, Taiwan, Vietnam, Thailand, Australia and Russia. EBV is an NS5A inhibitor, and GZR is an NS3/4A protease inhibitor.

The phase 3 trial randomized 250 participants to immediate EBR/GZR and 86 to placebo for 12 weeks, followed by unblinding and EBR/GZR for the placebo group. All patients had HCV genotype 1, 4 or 6 and none had HIV; they could have compensated cirrhosis. The primary endpoint was SVR12 in the immediate EBR/GZR arm.

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Merck Announces Findings for Investigational Triple-Combination Chronic Hepatitis C Therapy Showing High Rates of Sustained Virologic Response in People with Genotypes 1, 2 or 3 Infection

Posted on by November 13, 2016

Phase 2 Data Presentations at The Liver Meeting ® Detail SVR12 Rates from Two Studies as Well as SVR8 Rates in Patients for Whom Direct-Acting Antiviral Treatment Previously Failed

Sunday, November 13, 2016 8:00 am EST
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KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced the presentation of results from three Phase 2 clinical trials evaluating MK-3682B (MK-3682/grazoprevir/ruzasvir1), the company’s investigational all-oral, triple-combination regimen for the treatment of chronic hepatitis C (HCV) infection (informally referred to as MK3). Results from Part B of C-CREST 1 & 2 demonstrated high rates of sustained virologic response2 (SVR) 12 weeks after the completion of therapy (SVR12, considered virologic cure) in patients with chronic HCV genotype (GT) 1 or GT3 infection who received eight weeks of treatment with MK-3682B. Findings from C-CREST 1 & 2 Part B also demonstrated high rates of SVR12 in GT1, GT2 and GT3-infected patients who received MK3 for 12 or 16 weeks. Findings from Part C of C-CREST 1 & 2 and interim results from the ongoing C-SURGE study showed high rates of SVR12 and SVR8, respectively, in chronic HCV patients who had failed prior treatment with investigational or approved direct-acting antiviral regimens. These results will be announced in oral presentations at The Liver Meeting® 2016 today (C-CREST 1 & 2 Parts B and C) and tomorrow (C-SURGE).

“Across the chronic hepatitis C treatment landscape, incredible progress has been made in a remarkably short amount of time, but there remains a need for more options, particularly for patients who do not achieve sustained virologic response with treatment regimens available today,” said Dr. Eliav Barr, senior vice president, global clinical development, infectious diseases and vaccines, Merck Research Laboratories. “The strong findings observed following treatment with MK-3682B are an encouraging step towards Merck’s goal of developing and delivering a shorter-duration, pan-genotypic next-generation treatment regimen for more patients with chronic hepatitis C infection.”

C-CREST 1 & 2 Part B Overview and Findings

Part B of C-CREST 1 & 2 – ongoing, open-label Phase 2 clinical trials – was designed to evaluate the safety and efficacy of MK-3682B in patients with chronic HCV GT1, GT2 or GT3 infection, with or without cirrhosis. Patients with GT2 or GT3 infection received MK-3682B with or without RBV. All patients with GT1 or GT2 infection were treatment-naïve. Fifty six percent (189/337) of patients with GT3 infection were treatment naïve and 44 percent (148/337) were previously treated with peginterferon/ribavirin (RBV). The primary endpoint of the study was the proportion of patients in each treatment arm who achieved SVR12.

Eight weeks of treatment with MK-3682B resulted in SVR12 rates of 95 percent, 86 percent and 95 percent in GT1, GT2 and GT3 patients, respectively. A 12-week treatment duration resulted in high SVR12 rates in all genotypes (GT1, 99%; GT2, 97%; GT3, 97%). Efficacy was comparable in patients with and without cirrhosis. There were no virologic failures in the patients with GT1 or GT2 infection who received 12 weeks of MK-3682B. Efficacy results are presented in the table below. Results from Part A of C-CREST 1 & 2 were previously reported at The Liver Meeting® in November 2015.

Summary of SVR12 Findings
Population N MK-3682B

+/- RBV

8 weeks

 MK-3682B

+/- RBV

12 weeks

 MK-3682B

+/- RBV

16 weeks
GT1a 90 93% (39/42) 98% (47/48) –
GT1b 86 98% (45/46) 100% (40/40) –
GT2 151 86% (54/63) 97% (60/62) 100% (26/26)
GT3* 337 95% (98/103) 97% (155/159) 96% (72/75)

*28 percent (29/103), 36 percent (58/159) and 81 percent (61/75)
of patients with GT3 infection receiving eight, 12 or 16 weeks
of therapy, respectively, were previously treated with peginterferon/RBV

Among patients who received at least one dose of MK-3682B with or without RBV, the overall most common adverse events (AEs) reported (greater than 10% incidence in either treatment arm) were headache (22%), fatigue (19%) and nausea (13%). There were two drug-related serious AEs, both considered related to RBV only. Nine patients discontinued study drug due to AEs, four of whom discontinued RBV only. One patient died due to AEs not related to the study drug.

“As a scientist and physician who regularly treats patients with chronic hepatitis C, the importance of continuing to research this complex disease and its many complications is evident,” 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. “The virologic cure rates observed in Part B of C-CREST 1 & 2 clearly demonstrate the potential for MK3 and support further study of this investigational regimen.”

C-SURGE Overview and Preliminary Findings

C-SURGE is an ongoing, open-label Phase 2 clinical trial designed to evaluate MK-3682B with or without RBV in chronic HCV GT1 patients who previously failed therapy with either ledipasvir/sofosbuvir (LDV/SOF) or ZEPATIER™ (elbasvir and grazoprevir). The study enrolled 94 patients randomized to receive 16 weeks of MK-3682B plus RBV (n=45) or 24 weeks of MK-3682B without ribavirin (n=49); one patient in the 16 week arm withdrew prior to starting treatment. Of the 93 patients who received treatment in this study, 61 percent (57/93) had previously received 12 to 24 weeks of treatment with LDV/SOF; 15 percent (14/93) had received 8 weeks of LDV/SOF; and 24 percent (22/93) had received 12 weeks of ZEPATIER. A majority of patients (84%, 78/93) had at least one baseline NS5A resistance-associated variant (RAV) at positions 28, 30, 31 or 93.

Interim results from the modified full analysis set (mFAS), which excludes one patient in the 16-week arm who withdrew due to administrative reasons after receiving three doses of study medication, show all patients (43/43) who have completed treatment with MK-3862B plus RBV for 16 weeks achieved SVR8. All patients (49/49) in the mFAS who received MK-3682B for 24 weeks have completed treatment and remain subject to follow-up; the interim results show of those in the 24-week arm who have reached follow-up weeks four and eight, 100 percent have achieved SVR4 (38/38) and SVR8 (30/30), respectively. SVR12 is the primary outcome measure of this ongoing trial. Final results will be presented at a future scientific congress.

Among patients who received at least one dose of MK-3682B with or without RBV, the overall most common AEs reported were fatigue (35%), headache (13%), diarrhea (9%), rash (9%) and pruritus (5%). There were no drug-related serious AEs, and no patients discontinued due to a drug-related AE.

C-CREST 1 & 2 Part C Overview and Findings

Part C of C-CREST 1 & 2 was designed to evaluate retreatment with MK-3682B plus RBV for 16 weeks among patients who previously failed an investigational triple-therapy regimen (MK-3682/grazoprevir/ruzasvir or MK-3682/grazoprevir/elbasvir). The study enrolled 24 patients with GT1 (n=2), GT2 (n=14) or GT3 (n=8) infection. All patients (23/23) who completed treatment achieved SVR12. One GT2 patient discontinued treatment after a single dose due to drug-related serious AEs. Among patients who received at least one dose of MK-3682B plus RBV, the most common AEs reported (greater than 20% incidence) were headache (33%), fatigue (25%), nausea (25%), rash (21%) and insomnia (21%).

About MK-3682B

MK-3682B (informally referred to as MK3) is Merck’s investigational triple-combination therapy in Phase 2 development for the treatment of chronic HCV infection. MK-3682B combines an HCV nucleotide analogue NS5B polymerase inhibitor (MK-3682), an HCV NS3/4A protease inhibitor (grazoprevir, MK-5172) and an HCV NS5A inhibitor (ruzasvir, MK-8408).

About ZEPATIER™ (elbasvir and grazoprevir) 50 mg/100mg tablets

ZEPATIER is a fixed-dose combination product containing elbasvir, an HCV NS5A inhibitor, and grazoprevir, an HCV NS3/4A protease inhibitor. ZEPATIER is indicated with or without ribavirin (RBV) for treatment of chronic HCV genotypes 1 or 4 infection in adults.

Selected Safety Information about ZEPATIER

ZEPATIER is not for use in patients with moderate or severe hepatic impairment (Child Pugh B or C). ZEPATIER is also not for use with organic anion transporting polypeptides 1B1/3 (OATP1B1/3) inhibitors (e.g., atazanavir, darunavir, lopinavir, saquinavir, tipranavir, cyclosporine), strong cytochrome P450 3A (CYP3A) inducers (e.g., carbamazepine, phenytoin, rifampin, St. John’s 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.

Elevations of alanine transaminase (ALT) to greater than 5 times the upper limit of normal (ULN) occurred in 1% of subjects, generally at or after treatment week 8. 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 8, and as clinically indicated. For patients receiving 16 weeks of therapy, additional hepatic lab testing should be performed at treatment week 12.

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 10 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.

The concomitant use of ZEPATIER with certain drugs may lead to adverse reactions or reduced therapeutic effect due to drug interactions. Certain strong CYP3A inhibitors may increase the plasma concentration of ZEPATIER, leading to possibly clinically significant adverse reactions. Moderate CYP3A inducers may decrease the plasma concentration of ZEPATIER, leading to reduced therapeutic effect and possible development of resistance. Coadministration of ZEPATIER with these drugs is not recommended. Physicians should consult the Prescribing Information for potential drug interactions.

In subjects receiving ZEPATIER for 12 weeks, the most commonly reported adverse reactions of all intensity (greater than or equal to 5% in placebo-controlled trials) were fatigue, headache and nausea. In subjects receiving ZEPATIER with RBV for 16 weeks, the most commonly reported adverse reactions of moderate or severe intensity (greater than or equal to 5%) were anemia and headache.

Selected Dosage and Administration Information for ZEPATIER (elbasvir and grazoprevir)

ZEPATIER is a single tablet taken once daily. The recommended dosing is 12 or 16 weeks with or without RBV, depending on HCV genotype, prior treatment history and, for patients with genotype 1a infection, presence of certain baseline NS5A resistance-associated polymorphisms. See Prescribing Information for ZEPATIER for specific dosage regimens and durations. Refer to RBV prescribing information for RBV dosing and dosage modifications when ZEPATIER is given with RBV. To determine dosage regimen and duration of ZEPATIER for genotype 1a patients, testing for the presence of virus with one or more baseline NS5A resistance-associated polymorphisms at positions 28, 30, 31, or 93 is recommended prior to initiating treatment.

Merck’s Commitment to HCV

For more than 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck’s chronic HCV clinical development programs have included more than 135 clinical trials in approximately 40 countries and have enrolled nearly 10,000 participants. As part of our longstanding leadership in infectious diseases, Merck collaborates with the scientific and patient communities to develop and deliver innovative solutions to support people living with chronic HCV worldwide.

About Merck

For 125 years, Merck has been 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, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) 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 the company’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; the company’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 the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company 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 the company’s 2015 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).

Please see Prescribing Information for ZEPATIER (elbasvir and grazoprevir) at http://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_pi.pdf and the Patient Information for ZEPATIER at http://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_ppi.pdf

1 MK-3682 is an HCV nucleotide analogue NS5B polymerase inhibitor. Grazoprevir (MK-5172) is an HCV NS3/4A protease inhibitor. Ruzasvir (MK-8408) is an HCV NS5A inhibitor.

2 Measured as HCV RNA less than 15 IU/mL.

Contact:

Media:
Doris Li, 908-246-5701
or
Sarra Herzog, 201-669-6570
or
Investors:
Teri Loxam, 908-740-1986
or
Amy Klug, 908-740-1898

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Bid to speed transplants with hepatitis C-infected kidneys | LAURAN NEERGAARD, AP Medical Writer

Posted on by October 27, 2016

Some patients facing a years-long wait for a kidney transplant are jumping ahead in line thanks to a startling experiment: They’re agreeing to an organ sure to infect them with hepatitis C

WASHINGTON (AP) — Some patients facing a years-long wait for a kidney transplant are jumping ahead in line thanks to a startling experiment: They’re agreeing to an organ almost sure to infect them with hepatitis C.

Knowingly transmitting a dangerous virus may sound drastic but two leading transplant centers are betting the strategy will save lives — if new medications that promise to cure hepatitis C allow use of organs that today go to waste.

Read more…

Read about the clinical trial on our Clinical Trial Reference Guide click here….

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