November 4, 2013

CURRENT DESCRIPTORS: S06. HCV Therapy and Trials: New Agents (phase 2 -3)
SESSION TYPE: Plenary Session
SESSION TITLE: Presidential Plenary: Viral Hepatitis

ABSTRACT FINAL ID: Once Daily Sofosbuvir/Ledipasvir Fixed Dose Combination with or without Ribavirin Resulted in ≥95% Sustained Virologic Response In Patients with HCV Genotype 1, Including Patients with Cirrhosis: the LONESTAR trial

PRESENTER: Eric Lawitz

AUTHOR/INSTITUTIONS: E. Lawitz, F. Poordad, F.E. Membreno, The Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas, UNITED STATES|R.H. Hyland, X. Ding, C. Hebner, P.S. Pang, W.T. Symonds, J.G. McHutchison, Gilead Science, Inc, Fost

SPONSORSHIP: Gilead Sciences, Inc.

Background: In a prior phase 2 study, patients with HCV genotype 1 who received sofosbuvir (SOF), an HCV-specific uridine nucleotide analog, together with ledipasvir (LDV), an NS5A inhibitor, plus ribavirin (RBV) for 12 weeks, achieved a high rate of sustained virologic response (SVR), irrespective of whether the patients were treatment-naïve or prior null responders. We therefore assessed the safety and efficacy of 8 and 12-week regimens of a fixed-dose combination (FDC) of SOF and LDV with and without RBV in treatment-naïve and protease inhibitor-experienced patients with HCV genotype 1.

Methods: 60 non-cirrhotic treatment-naïve patients with HCV genotype 1 were randomized 1:1:1 to receive: 1) FDC for 8 weeks, 2) FDC + RBV for 8 weeks, or 3) FDC for 12 weeks. In parallel, 40 patients who had not achieved SVR after previous treatment with a protease inhibitor regimen (50% of whom also had compensated cirrhosis) were randomized to receive twelve weeks of: 1) FDC or 2) FDC + RBV. The primary end point was SVR 12 weeks after completion of treatment.

Results: 100 patients were enrolled. The treatment-naïve group was 88% genotype 1a and 20% were IL28B CC. The protease-inhibitor experienced group was 85% genotype 1a and 7.5% were IL28B CC. Biopsy-confirmed cirrhosis was present in 22/40 (55%) of the PI-experienced subjects. Results are tabulated below. SOF/LDV FDC with or without RBV for 8 and 12 weeks was generally well tolerated; 1 patient discontinued treatment early. Adverse events were generally mild, and no SAEs attributed to treatment were reported. Grade 3/4 laboratory abnormalities were infrequent. Adverse events and laboratory abnormalities consistent with the safety profile of RBV were noted in groups receiving SOF/LDV FDC+RBV. SVR12 from all groups will be presented.

Conclusions: SOF/LDV FDC elicited rapid declines in HCV RNA and high rates of SVR regardless of the presence of RBV in all treatment groups with no viral breakthrough observed. 97% of patients achieved SVR, two relapsed, and one was lost to follow up. Further evaluation of SOF/LDV FDC in treatment-naïve and treatment-experienced patients in Phase 3 studies is in progress.



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