364 An Integrated Safety, Efficacy, and Virology Analysis of >500 Patients With Compensated Cirrhosis Treated With Ledipasvir/Sofosbuvir With or Without Ribavirin

Abstract

Background: Patients with HCV and cirrhosis represent a population in most need of treatment; however, with interferon and ribavirin (RBV)-based therapy, such patients had been more difficult to treat and cure and are often underrepresented in clinical trials. Ledipasvir/sofosbuvir (LDV/SOF) phase 2 and 3 studies included >500 patients with compensated cirrhosis. We analyzed the overall efficacy and safety, and further evaluated the impact of baseline HCV NS5A resistance associated variants (RAVs) on sustained virologic response in a population of HCV infected patients with cirrhosis. Methods: Treatment-naive or treatment-experienced patients with chronic HCV genotype 1 (GT1) infection and compensated cirrhosis who had participated in phase 2 or 3 studies and had received LDV/SOF +/RBV for 12 or 24 weeks were included in this pooled analysis. Results: Five hundred thirteen subjects with compensated cirrhosis were identified. The majority (91%) of patients had cirrhosis diagnosed by biopsy or fibroscan (>12.5 kPa). Of the 292 patients on whom a fibroscan was performed, 137/292 (47%) had a value >20 kPa. The majority were treatmentexperienced (353, 69%), male (342, 67%), GT1a (306, 60%), and IL28B non-CC (405, 79%). Two hundred forty patients (68% of the treatment- experienced patients) had previously received a protease inhibitor-containing regimen. One hundred thirteen (22%) initiated therapy with a baseline platelet count of <100,000 cells/μL. Sixty-three (12%) initiated therapy with a baseline albumin <3.5 g/dL. The patients received one of four regimens: 12 weeks of LDV/SOF (118, 23%), or LDV/SOF+RBV (204, 40%), or 24 weeks of LDV/SOF (133, 26%) or LDV/SOF+RBV (58, 11%). Overall, 96% (493/513) achieved SVR12. Among treatment-experienced patients, 12 weeks of LDV/SOF resulted in a 90% SVR rate, while adding RBV or extending treatment duration increased this rate to ≥96%. With a 1% cutoff, 94/511 (18%) cirrhotic patients were identified as having BL NS5A RAVs. SVR results by regimen and patient group and the effect of baseline NS5A RAVs on SVR will be presented. Safety in patients with cirrhosis was similar to that previously reported in patients without cirrhosis. Adverse events including anemia were more frequent in patients who received RBV. No other trends in adverse events or serious adverse events were noted. Conclusions: Based on these results, LDV/SOF is effective, safe, and well-tolerated for the treatment of HCV GT1 infection in patients with compensated cirrhosis. LDV/SOF regimens for 12 and 24 weeks were efficacious in treatment-naive cirrhotic patients with baseline HCV NS5A RAVs. High SVR rates were also achieved among treatment-experienced patients with cirrhosis when RBV was added to 12 weeks of LDV/SOF or when treatment was extended to 24 weeks.