Nelson – Advisory Committees or Review Panels: Merck; Grant/Research Support: Abbot, BMS, Beohringer
Ingelheim, Gilead, Genentech, Merck, Bayer, Idenix, Vertex, Jansen Leen Vijgen – Employment: Janssen Infectious Diseases BVBA Pieter Van Remoortere – Employment: Tibotec, Johnson and Johnson, Tibotec, Johnson and Johnson, Tibotec, Johnson and Johnson, Tibotec, Johnson and Johnson René Verloes – Employment: Janssen Infectious Diseases Gaston Picchio – Employment: Janssen R&D; CH5424802 Stock Shareholder: J&J Gloria Dubuc Patrick – Employment: Idenix Pharmaceuticals Maria Seifer – Employment: Idenix Pharmaceuticals, Inc. Douglas L. Mayers – Management Position: Idenix Pharmaceuticals The following people have nothing to disclose: Hillel Tobias, Joseph S. Galati, John M. Cytoskeletal Signaling inhibitor Hill Background: Daclatasvir (DCV), a potent, pangenotypic NS5A inhibitor, has been assessed in combination with other antiviral agents and/or peginterferon/ribavirin (pegIFN/RBV) in multiple phase 2 and 3 clinical studies and in various patient types. We report interim results from a long-term follow-up study (AI444-046) of patients who have completed studies of DCV-containing regimens. The objective was to assess durability of response, safety outcomes, and persistence of DCV resistance variants. Methods: This ongoing observational study follows patients,
regardless of response, for 3 years after treatment in a parent study with DCV + asunaprevir (ASV), Janus kinase (JAK) DCV + pegIFN/RBV, DCV + ASV + pegIFN/RBV, or DCV + sofos-buvir (SOF) ± RBV. Patients were enrolled within 6 months of protocol availability or completion of the parent study. At annual to semi-annual visits, patients are evaluated
for HCV RNA levels, hepatic disease progression, and drug resistance. Results: 601 eligible patients treated with DCV-based regimens were included, of whom 476 had achieved SVR12 in the parent study, including 224 and 252 patients who received pegIFN-containing and all-oral pegIFN-free regimens, respectively (Table). Patients were 52% male, 23% aged ≥65 years, 90% HCV genotype 1, and 7% cirrhotic. Overall, 471/476 (99%) patients maintained SVR12 through their most recent follow-up visit. 5 patients relapsed after achieving SVR12, 3 prior to posttreatment Week 24 in the parent study, and 2 following posttreatment Week 24 in the follow-up study. Four of the 5 relapses occurred following treatment with DCV + pegIFN/ RBV, and 1 following treatment with DCV + ASV. There were no significant changes in laboratory evaluations. Hepatic disease progression was observed in 3/601 patients, all treated with DCV + pegIFN/RBV (ascites, cirrhosis, cirrhosis + hepa-tocellular carcinoma); 2/3 did not achieve SVR in the parent study and 1/3 continues to have a durable virologic response.