EASL 2014. CARE Liver Disease Faculty. Abstract O61. C-WORTHY study (cirrhosis)

EASL 2014: Abstract O61. EFFICACY AND SAFETY OF MK-5172 AND MK-8742 ± RIBAVIRIN IN HEPATITIS C GENOTYPE 1 INFECTED PATIENTS WITH CIRRHOSIS OR PREVIOUS NULL-REPSONSE: THE C-WORTHY STUDY

E. Lawitz1, C. Hezode2, E. Gane3, E. Tam4, M. Lagging5, L. Balart6, L. Rossaro7, R. Ghalib8, M. Shaughnessy9, P. Hwang9, J. Wahl9, M.N. Robertson9, B. Haber9

1The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, United States, 2Department of Hepatology-Gastroenterology, Henri Mondor Hospital, University of Paris-Est, Creteil, France, 3Auckland Clinical Studies, Grafton, Auckland, New Zealand, 4LAIR Centre, Vancouver, BC, Canada, 5Department of Infectious Disease, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden, 6Gastroenterology & Hepatology, Tulane University Medical Center, New Orleans, LA,7Gastroenterology and Hepatology, University of California, Davis Medical Center, Sacramento, CA, 8Texas Clinical Research Institute, Arlington, TX,9Merck, Whitehouse Station, NJ, United States

Background and aims: The aim of this study was to assess the efficacy, safety and effective treatment duration of MK-5172 (a hepatitis C virus [HCV] NS3/4A protease inhibitor) in combination with MK-8742 (an HCV NS5A replication complex inhibitor) ± ribavirin in patients with HCV genotype (GT)1 infection and poor baseline characteristics of either cirrhosis or prior null response to peginterferon / ribavirin (PEG-RBV NullR).

Results: 254 patients were enrolled (male, 58%; African American, 6%; GT1a, 65%). On-treatment response is presented according to the presence or absence of cirrhosis for patients who are either treatment-naive or PEG-RBV NullR. Overall, 59%-73% of patients had HCV-RNA < 25 IU/mL at TW2, and 94%-100% had HCV-RNA < 25 IU/mL at TW4 (Table). Adverse events reported in >10% of patients were fatigue (29%), headache (29%), and nausea (11%). The trial is on-going: end-of-treatment (EOT) and follow-up week 4 (FU4) response will be presented at the meeting.

Conclusions: MK-5172 plus MK-8742 ± RBV was associated with rapid viral suppression in the first 4 weeks of therapy, despite the treatment-resistant population profile.

This study looked at the all-oral combination of MK-5172/MK-8742 (a highly potent NS3/4A inhibitor combined with a highly potent NS5A inhibitor) in 253 difficult to treat patients. Approximately half the study population were treatment naïve (TN) individuals with compensated cirrhosis and the other half were prior PR null-responders (of which 40% had cirrhosis). The cohort arms included about 30 patients each randomized to receive the DAA’s with and without RBV for either 12 or 18 weeks. At the EASL-2014 oral presentation of these data, 90-97% of all TN cirrhotic patients achieved an undetectable VL at FU4/8. Similarly, 91-100% of PR null-responders achieved undetectable VL at FU4/8 with no benefit attributed to the addition of RBV or 18 weeks of therapy in any group. A total of 7 patients relapsed (6 G1a) and 2 patients had breakthrough (one with an NS5A resistance mutation at baseline and both with NS5A and NS3 RAVs at time of failure or follow-up). The treatment was generally very safe and well tolerated.

These results are very encouraging in that this all-oral, short, and RBV free DAA combination can achieve SVR4/8-‘cure’ rates in greater than >90% in the most difficult to treat patients (in fact, the highest cure rates published among (a RBV-sparing) treatment-experienced cirrhotic patients) prompting the ongoing phase 3 development of Mk-5172/Mk-8742 co-formulated in a single tablet in various patient populations.
— CARE Liver Disease Faculty Commentary