Sofosbuvir for previously untreated chronic hepatitis C infection

Eric Lawitz, Alessandra Mangia, David Wyles, Maribel Rodriguez-Torres, Tarek Hassanein, Stuart C. Gordon, Michael Schultz, Mitchell N. Davis, Zeid Kayali, K. Rajender Reddy, Ira M. Jacobson, Kris V. Kowdley, Lisa Nyberg, G. Mani Subramanian, Robert H. Hyland, Sarah Arterburn, Deyuan Jiang, John McNally, Diana Brainard, William T. Symonds & 4 others John G. McHutchison, Aasim M. Sheikh, Zobair Younossi, Edward J. Gane

Research output: Contribution to journalArticle

Abstract

BACKGROUND: In phase 2 trials, the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus (HCV) genotype 1, 2, or 3 infection. METHODS: We conducted two phase 3 studies in previously untreated patients with HCV infection. In a single-group, open-label study, we administered a 12-week regimen of sofosbuvir plus peginterferon alfa-2a and ribavirin in 327 patients with HCV genotype 1, 4, 5, or 6 (of whom 98% had genotype 1 or 4). In a noninferiority trial, 499 patients with HCV genotype 2 or 3 infection were randomly assigned to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks. In the two studies, the primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: In the single-group study, a sustained virologic response was reported in 90% of patients (95% confidence interval, 87 to 93). In the noninferiority trial, a sustained response was reported in 67% of patients in both the sofosbuvir-ribavirin group and the peginterferon-ribavirin group. Response rates in the sofosbuvir-ribavirin group were lower among patients with genotype 3 infection than among those with genotype 2 infection (56% vs. 97%). Adverse events (including fatigue, headache, nausea, and neutropenia) were less common with sofosbuvir than with peginterferon. CONCLUSIONS: In a single-group study of sofosbuvir combined with peginterferon-ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks. In a noninferiority trial, patients with genotype 2 or 3 infection who received either sofosbuvir or peginterferon with ribavirin had nearly identical rates of response (67%). Adverse events were less frequent with sofosbuvir than with peginterferon. (Funded by Gilead Sciences; FISSION and NEUTRINO ClinicalTrials.gov numbers, NCT01497366 and NCT01641640, respectively.)

Original languageEnglish (US)
Pages (from-to)1878-1887
Number of pages10
JournalNew England Journal of Medicine
Volume368
Issue number20
DOIs
StatePublished - May 16 2013
Externally publishedYes

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Chronic Hepatitis C
Ribavirin
Genotype
Hepacivirus
Infection
Virus Diseases
Sofosbuvir
Neutropenia
Nausea
Fatigue
Headache
Nucleotides
Confidence Intervals

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lawitz, E., Mangia, A., Wyles, D., Rodriguez-Torres, M., Hassanein, T., Gordon, S. C., ... Gane, E. J. (2013). Sofosbuvir for previously untreated chronic hepatitis C infection. New England Journal of Medicine, 368(20), 1878-1887. https://doi.org/10.1056/NEJMoa1214853

Sofosbuvir for previously untreated chronic hepatitis C infection. / Lawitz, Eric; Mangia, Alessandra; Wyles, David; Rodriguez-Torres, Maribel; Hassanein, Tarek; Gordon, Stuart C.; Schultz, Michael; Davis, Mitchell N.; Kayali, Zeid; Reddy, K. Rajender; Jacobson, Ira M.; Kowdley, Kris V.; Nyberg, Lisa; Subramanian, G. Mani; Hyland, Robert H.; Arterburn, Sarah; Jiang, Deyuan; McNally, John; Brainard, Diana; Symonds, William T.; McHutchison, John G.; Sheikh, Aasim M.; Younossi, Zobair; Gane, Edward J.

In: New England Journal of Medicine, Vol. 368, No. 20, 16.05.2013, p. 1878-1887.

Research output: Contribution to journalArticle

Lawitz, E, Mangia, A, Wyles, D, Rodriguez-Torres, M, Hassanein, T, Gordon, SC, Schultz, M, Davis, MN, Kayali, Z, Reddy, KR, Jacobson, IM, Kowdley, KV, Nyberg, L, Subramanian, GM, Hyland, RH, Arterburn, S, Jiang, D, McNally, J, Brainard, D, Symonds, WT, McHutchison, JG, Sheikh, AM, Younossi, Z & Gane, EJ 2013, 'Sofosbuvir for previously untreated chronic hepatitis C infection', New England Journal of Medicine, vol. 368, no. 20, pp. 1878-1887. https://doi.org/10.1056/NEJMoa1214853
Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC et al. Sofosbuvir for previously untreated chronic hepatitis C infection. New England Journal of Medicine. 2013 May 16;368(20):1878-1887. https://doi.org/10.1056/NEJMoa1214853
Lawitz, Eric ; Mangia, Alessandra ; Wyles, David ; Rodriguez-Torres, Maribel ; Hassanein, Tarek ; Gordon, Stuart C. ; Schultz, Michael ; Davis, Mitchell N. ; Kayali, Zeid ; Reddy, K. Rajender ; Jacobson, Ira M. ; Kowdley, Kris V. ; Nyberg, Lisa ; Subramanian, G. Mani ; Hyland, Robert H. ; Arterburn, Sarah ; Jiang, Deyuan ; McNally, John ; Brainard, Diana ; Symonds, William T. ; McHutchison, John G. ; Sheikh, Aasim M. ; Younossi, Zobair ; Gane, Edward J. / Sofosbuvir for previously untreated chronic hepatitis C infection. In: New England Journal of Medicine. 2013 ; Vol. 368, No. 20. pp. 1878-1887.
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abstract = "BACKGROUND: In phase 2 trials, the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus (HCV) genotype 1, 2, or 3 infection. METHODS: We conducted two phase 3 studies in previously untreated patients with HCV infection. In a single-group, open-label study, we administered a 12-week regimen of sofosbuvir plus peginterferon alfa-2a and ribavirin in 327 patients with HCV genotype 1, 4, 5, or 6 (of whom 98{\%} had genotype 1 or 4). In a noninferiority trial, 499 patients with HCV genotype 2 or 3 infection were randomly assigned to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks. In the two studies, the primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: In the single-group study, a sustained virologic response was reported in 90{\%} of patients (95{\%} confidence interval, 87 to 93). In the noninferiority trial, a sustained response was reported in 67{\%} of patients in both the sofosbuvir-ribavirin group and the peginterferon-ribavirin group. Response rates in the sofosbuvir-ribavirin group were lower among patients with genotype 3 infection than among those with genotype 2 infection (56{\%} vs. 97{\%}). Adverse events (including fatigue, headache, nausea, and neutropenia) were less common with sofosbuvir than with peginterferon. CONCLUSIONS: In a single-group study of sofosbuvir combined with peginterferon-ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90{\%} at 12 weeks. In a noninferiority trial, patients with genotype 2 or 3 infection who received either sofosbuvir or peginterferon with ribavirin had nearly identical rates of response (67{\%}). Adverse events were less frequent with sofosbuvir than with peginterferon. (Funded by Gilead Sciences; FISSION and NEUTRINO ClinicalTrials.gov numbers, NCT01497366 and NCT01641640, respectively.)",
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T1 - Sofosbuvir for previously untreated chronic hepatitis C infection

AU - Lawitz, Eric

AU - Mangia, Alessandra

AU - Wyles, David

AU - Rodriguez-Torres, Maribel

AU - Hassanein, Tarek

AU - Gordon, Stuart C.

AU - Schultz, Michael

AU - Davis, Mitchell N.

AU - Kayali, Zeid

AU - Reddy, K. Rajender

AU - Jacobson, Ira M.

AU - Kowdley, Kris V.

AU - Nyberg, Lisa

AU - Subramanian, G. Mani

AU - Hyland, Robert H.

AU - Arterburn, Sarah

AU - Jiang, Deyuan

AU - McNally, John

AU - Brainard, Diana

AU - Symonds, William T.

AU - McHutchison, John G.

AU - Sheikh, Aasim M.

AU - Younossi, Zobair

AU - Gane, Edward J.

PY - 2013/5/16

Y1 - 2013/5/16

N2 - BACKGROUND: In phase 2 trials, the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus (HCV) genotype 1, 2, or 3 infection. METHODS: We conducted two phase 3 studies in previously untreated patients with HCV infection. In a single-group, open-label study, we administered a 12-week regimen of sofosbuvir plus peginterferon alfa-2a and ribavirin in 327 patients with HCV genotype 1, 4, 5, or 6 (of whom 98% had genotype 1 or 4). In a noninferiority trial, 499 patients with HCV genotype 2 or 3 infection were randomly assigned to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks. In the two studies, the primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: In the single-group study, a sustained virologic response was reported in 90% of patients (95% confidence interval, 87 to 93). In the noninferiority trial, a sustained response was reported in 67% of patients in both the sofosbuvir-ribavirin group and the peginterferon-ribavirin group. Response rates in the sofosbuvir-ribavirin group were lower among patients with genotype 3 infection than among those with genotype 2 infection (56% vs. 97%). Adverse events (including fatigue, headache, nausea, and neutropenia) were less common with sofosbuvir than with peginterferon. CONCLUSIONS: In a single-group study of sofosbuvir combined with peginterferon-ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks. In a noninferiority trial, patients with genotype 2 or 3 infection who received either sofosbuvir or peginterferon with ribavirin had nearly identical rates of response (67%). Adverse events were less frequent with sofosbuvir than with peginterferon. (Funded by Gilead Sciences; FISSION and NEUTRINO ClinicalTrials.gov numbers, NCT01497366 and NCT01641640, respectively.)

AB - BACKGROUND: In phase 2 trials, the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus (HCV) genotype 1, 2, or 3 infection. METHODS: We conducted two phase 3 studies in previously untreated patients with HCV infection. In a single-group, open-label study, we administered a 12-week regimen of sofosbuvir plus peginterferon alfa-2a and ribavirin in 327 patients with HCV genotype 1, 4, 5, or 6 (of whom 98% had genotype 1 or 4). In a noninferiority trial, 499 patients with HCV genotype 2 or 3 infection were randomly assigned to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks. In the two studies, the primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: In the single-group study, a sustained virologic response was reported in 90% of patients (95% confidence interval, 87 to 93). In the noninferiority trial, a sustained response was reported in 67% of patients in both the sofosbuvir-ribavirin group and the peginterferon-ribavirin group. Response rates in the sofosbuvir-ribavirin group were lower among patients with genotype 3 infection than among those with genotype 2 infection (56% vs. 97%). Adverse events (including fatigue, headache, nausea, and neutropenia) were less common with sofosbuvir than with peginterferon. CONCLUSIONS: In a single-group study of sofosbuvir combined with peginterferon-ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks. In a noninferiority trial, patients with genotype 2 or 3 infection who received either sofosbuvir or peginterferon with ribavirin had nearly identical rates of response (67%). Adverse events were less frequent with sofosbuvir than with peginterferon. (Funded by Gilead Sciences; FISSION and NEUTRINO ClinicalTrials.gov numbers, NCT01497366 and NCT01641640, respectively.)

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