EASL 2014 Abstract. LBA O165. SIMEPREVIR PLUS SOFOSBUVIR WITH/WITHOUT RIBAVIRIN IN HCV GENOTYPE 1 PRIOR NULL-RESPONDER/TREATMENT-NAÏVE PATIENTS (COSMOS STUDY): PRIMARY ENDPOINT (SVR12) RESULTS IN PATIENTS WITH METAVIR F3-4 (COHORT 2)
E. Lawitz1, R. Ghalib2, M. Rodriguez-Torres3, Z.M. Younossi4, A. Corregidor5, M.S. Sulkowski6, E. DeJesus7, B. Pearlman8, M. Rabinovitz9, N. Gitlin10, J.K. Lim11, P.J. Pockros12, B. Fevery13, T. Lambrecht14, S. Ouwerkerk-Mahadevan13, K. Callewaert13, W.T. Symonds15, G. Picchio16, K. Lindsay16, M. Beumont-Mauviel13, I.M. Jacobson17
1Texas Liver Institute, San Antonio, 2Medicine and Gastroenterology and Hepatology, The Liver Institute, Dallas, TX, 3Fundación de Investigación, San Juan, PR, 4Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, 5Borland-Groover Clinic, 4800 Belfort Rd, Jacksonville, FL, 6Johns Hopkins University School of Medicine, Baltimore, MD, 7Orlando Immunology Center, Orlando, FL, 8Atlanta Medical Center, Atlanta, GA, 9University of Pittsburgh Medical Center, Pittsburgh, PA, 10Atlanta Gastroenterology Association, Atlanta, GA, 11Yale School of Medicine, New Haven, CT, 12Scripps Clinic, La Jolla, CA, United States, 13Janssen Research & Development, Beerse, 14Novellas Healthcare, Zellik, Belgium, 15Gilead Sciences Inc, Foster City, CA, 16Janssen Research & Development LLC, Titusville, NJ, 17Weill Cornell Medical College, New York, NY, United States
Background and aims: Simeprevir (protease inhibitor;SMV) + pegylated interferon/ribavirin (PR) and sofosbuvir (polymerase inhibitor;SOF)+ PR or ribavirin (R) have recently been approved for treating hepatitis C infection. The Phase 2 COSMOS trial evaluates their use in combination +/- R. We present the primary analysis of SVR12 results in genotype (GT) 1-infected, treatment-naïve and null responders to PR with advanced fibrosis (METAVIR F3-4).
Results: 87 patients were randomized and treated: 54% null responders;47% METAVIR F4;79% IL28B genotype non-CC;78% GT1a(40% with Q80K);9.2% Black/African-American. Table: 3 patients discontinued treatment for non-virologic failure; in ITT and modified ITT analyses, overall SVR12 were 94.3% (82/87) and 96.4% (81/84), respectively; SVR12 rates were high in both patients with advanced fibrosis/cirrhosis (92.7%) and in GT1a Q80K-positive patients (96.3%). No viral breakthroughs occurred. Relapse occurred in 3 GT1a-infected patients (one with Q80K) within 8 weeks after EOT. Adverse events (AEs; 87.4%) were mostly Grade 1/2 (77.0%, most commonly: fatigue 37.9%, headache 19.5%). Four serious AEs were reported. Two patients (2/87, 2.3%) discontinued treatment due to AEs.
Conclusions: SMV+SOF±RBV for 12/24wks led to overall SVR rates >96% in a modified ITT analysis, and >90% in subgroups of HCV GT1 patients with advanced fibrosis/cirrhosis including prior null responders, and in GT1a patients with baseline Q80K polymorphism. RBV did not improve SVR in any subgroup. The SMV+SOF combination was safe and well tolerated.