Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection

Nezam Afdhal, K. Rajender Reddy, David R. Nelson, Eric Lawitz, Stuart C. Gordon, Eugene Schiff, Ronald Nahass, Reem Ghalib, Norman Gitlin, Robert Herring, Jacob Lalezari, Ziad H. Younes, Paul J. Pockros, Adrian M. Di Bisceglie, Sanjeev Arora, G. Mani Subramanian, Yanni Zhu, Hadas Dvory-Sobol, Jenny C. Yang, Phillip S. Pang & 5 others William T. Symonds, John G. McHutchison, Andrew J. Muir, Mark Sulkowski, Paul Kwo

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need. METHODS: We conducted a phase 3, randomized, open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin, with or without a protease inhibitor. Patients were randomly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily, fixed-dose combination tablet 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: Among the 440 patients who underwent randomization and were treated, 20% had cirrhosis and 79% had HCV genotype 1a infection. The rates of sustained virologic response were high in all treatment groups: 94% (95% confidence interval [CI], 87 to 97) in the group that received 12 weeks of ledipasvir-sofosbuvir; 96% (95% CI, 91 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir and ribavirin; 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir and ribavirin. No patient discontinued treatment owing to an adverse event. The most common adverse events were fatigue, headache, and nausea. CONCLUSIONS: Treatment with a once-daily, single-tablet regimen of ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment.

Original languageEnglish (US)
Pages (from-to)1483-1493
Number of pages11
JournalNew England Journal of Medicine
Volume370
Issue number16
DOIs
StatePublished - 2014

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Hepacivirus
Genotype
Ribavirin
Infection
Confidence Intervals
Therapeutics
Interferons
Tablets
sofosbuvir drug combination ledipasvir
Random Allocation
Protease Inhibitors
Nausea
Fatigue
Headache
Sustained Virologic Response
Fibrosis
Nucleotides

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Afdhal, N., Reddy, K. R., Nelson, D. R., Lawitz, E., Gordon, S. C., Schiff, E., ... Kwo, P. (2014). Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. New England Journal of Medicine, 370(16), 1483-1493. https://doi.org/10.1056/NEJMoa1316366

Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. / Afdhal, Nezam; Reddy, K. Rajender; Nelson, David R.; Lawitz, Eric; Gordon, Stuart C.; Schiff, Eugene; Nahass, Ronald; Ghalib, Reem; Gitlin, Norman; Herring, Robert; Lalezari, Jacob; Younes, Ziad H.; Pockros, Paul J.; Di Bisceglie, Adrian M.; Arora, Sanjeev; Subramanian, G. Mani; Zhu, Yanni; Dvory-Sobol, Hadas; Yang, Jenny C.; Pang, Phillip S.; Symonds, William T.; McHutchison, John G.; Muir, Andrew J.; Sulkowski, Mark; Kwo, Paul.

In: New England Journal of Medicine, Vol. 370, No. 16, 2014, p. 1483-1493.

Research output: Contribution to journalArticle

Afdhal, N, Reddy, KR, Nelson, DR, Lawitz, E, Gordon, SC, Schiff, E, Nahass, R, Ghalib, R, Gitlin, N, Herring, R, Lalezari, J, Younes, ZH, Pockros, PJ, Di Bisceglie, AM, Arora, S, Subramanian, GM, Zhu, Y, Dvory-Sobol, H, Yang, JC, Pang, PS, Symonds, WT, McHutchison, JG, Muir, AJ, Sulkowski, M & Kwo, P 2014, 'Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection', New England Journal of Medicine, vol. 370, no. 16, pp. 1483-1493. https://doi.org/10.1056/NEJMoa1316366
Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. New England Journal of Medicine. 2014;370(16):1483-1493. https://doi.org/10.1056/NEJMoa1316366
Afdhal, Nezam ; Reddy, K. Rajender ; Nelson, David R. ; Lawitz, Eric ; Gordon, Stuart C. ; Schiff, Eugene ; Nahass, Ronald ; Ghalib, Reem ; Gitlin, Norman ; Herring, Robert ; Lalezari, Jacob ; Younes, Ziad H. ; Pockros, Paul J. ; Di Bisceglie, Adrian M. ; Arora, Sanjeev ; Subramanian, G. Mani ; Zhu, Yanni ; Dvory-Sobol, Hadas ; Yang, Jenny C. ; Pang, Phillip S. ; Symonds, William T. ; McHutchison, John G. ; Muir, Andrew J. ; Sulkowski, Mark ; Kwo, Paul. / Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. In: New England Journal of Medicine. 2014 ; Vol. 370, No. 16. pp. 1483-1493.
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abstract = "BACKGROUND: Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need. METHODS: We conducted a phase 3, randomized, open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin, with or without a protease inhibitor. Patients were randomly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily, fixed-dose combination tablet 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: Among the 440 patients who underwent randomization and were treated, 20{\%} had cirrhosis and 79{\%} had HCV genotype 1a infection. The rates of sustained virologic response were high in all treatment groups: 94{\%} (95{\%} confidence interval [CI], 87 to 97) in the group that received 12 weeks of ledipasvir-sofosbuvir; 96{\%} (95{\%} CI, 91 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir and ribavirin; 99{\%} (95{\%} CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99{\%} (95{\%} CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir and ribavirin. No patient discontinued treatment owing to an adverse event. The most common adverse events were fatigue, headache, and nausea. CONCLUSIONS: Treatment with a once-daily, single-tablet regimen of ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment.",
author = "Nezam Afdhal and Reddy, {K. Rajender} and Nelson, {David R.} and Eric Lawitz and Gordon, {Stuart C.} and Eugene Schiff and Ronald Nahass and Reem Ghalib and Norman Gitlin and Robert Herring and Jacob Lalezari and Younes, {Ziad H.} and Pockros, {Paul J.} and {Di Bisceglie}, {Adrian M.} and Sanjeev Arora and Subramanian, {G. Mani} and Yanni Zhu and Hadas Dvory-Sobol and Yang, {Jenny C.} and Pang, {Phillip S.} and Symonds, {William T.} and McHutchison, {John G.} and Muir, {Andrew J.} and Mark Sulkowski and Paul Kwo",
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TY - JOUR

T1 - Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection

AU - Afdhal, Nezam

AU - Reddy, K. Rajender

AU - Nelson, David R.

AU - Lawitz, Eric

AU - Gordon, Stuart C.

AU - Schiff, Eugene

AU - Nahass, Ronald

AU - Ghalib, Reem

AU - Gitlin, Norman

AU - Herring, Robert

AU - Lalezari, Jacob

AU - Younes, Ziad H.

AU - Pockros, Paul J.

AU - Di Bisceglie, Adrian M.

AU - Arora, Sanjeev

AU - Subramanian, G. Mani

AU - Zhu, Yanni

AU - Dvory-Sobol, Hadas

AU - Yang, Jenny C.

AU - Pang, Phillip S.

AU - Symonds, William T.

AU - McHutchison, John G.

AU - Muir, Andrew J.

AU - Sulkowski, Mark

AU - Kwo, Paul

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need. METHODS: We conducted a phase 3, randomized, open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin, with or without a protease inhibitor. Patients were randomly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily, fixed-dose combination tablet 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: Among the 440 patients who underwent randomization and were treated, 20% had cirrhosis and 79% had HCV genotype 1a infection. The rates of sustained virologic response were high in all treatment groups: 94% (95% confidence interval [CI], 87 to 97) in the group that received 12 weeks of ledipasvir-sofosbuvir; 96% (95% CI, 91 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir and ribavirin; 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir and ribavirin. No patient discontinued treatment owing to an adverse event. The most common adverse events were fatigue, headache, and nausea. CONCLUSIONS: Treatment with a once-daily, single-tablet regimen of ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment.

AB - BACKGROUND: Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need. METHODS: We conducted a phase 3, randomized, open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin, with or without a protease inhibitor. Patients were randomly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily, fixed-dose combination tablet 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: Among the 440 patients who underwent randomization and were treated, 20% had cirrhosis and 79% had HCV genotype 1a infection. The rates of sustained virologic response were high in all treatment groups: 94% (95% confidence interval [CI], 87 to 97) in the group that received 12 weeks of ledipasvir-sofosbuvir; 96% (95% CI, 91 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir and ribavirin; 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir and ribavirin. No patient discontinued treatment owing to an adverse event. The most common adverse events were fatigue, headache, and nausea. CONCLUSIONS: Treatment with a once-daily, single-tablet regimen of ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment.

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DO - 10.1056/NEJMoa1316366

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