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

Austria, Europe, North America, United States

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

23/04/2015 — VIENNA — (BUSINESS WIRE)

MSD, known as Merck (NYSE:MRK) in the United States and Canada, today announced the first presentation of data from C-SURFER, the companys 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 CongressTM 2015 the 50th 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, U.S.A. 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 randomised 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 haemodialysis 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.

MSDs 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, a U.S.-based division of Merck & Co., Inc., Kenilworth, N.J., U.S.A. 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 MSDs investigational grazoprevir plus elbasvir in patients infected with chronic HCV GT1 and with advanced chronic kidney disease (stages 4 and 5, including patients on haemodialysis) 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 MSDs broad clinical trials programme, 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.

MSDs Commitment to HCV

For nearly 30 years, MSD has been at the forefront of the response to the HCV epidemic. MSD 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 MSD

Today’s MSD is a global health care leader working to help the world be well. MSD is a tradename of Merck & Co., Inc., with headquarters in Kenilworth, N.J., U.S.A. 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.msd.com.

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 MSDs 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 materialise, 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; MSDs 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 & Co., Inc. group entity patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

MSD 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 MSDs 2014 Annual Report on Form 10-K and the companys other filings with the Securities and Exchange Commission (SEC) available at the SECs Internet site (www.sec.gov).

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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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