Public Release: 

Once-daily grazoprevir/elbasvir is effective in patients infected with chronic hepatitis C

Positive results from the Phase 3 C-EDGE TN study in treatment-naive patients

European Association for the Study of the Liver

April 24, 2015, Vienna, Austria: Results presented today at The International Liver Congress™ 2015 show that a 12-week oral regimen of once-daily single tablet grazoprevir/elbasvir (GZR/EBR) is effective and well-tolerated in treatment-naive (TN) patients infected with chronic hepatitis C virus (HCV) genotypes (GT)-1, -4 or -6, including those with compensated cirrhosis.

Based on preliminary results from 316 GZR/EBR recipients in the immediate treatment arm, 299 patients (95%) achieved a sustained virologic response at 12 weeks (SVR12).

"These initial results show that once-daily grazoprevir/elbasvir offers significant advantages over older treatments, demonstrating the ideal combination of high efficacy with good tolerability and convenience in treatment-naive patients infected with chronic HCV," said Rajender Reddy, MD, FAASLD Professor of Medicine, Professor of Medicine in Surgery, Director of Hepatology, Medical Director of Liver Transplantation, University of Pennsylvania, USA.

Serious adverse events (AEs) occurred in 9 (3%) and 3 (3%) patients in the active (immediate treatment) and placebo (deferred treatment) arms, respectively.

"Newer antiviral regimens such as the combination of grazoprevir/elbasvir offer much hope to people living with hepatitis C. They have shown great efficacy and tolerability for the treatment of this chronic infection," said Dr Laurent Castera, Vice-Secretary, European Association for the Study of the Liver.

C-EDGE TN is an international, randomised, blinded, placebo-controlled, parallel-group trial of an oral fixed-dosed combination of GZR 100 mg/EBR 50 mg once-daily in TN patients infected with HCV GT-1, -4 or -6, including cirrhotic and non-cirrhotic patients.

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About The International Liver Congress™

This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. 2015 is a very special year for EASL and the hepatology community as they will celebrate the 50th annual meeting. The International Liver Congress™ takes place from April 22-26, 2015, Vienna, Austria.

About EASL

Since EASL's foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from more than 100 countries around the world. EASL is the leading liver association in Europe, it attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

Contact

For more information, please contact the ILC Press Office at:

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+44 (0)20 3580 5444

THE PHASE 3 C-EDGE TREATMENT-NAÏVE (TN) STUDY OF A 12-WEEK ORAL REGIMEN OF GRAZOPREVIR (GZR, MK-5172)/ELBASVIR (EBR, MK-8742) IN PATIENTS WITH CHRONIC HCV GENOTYPE (GT) 1, 4, OR 6 INFECTION

Stefan Zeuzem* 1, Reem Ghalib2, K. R. Reddy3, Paul J. Pockros4, Ziv B. Ari5, Yue Zhao6, Deborah Brown7, Mark DiNubile6, Michael Robertson6, Janice Wahl7, Eliav Barr6, Joan Butterton6

1Goethe University Hospital, Frankfurt, Germany, 2Texas Clinical Research Institute, Dallas, 3University of Pennsylvania, Philadelphia, 4Scripps Translational Science Institute, La Jolla, United States, 5Sheba Medical Center, Ramat Gan, Israel, 6Merck, 7Meck, Whitehouse Station, United States

Background and Aims: Safe, efficacious, and convenient antiviral regimens without interferon or ribavirin are being developed for chronic HCV infection. The C-EDGE TN study (P060) investigated the safety and efficacy of a once daily regimen of GZR (NS3/4A protease inhibitor) and EBR (NS5A inhibitor) for 12 weeks (wks) in TN patients (pts) with GT 1, 4, or 6 infection.

Methods: C-EDGE TN is an international, randomized, blinded, placebo-controlled, parallel-group trial of an oral fixed-dosed combination of GZR 100 mg/EBR 50 mg once daily in TN, HCV GT 1-, 4-, or 6-infected pts. Cirrhotic patients were eligible. Exclusion criteria included decompensated liver disease, HCC, HIV or HBV co-infection, platelets <50 x 103/ μL, or albumin <3.0 g/dL. Pts were assigned in a 3:1 ratio to receive either immediate or deferred therapy after stratification by GT and fibrosis stage assessed by biopsy or noninvasive means. HCV RNA levels were measured by the COBAS TaqMan v2.0 assay. The primary efficacy endpoint was prespecified as the proportion of treated pts in the immediate GZR/EBR arm with unquantifiable RNA levels (<15 IU/mL) 12 wks after the end of study treatment (SVR12).

Results: Overall, 421 (90%) of 469 screened pts were enrolled, randomized, and treated with ?1 dose of study drug: 194 (46%) women; 157 (37%) non-white; 385 (91%) GT1 and 36 (9%) GT4/6 infections. Among the 92 (22%) pts with cirrhosis, the diagnosis was biopsy-proven in 26 (28%); the median platelet count [IQR] and albumin level [IQR] in cirrhotics were 123.5 [91.5-157.5] x 103/μL and 4.1 [3.8-4.4] gm/dL, respectively. All pts have reached follow-up (F/U) Wk4. Based on preliminary results from 315 GZR/EBR recipients in the immediate treatment arm, 306 (97%) achieved SVR4. Virologic failure occurred in 5/315 (1.6%) pts: 1 GT1a breakthrough at treatment Wk8 and 4 relapses (2 GT1a, 2 GT6) by F/U Wk4. There were 4 (1.3%) additional pts not achieving SVR4: 2 drug-unrelated deaths (incarcerated hiatal hernia and cardiac arrhythmia), 1 drug-related AE (palpitations/anxiety with drug discontinuation on treatment Day 4), and 1 loss to F/U. Serious AEs occurred in 10 (3.2%) and 3 (2.9%) pts in the active (immediate treatment) and placebo (deferred treatment) arms, respectively.

Conclusions: Early results suggest GZR/EBR for 12 wks is efficacious and well tolerated in TN pts with GT 1, 4, or 6 infection, including pts with compensated cirrhosis. SVR12 rates and full safety data will be presented.

Disclosure of Interest: S. Zeuzem: Consultant: AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck, Sponsored Lectures (National or International): AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck, Other: Investigator for Merck, R. Ghalib: Other: Investigator for Merck, K. Reddy: Consultant: Merck, Bristol-Myers Squibb, AbbVie, Janssen, and Gilead, Other: Research support: Merck, Bristol-Myers Squibb, AbbVie, Janssen, and Gilead, Other: Investigator for Merck, P. Pockros: Grant: Gilead, AbbVie, Bristol-Myers Squibb, Janssen, and Merck, Other: Consulting fees: Gilead, AbbVie, Bristol-Myers Squibb, Janssen, and Merck, Other: Honorarium: Gilead, AbbVie, Bristol-Myers Squibb, Janssen, and Merck, Other: Investigator for Merck, Z. Ari: Other: Honorarium: Gilead, AbbVie, Bristol-Myers Squibb, Janssen, and Merck, Other: Investigator for Merck, Other: Consulting fees: Gilead, AbbVie, Bristol-Myers Squibb, Janssen, and Merck, Y. Zhao: Employee: employee of Merck, and own stock and/or stock options in the company. Other: Investigator for merck, D. Brown: Employee: employee of Merck, and own stock and/or stock options in the company. Other: Investigator for Merck, M. DiNubile: Employee: employee of Merck, and own stock and/or stock options in the company. Other: Investigator for Merck, M. Robertson: Employee: employee of Merck, and own stock and/or stock options in the company. Other: Investigator for Merck, J. Wahl: Employee: employee of Merck, and own stock and/or stock options in the company. Other: Investigator for Merck, E. Barr: Employee: employee of Merck, and own stock and/or stock options in the company. Other: Investigator for Merck, J. Butterton: Employee: employee of Merck, and own stock and/or stock options in the company. Other: Investigator for Merck

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