Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection

Nezam Afdhal, Stefan Zeuzem, Paul Kwo, Mario Chojkier, Norman Gitlin, Massimo Puoti, Manuel Romero-Gomez, Jean Pierre Zarski, Kosh Agarwal, Peter Buggisch, Graham R. Foster, Norbert Bräu, Maria Buti, Ira M. Jacobson, G. Mani Subramanian, Xiao Ding, Hongmei Mo, Jenny C. Yang, Phillip S. Pang, William T. SymondsJohn G. McHutchison, Andrew J. Muir, Alessandra Mangia, Patrick Marcellin

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: In phase 2 studies, treatment with the all-oral combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir resulted in high rates of sustained virologic response among previously untreated patients with hepatitis C virus (HCV) genotype 1 infection. METHODS: We conducted a phase 3, open-label study involving previously untreated patients with chronic HCV genotype 1 infection. Patients were randomly assigned in a 1:1:1:1 ratio to receive ledipasvir and sofosbuvir in a fixed-dose combination tablet once daily for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: Of the 865 patients who underwent randomization and were treated, 16% had cirrhosis, 12% were black, and 67% had HCV genotype 1a infection. The rates of sustained virologic response were 99% (95% confidence interval [CI], 96 to 100) in the group that received 12 weeks of ledipasvir-sofosbuvir; 97% (95% CI, 94 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir plus ribavirin; 98% (95% CI, 95 to 99) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 97 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir plus ribavirin. No patient in either 12-week group discontinued ledipasvir- sofosbuvir owing to an adverse event. The most common adverse events were fatigue, headache, insomnia, and nausea. CONCLUSIONS: Once-daily ledipasvir-sofosbuvir with or without ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection. (Funded by Gilead Sciences; ION-1 ClinicalTrials.gov number NCT01701401.)

Original languageEnglish
Pages (from-to)1889-1898
Number of pages10
JournalNew England Journal of Medicine
Volume370
Issue number20
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Medicine(all)

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