Sofosbuvir + Ribavirin With or Without Peginterferon Is Well-Tolerated and Associated with High SVR Rates: Integrated Results from 4 Phase 3 Trials in HCV Genotype 1-6

Abstract

Purpose: To evaluate the efficacy and safety of sofosbuvir (SOF) combination treatment in patients chronically infected with hepatitis C virus (HCV). Methods: We conducted four phase 3 studies: 1.) NEUTRINO, in which treatment-naïve patients with genotype (GT) 1, 4, 5, and 6 infection received 12 weeks of SOF and peginterferon (PEG) and ribavirin (RBV), 2.) FISSION, in which treatment-naïve GT 2/3 patients were randomized to receive either 12 weeks of SOF+RBV or 24 weeks of PEG+RBV, 3.) POSITRON, in which interferon-ineligible, -intolerant or -unwilling GT2/3 patients were randomized to receive 12 weeks of SOF+RBV or placebo, and 4.) FUSION, in which treatment-experienced GT2/3 patients were randomized to receive 12 or 16 weeks of SOF+RBV. The primary end point in all studies was sustained virologic response (HCV RNA <25 IU/mL) 12 weeks after end of treatment (SVR12). Results: Demographics were consistent with those of the HCV-infected population in the US. Mean age was 53 (range 19, 77), mean BMI was 28 (range 17, 56), IL28B non-CC was 62%. Six percent of patients were receiving opioid replacement therapy. The proportion of patients with compensated cirrhosis at baseline was 17% in NEUTRINO, 21% in FISSION, 18% in POSITRON, and 33% in FUSION. Rates of SVR12 are shown in the table. Among GT 1 patients receiving SOF+PEG+RBV, SVR12 rate was 91%. In FISSION, POSITRON, and FUSION, patients with GT 2 infection had higher rates of SVR12 than patients with GT 3. In all four studies, patients without cirrhosis had higher rates of SVR12 than patients with cirrhosis. No genotypic and phenotypic resistance was detected in any of the patients not achieving SVR12. The most common adverse events across studies were headache, fatigue, and nausea. Rates of treatment discontinuation due to AEs were low, ranging from 0 to 2%, with SOF+RBV with or without PEG.Table: Table. Rates of SVR12 Overall and in SubgroupsConclusion: Twelve weeks of SOF combination therapy was well-tolerated and effective in the treatment of HCV GT 1-6. Previously treated patients with GT 3 infection may benefit from extending treatment to 16 weeks. Disclosure - Dr. Kowdley - Grant: Gilead, Advisory Committee: Gilead; Dr. Shiffman - Consultant: Roche, Speaker's Bureau: Gilead, Grant: Gilead & Roche; Dr. Sheikh - Grant: Gilead, Speaker's Bureau: Roche; Dr. Mangia - Advisory Committee: Gilead, Board Member: Roche; Dr. Pianko - Consultant: Gilead, Speaker's Bureau: Gilead, Grant: Gilead, Advisory Committee: Gilead; Dr. Patel - Consultant: Gilead, Speaker's Bureau: Gilead, Research Support: Gilead; Dr. Yoshida - Speaker's Bureau: Gilead & Roche, Grant: Gilead; Dr. Gordon - Grant: Gilead; Dr. Feld - Speaker's Bureau: Gilead, Grant: Gilead, Board Member: Gilead & Roche; Dr. Wyles - Grant: Gilead; Dr. Nyberg - Grant: Gilead & Roche; Dr. Younossi - Consultant: Gilead; Dr. McNally - Employee: Gilead; Dr. Brainard - Employee: Gilead; Dr. Ma - Employee: Gilead; Dr. Svarovskaia - Employee: Gilead; Dr. Symonds - Employee: Gilead; Dr. McHutchison - Employee: Gilead; Dr. Gane - Speaker's Bureau: Roche, Board Member: Gilead & Roche; Dr. Jacobson - Consultant: Gilead & Roche & Kadmon, Speaker's Bureau: Gilead & Roche, Grant: Gilead & Roche; Dr. Nelson - Grant: Gilead & Roche; Dr. Lawitz - Consultant: Gilead, Speaker's Bureau: Gilead & Kadmon, Grant: Gilead & Roche. This research was supported by an industry grant from Gilead Sciences, Inc.