Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection

S. Zeuzem, G. R. Foster, S. Wang, A. Asatryan, E. Gane, J. J. Feld, T. Asselah, M. Bourlière, P. J. Ruane, H. Wedemeyer, S. Pol, R. Flisiak, F. Poordad, W. L. Chuang, C. A. Stedman, S. Flamm, P. Kwo, G. J. Dore, G. Sepulveda-Arzola, S. K. Roberts & 18 others R. Soto-Malave, K. Kaita, M. Puoti, J. Vierling, E. Tam, Hugo E Vargas, R. Bruck, F. Fuster, S. W. Paik, F. Felizarta, J. Kort, B. Fu, R. Liu, T. I. Ng, T. Pilot-Matias, C. W. Lin, R. Trinh, F. J. Mensa

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Abstract

BACKGROUND Glecaprevir and pibrentasvir are direct-acting antiviral agents with pangenotypic activity and a high barrier to resistance. We evaluated the efficacy and safety of 8-week and 12-week courses of treatment with 300 mg of glecaprevir plus 120 mg of pibrentasvir in patients without cirrhosis who had hepatitis C virus (HCV) genotype 1 or 3 infection. METHODS We conducted two phase 3, randomized, open-label, multicenter trials. Patients with genotype 1 infection were randomly assigned in a 1:1 ratio to receive oncedaily glecaprevir-pibrentasvir for either 8 or 12 weeks. Patients with genotype 3 infection were randomly assigned in a 2:1 ratio to receive 12 weeks of treatment with either glecaprevir-pibrentasvir or sofosbuvir-daclatasvir. Additional patients with genotype 3 infection were subsequently enrolled and nonrandomly assigned to receive 8 weeks of treatment with glecaprevir-pibrentasvir. The primary end point was the rate of sustained virologic response 12 weeks after the end of treatment. RESULTS In total, 1208 patients were treated. The rate of sustained virologic response at 12 weeks among genotype 1-infected patients was 99.1% (95% confidence interval [CI], 98 to 100) in the 8-week group and 99.7% (95% CI, 99 to 100) in the 12-week group. Genotype 3-infected patients who were treated for 12 weeks had a rate of sustained virologic response at 12 weeks of 95% (95% CI, 93 to 98; 222 of 233 patients) with glecaprevir-pibrentasvir and 97% (95% CI, 93 to 99.9; 111 of 115) with sofosbuvir-daclatasvir; 8 weeks of treatment with glecaprevir-pibrentasvir yielded a rate of 95% (95% CI, 91 to 98; 149 of 157 patients). Adverse events led to discontinuation of treatment in no more than 1% of patients in any treatment group. CONCLUSIONS Once-daily treatment with glecaprevir-pibrentasvir for either 8 weeks or 12 weeks achieved high rates of sustained virologic response among patients with HCV genotype 1 or 3 infection who did not have cirrhosis. (Funded by AbbVie; ENDURANCE-1 and ENDURANCE-3 ClinicalTrials.gov numbers, NCT02604017 and NCT02640157.)

Original languageEnglish (US)
Pages (from-to)354-369
Number of pages16
JournalNew England Journal of Medicine
Volume378
Issue number4
DOIs
StatePublished - Jan 25 2018

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Hepacivirus
Genotype
Infection
Confidence Intervals
Therapeutics
Fibrosis
Multicenter Studies
Antiviral Agents
Safety
Sustained Virologic Response

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Zeuzem, S., Foster, G. R., Wang, S., Asatryan, A., Gane, E., Feld, J. J., ... Mensa, F. J. (2018). Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. New England Journal of Medicine, 378(4), 354-369. https://doi.org/10.1056/NEJMoa1702417

Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. / Zeuzem, S.; Foster, G. R.; Wang, S.; Asatryan, A.; Gane, E.; Feld, J. J.; Asselah, T.; Bourlière, M.; Ruane, P. J.; Wedemeyer, H.; Pol, S.; Flisiak, R.; Poordad, F.; Chuang, W. L.; Stedman, C. A.; Flamm, S.; Kwo, P.; Dore, G. J.; Sepulveda-Arzola, G.; Roberts, S. K.; Soto-Malave, R.; Kaita, K.; Puoti, M.; Vierling, J.; Tam, E.; Vargas, Hugo E; Bruck, R.; Fuster, F.; Paik, S. W.; Felizarta, F.; Kort, J.; Fu, B.; Liu, R.; Ng, T. I.; Pilot-Matias, T.; Lin, C. W.; Trinh, R.; Mensa, F. J.

In: New England Journal of Medicine, Vol. 378, No. 4, 25.01.2018, p. 354-369.

Research output: Contribution to journalArticle

Zeuzem, S, Foster, GR, Wang, S, Asatryan, A, Gane, E, Feld, JJ, Asselah, T, Bourlière, M, Ruane, PJ, Wedemeyer, H, Pol, S, Flisiak, R, Poordad, F, Chuang, WL, Stedman, CA, Flamm, S, Kwo, P, Dore, GJ, Sepulveda-Arzola, G, Roberts, SK, Soto-Malave, R, Kaita, K, Puoti, M, Vierling, J, Tam, E, Vargas, HE, Bruck, R, Fuster, F, Paik, SW, Felizarta, F, Kort, J, Fu, B, Liu, R, Ng, TI, Pilot-Matias, T, Lin, CW, Trinh, R & Mensa, FJ 2018, 'Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection', New England Journal of Medicine, vol. 378, no. 4, pp. 354-369. https://doi.org/10.1056/NEJMoa1702417
Zeuzem S, Foster GR, Wang S, Asatryan A, Gane E, Feld JJ et al. Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. New England Journal of Medicine. 2018 Jan 25;378(4):354-369. https://doi.org/10.1056/NEJMoa1702417
Zeuzem, S. ; Foster, G. R. ; Wang, S. ; Asatryan, A. ; Gane, E. ; Feld, J. J. ; Asselah, T. ; Bourlière, M. ; Ruane, P. J. ; Wedemeyer, H. ; Pol, S. ; Flisiak, R. ; Poordad, F. ; Chuang, W. L. ; Stedman, C. A. ; Flamm, S. ; Kwo, P. ; Dore, G. J. ; Sepulveda-Arzola, G. ; Roberts, S. K. ; Soto-Malave, R. ; Kaita, K. ; Puoti, M. ; Vierling, J. ; Tam, E. ; Vargas, Hugo E ; Bruck, R. ; Fuster, F. ; Paik, S. W. ; Felizarta, F. ; Kort, J. ; Fu, B. ; Liu, R. ; Ng, T. I. ; Pilot-Matias, T. ; Lin, C. W. ; Trinh, R. ; Mensa, F. J. / Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. In: New England Journal of Medicine. 2018 ; Vol. 378, No. 4. pp. 354-369.
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abstract = "BACKGROUND Glecaprevir and pibrentasvir are direct-acting antiviral agents with pangenotypic activity and a high barrier to resistance. We evaluated the efficacy and safety of 8-week and 12-week courses of treatment with 300 mg of glecaprevir plus 120 mg of pibrentasvir in patients without cirrhosis who had hepatitis C virus (HCV) genotype 1 or 3 infection. METHODS We conducted two phase 3, randomized, open-label, multicenter trials. Patients with genotype 1 infection were randomly assigned in a 1:1 ratio to receive oncedaily glecaprevir-pibrentasvir for either 8 or 12 weeks. Patients with genotype 3 infection were randomly assigned in a 2:1 ratio to receive 12 weeks of treatment with either glecaprevir-pibrentasvir or sofosbuvir-daclatasvir. Additional patients with genotype 3 infection were subsequently enrolled and nonrandomly assigned to receive 8 weeks of treatment with glecaprevir-pibrentasvir. The primary end point was the rate of sustained virologic response 12 weeks after the end of treatment. RESULTS In total, 1208 patients were treated. The rate of sustained virologic response at 12 weeks among genotype 1-infected patients was 99.1{\%} (95{\%} confidence interval [CI], 98 to 100) in the 8-week group and 99.7{\%} (95{\%} CI, 99 to 100) in the 12-week group. Genotype 3-infected patients who were treated for 12 weeks had a rate of sustained virologic response at 12 weeks of 95{\%} (95{\%} CI, 93 to 98; 222 of 233 patients) with glecaprevir-pibrentasvir and 97{\%} (95{\%} CI, 93 to 99.9; 111 of 115) with sofosbuvir-daclatasvir; 8 weeks of treatment with glecaprevir-pibrentasvir yielded a rate of 95{\%} (95{\%} CI, 91 to 98; 149 of 157 patients). Adverse events led to discontinuation of treatment in no more than 1{\%} of patients in any treatment group. CONCLUSIONS Once-daily treatment with glecaprevir-pibrentasvir for either 8 weeks or 12 weeks achieved high rates of sustained virologic response among patients with HCV genotype 1 or 3 infection who did not have cirrhosis. (Funded by AbbVie; ENDURANCE-1 and ENDURANCE-3 ClinicalTrials.gov numbers, NCT02604017 and NCT02640157.)",
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TY - JOUR

T1 - Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection

AU - Zeuzem, S.

AU - Foster, G. R.

AU - Wang, S.

AU - Asatryan, A.

AU - Gane, E.

AU - Feld, J. J.

AU - Asselah, T.

AU - Bourlière, M.

AU - Ruane, P. J.

AU - Wedemeyer, H.

AU - Pol, S.

AU - Flisiak, R.

AU - Poordad, F.

AU - Chuang, W. L.

AU - Stedman, C. A.

AU - Flamm, S.

AU - Kwo, P.

AU - Dore, G. J.

AU - Sepulveda-Arzola, G.

AU - Roberts, S. K.

AU - Soto-Malave, R.

AU - Kaita, K.

AU - Puoti, M.

AU - Vierling, J.

AU - Tam, E.

AU - Vargas, Hugo E

AU - Bruck, R.

AU - Fuster, F.

AU - Paik, S. W.

AU - Felizarta, F.

AU - Kort, J.

AU - Fu, B.

AU - Liu, R.

AU - Ng, T. I.

AU - Pilot-Matias, T.

AU - Lin, C. W.

AU - Trinh, R.

AU - Mensa, F. J.

PY - 2018/1/25

Y1 - 2018/1/25

N2 - BACKGROUND Glecaprevir and pibrentasvir are direct-acting antiviral agents with pangenotypic activity and a high barrier to resistance. We evaluated the efficacy and safety of 8-week and 12-week courses of treatment with 300 mg of glecaprevir plus 120 mg of pibrentasvir in patients without cirrhosis who had hepatitis C virus (HCV) genotype 1 or 3 infection. METHODS We conducted two phase 3, randomized, open-label, multicenter trials. Patients with genotype 1 infection were randomly assigned in a 1:1 ratio to receive oncedaily glecaprevir-pibrentasvir for either 8 or 12 weeks. Patients with genotype 3 infection were randomly assigned in a 2:1 ratio to receive 12 weeks of treatment with either glecaprevir-pibrentasvir or sofosbuvir-daclatasvir. Additional patients with genotype 3 infection were subsequently enrolled and nonrandomly assigned to receive 8 weeks of treatment with glecaprevir-pibrentasvir. The primary end point was the rate of sustained virologic response 12 weeks after the end of treatment. RESULTS In total, 1208 patients were treated. The rate of sustained virologic response at 12 weeks among genotype 1-infected patients was 99.1% (95% confidence interval [CI], 98 to 100) in the 8-week group and 99.7% (95% CI, 99 to 100) in the 12-week group. Genotype 3-infected patients who were treated for 12 weeks had a rate of sustained virologic response at 12 weeks of 95% (95% CI, 93 to 98; 222 of 233 patients) with glecaprevir-pibrentasvir and 97% (95% CI, 93 to 99.9; 111 of 115) with sofosbuvir-daclatasvir; 8 weeks of treatment with glecaprevir-pibrentasvir yielded a rate of 95% (95% CI, 91 to 98; 149 of 157 patients). Adverse events led to discontinuation of treatment in no more than 1% of patients in any treatment group. CONCLUSIONS Once-daily treatment with glecaprevir-pibrentasvir for either 8 weeks or 12 weeks achieved high rates of sustained virologic response among patients with HCV genotype 1 or 3 infection who did not have cirrhosis. (Funded by AbbVie; ENDURANCE-1 and ENDURANCE-3 ClinicalTrials.gov numbers, NCT02604017 and NCT02640157.)

AB - BACKGROUND Glecaprevir and pibrentasvir are direct-acting antiviral agents with pangenotypic activity and a high barrier to resistance. We evaluated the efficacy and safety of 8-week and 12-week courses of treatment with 300 mg of glecaprevir plus 120 mg of pibrentasvir in patients without cirrhosis who had hepatitis C virus (HCV) genotype 1 or 3 infection. METHODS We conducted two phase 3, randomized, open-label, multicenter trials. Patients with genotype 1 infection were randomly assigned in a 1:1 ratio to receive oncedaily glecaprevir-pibrentasvir for either 8 or 12 weeks. Patients with genotype 3 infection were randomly assigned in a 2:1 ratio to receive 12 weeks of treatment with either glecaprevir-pibrentasvir or sofosbuvir-daclatasvir. Additional patients with genotype 3 infection were subsequently enrolled and nonrandomly assigned to receive 8 weeks of treatment with glecaprevir-pibrentasvir. The primary end point was the rate of sustained virologic response 12 weeks after the end of treatment. RESULTS In total, 1208 patients were treated. The rate of sustained virologic response at 12 weeks among genotype 1-infected patients was 99.1% (95% confidence interval [CI], 98 to 100) in the 8-week group and 99.7% (95% CI, 99 to 100) in the 12-week group. Genotype 3-infected patients who were treated for 12 weeks had a rate of sustained virologic response at 12 weeks of 95% (95% CI, 93 to 98; 222 of 233 patients) with glecaprevir-pibrentasvir and 97% (95% CI, 93 to 99.9; 111 of 115) with sofosbuvir-daclatasvir; 8 weeks of treatment with glecaprevir-pibrentasvir yielded a rate of 95% (95% CI, 91 to 98; 149 of 157 patients). Adverse events led to discontinuation of treatment in no more than 1% of patients in any treatment group. CONCLUSIONS Once-daily treatment with glecaprevir-pibrentasvir for either 8 weeks or 12 weeks achieved high rates of sustained virologic response among patients with HCV genotype 1 or 3 infection who did not have cirrhosis. (Funded by AbbVie; ENDURANCE-1 and ENDURANCE-3 ClinicalTrials.gov numbers, NCT02604017 and NCT02640157.)

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U2 - 10.1056/NEJMoa1702417

DO - 10.1056/NEJMoa1702417

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JO - New England Journal of Medicine

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SN - 1533-4406

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