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Preliminary safety findings: IFN-free DAA combination in chronic HCV patients

Safety findings from the ongoing RUBY-1 study evaluating ombitasvir / paritaprevir / ritonavir in combination with dasabuvir (3D) in chronic hepatitis C virus (HCV) genotype 1 (GT1) patients with severe renal impairment or end-stage renal disease

European Association for the Study of the Liver

April 25, 2015, Vienna, Austria: Preliminary data from an ongoing study revealed today at The International Liver Congress™ 2015 suggest that a combination of three direct-acting antivirals (DAAs) is well tolerated in patients with severe renal impairment or end-stage renal disease when used either with or without ribavirin. In addition, the combination led to rapid hepatitis C viral load suppression with no virological failures seen in the preliminary data from the ongoing open-label study.

In the study, treatment naïve non-cirrhotic adults with chronic HCV GT1 infection and chronic kidney disease (CKD) classified as stage 4 or stage 5, received 12 weeks of treatment with ombitasvir / paritaprevir / ritonavir and dasabuvir (3D) either with or without ribavirin. There was a 24-week post-treatment follow-up period. As of February 18 2015, 17 of a planned 20 patients in Cohort 1 had received treatment and six had completed treatment. The combination has been well tolerated to date, with no treatment-related serious adverse events, one hemoglobin decline to <8 g/dL, and no premature discontinuations of DAAs.

Limited data are available on the safety for treating hepatitis C infection (HCV) in patients with severe renal impairment or end-stage renal disease and many of these patients currently go untreated and are vulnerable to disease progression.

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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.

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Late Breakers: Hall D Presentation time: 18:00-18:15 Presenter: Paul Pockros (United States) Abstract LO1: SAFETY OF OMBITASVIR/PARITAPREVIR/RITONAVIR PLUS DASABUVIR FOR TREATING HCV GT1 INFECTION IN PATIENTS WITH SEVERE RENAL IMPAIRMENT OR END-STAGE RENAL DISEASE: THE RUBY-I STUDY

SAFETY OF OMBITASVIR/PARITAPREVIR/RITONAVIR PLUS DASABUVIR FOR TREATING HCV GT1 INFECTION IN PATIENTS WITH SEVERE RENAL IMPAIRMENT OR END-STAGE RENAL DISEASE: THE RUBY-I STUDY

Paul J. Pockros* 1, K R. Reddy2, Parvez S. Mantry3, Eric Cohen4, Michael Bennett5, Mark S. Sulkowski6, David Bernstein7, Thomas Podsadecki4, Daniel Cohen4, Nancy S. Shulman4, Deli Wang4, Amit Khatri4, Manal Abunimeh4, Eric Lawitz8

1Scripps Clinic, La Jolla, 2University of Pennsylvania, Philadelphia, 3The Liver Institute at Methodist Dallas, Dallas, 4AbbVie Inc., North Chicago, 5Medical Associates Research Group, San Diego, 6Johns Hopkins University, Baltimore, 7North Shore University Hospital, Manhasset, 8The Texas Liver Institute, University of Texas Health Science Center, San Antonio, United States

Corresponding author's email: laurinda.cooker@abbvie.com

Introduction: Limited data are available on the safety of direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV) infection in patients with severe renal impairment or end-stage renal disease; many go untreated and are vulnerable to disease progression. RUBY-I is an ongoing, open-label study evaluating the interferon-free 3 DAA (3D) combination of ombitasvir/paritaprevir*/ritonavir (25/150/100mg QD) and dasabuvir (250mg BID) with or without ribavirin (RBV, 200mg QD) in patients with stage 4 or 5 chronic kidney disease (CKD) and HCV genotype (GT) 1 infection. We report preliminary safety results from Cohort 1 of this study.

Material and Methods: Treatment-naïve, non-cirrhotic adults with HCV GT1 infection and CKD classified using estimated glomerular filtration rate (eGFR) as stage 4 (eGFR 15-30 mL/min/1.73m2) or stage 5 (eGFR <15 mL/min/1.73m2 or requiring dialysis) receive 12 weeks of treatment with 3D with RBV (GT1a) or without RBV (GT1b), with 24 weeks post-treatment follow-up. On-treatment adverse events (AEs), serious AEs and notable laboratory abnormalities through 18 Feb 2015 are reported.

Results: 17 (of 20 planned) patients in Cohort 1 received study drug as of 18 Feb 2015; six have completed treatment. 13 of 17 patients reported at least 1 AE, mainly mild or moderate in severity. Two patients experienced serious AEs considered unrelated to DAAs (1 patient: diskitis, respiratory failure. 1 patient: pseudoaneurysm, hemoperitoneum, small bowel obstruction). Both briefly interrupted 3D due to complications of hospitalization; no other patient had an interruption or discontinuation of 3D. Six patients met hemoglobin criteria for interruption of RBV (hemoglobin decrease >2 g/dL during any 4-wk period, or a value <10 g/dL at any time). There was one case of hemoglobin <8 g/dL (hospitalized patient with diskitis). No blood transfusions were performed. All viral loads suppressed rapidly on treatment and there are no cases of virologic rebound or relapse to date.

Conclusions: Among HCV GT1-infected patients with stage 4 or 5 CKD in this ongoing trial, the regimen of 3D±RBV has been well tolerated to date, with no treatment-related serious AEs, one hemoglobin decline to <8 g/dL, and no premature discontinuations of DAAs. All viral loads suppressed rapidly on treatment and there are no virologic failures to date. Available pharmacokinetic and SVR data will be presented.

*Paritaprevir was identified by AbbVie and Enanta.

Disclosure of Interest: P. Pockros: Grant: Conflict with: Gilead, AbbVie, Janssen, BMS, Merck, Conatus, Roche Molecular, Consultant: Conflict with: Gilead, AbbVie, Janssen, BMS, K. Reddy: Grant: Conflict with: Gilead, BMS, AbbVie, Merck, Vertex, and Janssen, Consultant: Conflict with: Gilead, BMS, AbbVie, Merck, Genentech-Roche, Vertex, and Janssen, P. Mantry: Grant: Conflict with: Abbvie, Merck, Gilead, Janssen, Salix, Onyx, Hyperion, Vital Therapies, Intercept, Mass Biologics, Santaris, Consultant: Conflict with: Abbvie, Merck, Gilead, Janssen, Salix, Onyx, Hyperion, Vital Therapies, Intercept, Mass Biologics, Santaris, E. Cohen: Stockholder: Conflict with: AbbVie, Employee: Conflict with: AbbVie, M. Bennett: Stockholder: Conflict with: AbbVie, M. Sulkowski: Grant: Conflict with: AbbVie, BMS, Gilead, Janssen, Merck, Consultant: Conflict with: AbbVie, Achillion, BMS, Gilead, Janssen, Merck, D. Bernstein: Grant: Conflict with: AbbVie, BMS, Gilead, Janssen, Merck, Genentech, Consultant: Conflict with: AbbVie, Gilead, Janssen, Merck, T. Podsadecki: Stockholder: Conflict with: AbbVie, Employee: Conflict with: AbbVie, D. Cohen: Stockholder: Conflict with: AbbVie, Employee: Conflict with: AbbVie, N. Shulman: Stockholder: Conflict with: AbbVie, Employee: Conflict with: AbbVie, D. Wang: Stockholder: Conflict with: AbbVie, Employee: Conflict with: AbbVie, A. Khatri: Stockholder: Conflict with: AbbVie, Employee: Conflict with: AbbVie, M. Abunimeh: Stockholder: Conflict with: AbbVie, Employee: Conflict with: AbbVie, E. Lawitz: Grant: Conflict with: AbbVie, Achillion, Boehringer Ingelheim, BMS, Gilead Sciences, GSK, Idenix, Intercept Pharmaceuticals, Janssen, Medtronic, Merck, Novartis, Presidio, Roche, Santaris Pharmaceuticals, Vertex, Consultant: Conflict with: AbbVie, Achillion, BioCryst, Biotica, Enanta, Idenix, Janssen, Merck, Novartis, Santaris, Theravance, Vertex, Sponsored Lectures (National and International): Conflict with: Gilead, GSK , Kadmon, Merck, Vertex

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