EASL 2014 - CARE Liver Disease Faculty. Abstract O63. C-WORTHY study (HCV/HIV)

EASL 2014: Abstract O63. EFFICACY AND SAFETY OF THE ALL-ORAL REGIMEN, MK-5172/MK-8742 +/- RBV FOR 12 WEEKS IN GT1 HCV/HIV CO-INFECTED PATIENTS: THE C-WORTHY STUDY

M. Sulkowski1, J. Mallolas2, S. Pol3, M. Bourliere4, J. Gerstoft5, O. Shibolet6, R. Nahass7, E. DeJesus8, M. Shaughnessy9, P. Hwang9, J. Wahl9, M.N. Robertson9, B. Haber9

1Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Hospital Clínic, Barcelona, Spain, 3Université Paris Descartes, APHP, Unité d'Hépatologie, Hôpital Cochin, INSERM U 1016 Institut Cochin, Paris, 4Service d'Hépato-Gastroentérologie, Hôpital Saint-Joseph, Marseille, France, 5Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark, 6Department of Gastroenterology, Liver Unit, Tel Aviv Medical Center, Tel Aviv, Israel, 7ID Care, Hillsborough, NJ, 8Orlando Immunology Center, Orlando, FL, 9Merck, Whitehouse Station, NJ, United States

Background and aims: To assess the efficacy and safety of a 12 week regimen of MK-5172 (a hepatitis C virus [HCV] NS3/4A protease inhibitor) and MK-8742 (a HCV NS5A inhibitor) +/- ribavirin (RBV) in patients with genotype (GT)1 HCV and HIV co-infection. This is the first report of the treatment of co-infected patients with this all-oral, once-daily, highly potent regimen.

Results: 40 patients were enrolled (83% male, 20% African American, and 78 % GT1a). Mean baseline HCV-RNA was 6.2 log10 IU/mL. All patients that have reached treatment week 4 (n = 22) had HCV-RNA < 25 IU/mL at treatment week 4, regardless of ribavirin therapy (Table 1). The most common adverse events were: fatigue 10% (4/40); headache 5% (2/40); back pain 5% (2/40) and asthenia 5% (2/40). No patient discontinued due to either an adverse event or study medication intolerance. Enrollment is on-going; end of treatment response and follow-up week 4 data will be presented.

Conclusions: Patients with HCV GT1 infection and HIV co-infection achieved rapid viral suppression during the first 4 weeks of therapy with MK-5172 and MK-8742, regardless of ribavirin therapy.

This arm of the C-Worthy trial successfully examined 59 patients with Genotype-1 HCV/HIV co-infection who have maximally suppressed HIV on Raltegravir based ARV treatment confirming Merck’s intention to proceed with the investigation of this promising combination of all-oral, Ribavirin-free HCV treatment. Two cohorts of 29 and 30 patients received Mk-5172 (PI) + Mk-8742 (NS5A) +/- RBV respectively for 12 weeks. The majority of patients were male with G1a subtype, mean CD4 count of 625, log 6 VL and had Metavir scores of F0-2. The primary outcome was SVR12 for which interim data were presented showing that 96.6% (28/29) and 90% (26/29) achieved an SVR4. Two patients experienced on-treatment breakthrough (at TW8, with lower serum drug levels) and one patient relapsed (at FU4) all within the G1a sub-population. The treatment was well tolerated; only 1 patient experienced Hemoglobin less than 100g/dL in the RBV containing arm.

Future Phase-III studies using this regimen in a single tablet in both prior treatment experienced patients +/- cirrhosis will include patients +/- HIV co-infection as well as patients exclusively co-infected.
— CARE Liver Disease Faculty Commentary