High Efficacy of Sofosbuvir/Velpatasvir Plus GS-9857 for 12 Weeks in Treatment-Experienced Genotype 1-6 HCV-Infected Patients, Including Those Previously Treated with Direct-Acting Antivirals: 2016 ACG Presidential Poster Award: 868

Introduction: HCV-infected patients who have been unsuccessfully treated with DAAs have limited re- treatment options. Two Phase 2 studies, GS-US-367-1168 and GS-US-367-1169, evaluated sofosbuvir/velpatasvir (SOF/VEL, 400mg/100mg) +GS-9857 (100mg) administered once daily for 12 weeks in treatment-experienced genotype (GT) 1-6 infected patients with or without cirrhosis, including those who were previously treated with DAAs. Methods: Patients with virologic failure to prior treatment with pegylated-interferon (Peg-IFN) plus RBV (GT 2-6) or any DAA (GT 2-6), NS5A-inhibitor or multiple classes of DAAs (GT1) ± Peg-IFN ± RBV regimens received open-label SOF/VEL+GS-9857 for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12) assessed by the CAP/CTM HCV 2.0 assay (LLOQ=15 IU/mL). NS5A, NS3, and NS5B regions were amplified and deep sequenced ( < 1% cutoff) at baseline and at the time of virologic failure. Results: A total of 128 patients (49% GT1, 16% GT2, 27% GT3, 5% GT4, and 2% GT6) were treated: 75% male, 82% white, 73% with non-CC IL28B allele(s), and 48% with cirrhosis. SVR12 results and the number of prior DAA-classes patients had failed prior to enrollment are shown in the Table. Overall, 27% were NS5A-experienced and 52% were non- NS5A, DAA-experienced. Baseline RAVs were detected in 60% of patients (20% NS5A; 15% NS3, 2% NS5B (no S282T). One GT3 patient with cirrhosis and NS5A RAV, Y93H, detected at baseline relapsed at post-treatment week 8. Frequently reported adverse events (AE, >10%) were headache, fatigue, diarrhea, and nausea; most were mild or moderate. No clinically significant laboratory abnormalities were observed. Conclusion: SOF/VEL + GS-9857 for 12 weeks resulted in 99% SVR12 rate in treatment-experienced patients with HCV GT 1-6. The presence of baseline RAVs had no impact on SVR. A SOF/VEL/GS-9857 fixed-dose combination for 12 weeks is being evaluated as a single-tablet regimen in DAA-experienced patients.Figure 1