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Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.

Publication ,  Journal Article
Afdhal, N; Zeuzem, S; Kwo, P; Chojkier, M; Gitlin, N; Puoti, M; Romero-Gomez, M; Zarski, J-P; Agarwal, K; Buggisch, P; Foster, GR; Bräu, N ...
Published in: N Engl J Med
May 15, 2014

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.).

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Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

May 15, 2014

Volume

370

Issue

20

Start / End Page

1889 / 1898

Location

United States

Related Subject Headings

  • Young Adult
  • Viral Load
  • Uridine Monophosphate
  • Sofosbuvir
  • Ribavirin
  • RNA, Viral
  • Middle Aged
  • Male
  • Humans
  • Hepatitis C, Chronic
 

Citation

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Afdhal, N., Zeuzem, S., Kwo, P., Chojkier, M., Gitlin, N., Puoti, M., … ION-1 Investigators. (2014). Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med, 370(20), 1889–1898. https://doi.org/10.1056/NEJMoa1402454
Afdhal, Nezam, Stefan Zeuzem, Paul Kwo, Mario Chojkier, Norman Gitlin, Massimo Puoti, Manuel Romero-Gomez, et al. “Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.N Engl J Med 370, no. 20 (May 15, 2014): 1889–98. https://doi.org/10.1056/NEJMoa1402454.
Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014 May 15;370(20):1889–98.
Afdhal, Nezam, et al. “Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.N Engl J Med, vol. 370, no. 20, May 2014, pp. 1889–98. Pubmed, doi:10.1056/NEJMoa1402454.
Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski J-P, Agarwal K, Buggisch P, Foster GR, Bräu N, Buti M, Jacobson IM, Subramanian GM, Ding X, Mo H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Mangia A, Marcellin P, ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014 May 15;370(20):1889–1898.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

May 15, 2014

Volume

370

Issue

20

Start / End Page

1889 / 1898

Location

United States

Related Subject Headings

  • Young Adult
  • Viral Load
  • Uridine Monophosphate
  • Sofosbuvir
  • Ribavirin
  • RNA, Viral
  • Middle Aged
  • Male
  • Humans
  • Hepatitis C, Chronic