Hughes – Employment: Bristol-Myers Squibb Stephanie Noviello – Consulting: Merck/Schering-Plough; Employment: Bristol-Myers Squibb, Merck/Schering-Plough; Stock Shareholder: Merck/Scher-ing-Plough, J&J The following people have nothing to disclose: Joji Toyota, Wayne Ghesquiere, Guido

Gerken, Cheng-Yuan Peng, Ruben Terg, Marcelo O. Silva, Zhaohui Liu Background: The IFN-free, all oral combination of the protease inhibitor FDV 120 mg QD, the non-nucleoside polymerase inhibitor DBV 600 mg BID, and weight-based RBV was evaluated in HCV GT-1b infected treatment-na’ve patients including those ineligible for PegIFN. Methods: Non-cirrhotic patients, eligible/ineligible for PegIFN, were randomized to 16 weeks (w) (Arm 1; N=213) or 24w (Arm 2; N=211) of FDV+DBV+RBV. Placebo was used from 0–8w in Arm 1. Patients with compensated cirrhosis received open-label FDV+DBV+RBV for 24w (Arm 3; N=72). Primary endpoints: Selleck ZD1839 SVR12 with 16 vs 24w regimens HIF inhibitor (Arm 1 vs 2); and comparison with historical SVR rate of 68% (available DAAs at study start; SVR12 rates were adjusted by proportions of

cirrhotic patients in comparable trials and assumed response in PegIFN-ineligible patients in each arm). Results: Among 496 treated patients (male 49%, white 93%, IL28B CC 25%, F3 15% [Arms 1 and 2]), 13% were PegIFN ineligible. Comparable proportions of patients in Arms 1 (16w) and 2 (24w) achieved SVR12 ( Table, 76% vs 82%, difference estimate 6.4, 95%CI −1.4–14.2, p=0.0532); SVR12 was 74% in Arm 3. Adjusted response rates were 76% after 16w (95%CI 71–81, p=0.002 vs historical control) and 81% after 24w (95%CI 76–86, p<0.0001 vs historical control). SVR12 rates were similar in patients eligible/ineligible for PegIFN. On-treatment virologic failure occurred in 16 (8%), 17 (8%), and 9 (13%) patients and relapse occurred in 18/174 (10%), 3/169 (2%), and 6/56 (11%) patients in Arms 1, 2, and 3, respectively. Rash (27%) and photosensitivity (19%) were mostly mild. Nausea (11%) was the only adverse event (AE) of at least moderate intensity

to occur in >10% of patients ID-8 in any arm. Severe/life-threatening AEs were reported in 13% of all patients. Overall, AEs were similar for Arms 1 and 2. AEs led to discontinuation of all medication in 6% of all patients. Grade 3/4 bilirubin elevations (mostly unconjugated) were observed in 48% of all patients. Conclusions: In treatment-na’ve, non-cirrhotic patients with HCV GT-1b infection, FDV+DBV+RBV for 16 or 24w resulted in comparable SVR12 rates (76% vs 82%), with similar tolerability profiles. Patients with cirrhosis achieved SVR12 of 74% (24w). The adjusted SVR12 rates for 16 or 24w in patients with or without cirrhosis were significantly higher than historical control. Summary of efficacy (FDV+DBV+RBV; ITT) C, patients with cirrhosis.