Ledipasvir-sofosbuvir plus ribavirin for patients with genotype 1 HCV previously treated in clinical trials of sofosbuvir regimens

Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Viral Hepatitis

David Wyles^1,*, Paul Pockros², Giuseppe Morelli³, Ziad Younes⁴, Evguenia Svarovskaia⁵, Jenny C. Yang⁵, Phillip S. Pang⁵, Yanni Zhu⁵, John G. McHutchison⁵, Steven Flamm⁶ and Eric Lawitz⁷

DOI: 10.1002/hep.27814

© 2015 by the American Association for the Study of Liver Diseases

Publication History

Accepted manuscript online: 2 APR 2015 11:45AM EST
Manuscript Accepted: 26 MAR 2015
Manuscript Revised: 16 MAR 2015
Manuscript Received: 23 FEB 2015

Keywords: direct-acting antiviral agents; HCV NS5B polymerase inhibitor; retreatment

Abstract

Patients who fail to achieve sustained virologic response (SVR) after treatment with sofosbuvir plus ribavirin with or without peginterferon do not have established retreatment options. We conducted an open-label trial to assess the efficacy and safety of ledipasvir-sofosbuvir plus ribavirin in patients with genotype 1 HCV who did not achieve SVR after treatment in phase 2 and 3 trials of sofosbuvir regimens. We enrolled 51 patients at 24 sites in the United States. All patients received the fixed-dose combination tablet of ledipasvir-sofosbuvir once daily plus weight-based ribavirin (1000 or 1200 mg/day) for 12 weeks. The efficacy endpoint was the proportion of patients with SVR 12 weeks after discontinuation of therapy (SVR12). Of the 51 patients enrolled, 25 (49%) had previously received sofosbuvir plus peginterferon-ribavirin, 20 (39%) had received sofosbuvir-ribavirin, five (10%) had received sofosbuvir placebo plus peginterferon-ribavirin, and one (2%) received GS-0938 monotherapy. Fourteen (27%) had compensated cirrhosis at baseline, and 47 (92%) had non-CC IL28B genotypes. SVR12 was achieved by 50 of the 51 patients (98%) treated. Among the 45 patients who received sofosbuvir in prior treatment, 44 (98%) achieved SVR12. The only patient who did not achieve SVR12 was a patient with genotype 3a HCV who had been incorrectly genotyped as 1a in the previous study. Given the high rates of SVR12, no differences among patient subgroups were discernible. Of 51 patients, 41 (80%) experienced at least one adverse event, but most events were mild to moderate in severity. The most common adverse events were fatigue, headache, and diarrhea. One patient discontinued treatment due to an unrelated adverse event (bipolar disorder). Conclusion: Twelve weeks of ledipasvir-sofosbuvir plus ribavirin was an effective and safe treatment for patients who have not achieved SVR with prior regimens that included sofosbuvir. This article is protected by copyright. All rights reserved.

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