PTH-137 Safety and efficacy of simeprevir (SMV) plus PEG-IFN/RBV in treatment-naÏve chronic hepatitis c genotype 1 patients eligible for 12 weeks of treatment
Authors: GR Foster, T Asselah, C Moreno, C Sarrazin, M Gschwantler, A Craxi, P Buggisch, R Ryan, O Lenz, G Van Dooren, I Lonjon-Domanec, M Schlag, M Buti
Journal: Gut (2015)

<h3>Introduction</h3> HPC3014 is a Phase 3, open-label study to assess if response to SMV+Peg-IFN/RBV at Week 2 can allow shortening of treatment to 12 weeks, irrespective of baseline and on-treatment factors. <h3>Method</h3> Treatment-naïve chronic HCV G1-infected patients with no-to-moderate fibrosis (METAVIR F0–F2) were recruited. In patients with HCV-RNA &lt;25 IU/mL (detectable/undetectable [Roche COBAS<sup>®</sup>Taqman<sup>® </sup>lower limit of quantification: 25 IU/mL, lower limit of detection: 15 IU/mL]) at Week 2 and undetectable at Weeks 4 and 8, all treatments were stopped at Week 12 (12-week group). If these criteria were not met, Peg-IFN/RBV was continued to Week 24 (in one case extended to Week 48). <h3>Results</h3> 123/163 (76%) patients treated were eligible for the 12-week group (53% male, 92% white, 40%G1a/60%G1b, 76% METAVIR F0/1 and 26/59/15% <i>IL28B </i>CC/CT/TT). Treatment was well tolerated in the 12-week group; all patients completed therapy and none failed on treatment; 33% (41/123) of patients relapsed and 3% (4/123) were lost to follow-up. Grade 3 AEs at least possibly related to SMV were experienced by 5% (6/123) of patients. No grade 4 AEs were considered related to SMV; 3% (4/123) of patients experienced an SAE (considered not related to SMV). AEs of special interest in &gt;10% of patients were pruritus (36%), rash (any type, 17%), neutropenia (20%), dyspnoea (15%) and anaemia (11%). Overall SVR12 in the 12-week group was 66% (81/123) but was higher in patients with <i>IL28B</i>CC genotype (94%), patients with baseline viral load ≤800,000 IU/mL (82%), those with mild fibrosis (F0–F1) (74%), and those with undetectable HCV-RNA at Week 2 (77%). Amongst patients with undetectable HCV-RNA at Week 2, SVR12 rates still varied based on baseline factors. <h3>Conclusion</h3> Week 2 response alone did not predict treatment outcomes as other baseline factors such as <i>IL28B </i>genotype, baseline viral load and fibrosis score seemed to influence SVR rates. Multivariate analyses are ongoing using factors associated with higher SVR rates shown in this analysis in order to create a strong model to select patients with a good chance of SVR after 12 weeks of therapy. <h3>Disclosure of interest</h3> G. Foster Conflict with: BMS, Gilead, Janssen, GSK, Roche, Springbank, Tekmira, T. Asselah Conflict with: AbbVie, Janssen, Gilead, BMS, Merck, Roche, C. Moreno Conflict with: AbbVie, Astellas, BMS, Gilead, Janssen, MSD, Roche, C. Sarrazin Conflict with: Abbott, Abbvie, BMS, Gilead, Janssen, Merck/MSD, Qiagen, Roche, Siemens, M. Gschwantler Conflict with: AbbVie, BMS, Gilead, Janssen, MSD, Roche, A. Craxi: None Declared, P. Buggisch Conflict with: AbbVie, BMS, Gilead, Janssen, MSD, Roche, R. Ryan Conflict with: Janssen, O. Lenz Conflict with: Janssen, G. Van Dooren Conflict with: Janssen, I. Lonjon-Domanec Conflict with: Janssen, M. Schlag Conflict with: Janssen, M. Buti Conflict with: Gilead, Janssen, MSD.