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Fixed-dose combination therapy with daclatasvir, asunaprevir, and beclabuvir for noncirrhotic patients with HCV genotype 1 infection.

Publication ,  Journal Article
Poordad, F; Sievert, W; Mollison, L; Bennett, M; Tse, E; Bräu, N; Levin, J; Sepe, T; Lee, SS; Angus, P; Conway, B; Pol, S; Boyer, N; Tam, E ...
Published in: JAMA
May 5, 2015

IMPORTANCE: The antiviral activity of all-oral, ribavirin-free, direct-acting antiviral regimens requires evaluation in patients with chronic hepatitis C virus (HCV) infection. OBJECTIVE: To determine the rates of sustained virologic response (SVR) in patients receiving the 3-drug combination of daclatasvir (a pan-genotypic NS5A inhibitor), asunaprevir (an NS3 protease inhibitor), and beclabuvir (a nonnucleoside NS5B inhibitor). DESIGN, SETTING, AND PARTICIPANTS: This was an open-label, single-group, uncontrolled international study (UNITY-1) conducted at 66 sites in the United States, Canada, France, and Australia between December 2013 and August 2014. Patients without cirrhosis who were either treatment-naive (n = 312) or treatment-experienced (n = 103) and had chronic HCV genotype 1 infection were included. INTERVENTIONS: Patients received a twice-daily fixed-dose combination of daclatasvir, 30 mg; asunaprevir, 200 mg; and beclabuvir, 75 mg. MAIN OUTCOMES AND MEASURES: The primary study outcome was SVR12 (HCV-RNA <25 IU/mL at posttreatment week 12) in patients naive to treatment. A key secondary outcome was SVR12 in the treatment-experienced cohort. RESULTS: Baseline characteristics were comparable between the treatment-naive and treatment-experienced cohorts. Patients were 58% male, 26% had IL28B (rs12979860) CC genotype, 73% were infected with genotype 1a, and 27% were infected with genotype 1b. Overall, SVR12 was observed in 379 of 415 patients (91.3%; 95% CI, 88.6%-94.0%): 287 of 312 treatment-naive patients (92.0%; 95% CI, 89.0%-95.0%) and 92 of 103 treatment-experienced patients (89.3%; 95% CI, 83.4%-95.3%). Virologic failure occurred in 34 patients (8%) overall. One patient died at posttreatment week 3; this was not considered related to study medication. There were 7 serious adverse events, all considered unrelated to study treatment, and 3 adverse events (<1%) leading to treatment discontinuation, including 2 grade 4 alanine aminotransferase elevations. The most common adverse events (in ≥10% of patients) were headache, fatigue, diarrhea, and nausea. CONCLUSIONS AND RELEVANCE: In this open-label, nonrandomized, uncontrolled study, a high rate of SVR12 was achieved in treatment-naive and treatment-experienced noncirrhotic patients with chronic HCV genotype 1 infection who received 12 weeks of treatment with the oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01979939.

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Published In

JAMA

DOI

EISSN

1538-3598

Publication Date

May 5, 2015

Volume

313

Issue

17

Start / End Page

1728 / 1735

Location

United States

Related Subject Headings

  • Valine
  • Sulfonamides
  • Pyrrolidines
  • Middle Aged
  • Male
  • Isoquinolines
  • Indoles
  • Imidazoles
  • Humans
  • Hepatitis C, Chronic
 

Citation

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Poordad, F., Sievert, W., Mollison, L., Bennett, M., Tse, E., Bräu, N., … UNITY-1 Study Group. (2015). Fixed-dose combination therapy with daclatasvir, asunaprevir, and beclabuvir for noncirrhotic patients with HCV genotype 1 infection. JAMA, 313(17), 1728–1735. https://doi.org/10.1001/jama.2015.3860
Poordad, Fred, William Sievert, Lindsay Mollison, Michael Bennett, Edmund Tse, Norbert Bräu, James Levin, et al. “Fixed-dose combination therapy with daclatasvir, asunaprevir, and beclabuvir for noncirrhotic patients with HCV genotype 1 infection.JAMA 313, no. 17 (May 5, 2015): 1728–35. https://doi.org/10.1001/jama.2015.3860.
Poordad F, Sievert W, Mollison L, Bennett M, Tse E, Bräu N, et al. Fixed-dose combination therapy with daclatasvir, asunaprevir, and beclabuvir for noncirrhotic patients with HCV genotype 1 infection. JAMA. 2015 May 5;313(17):1728–35.
Poordad, Fred, et al. “Fixed-dose combination therapy with daclatasvir, asunaprevir, and beclabuvir for noncirrhotic patients with HCV genotype 1 infection.JAMA, vol. 313, no. 17, May 2015, pp. 1728–35. Pubmed, doi:10.1001/jama.2015.3860.
Poordad F, Sievert W, Mollison L, Bennett M, Tse E, Bräu N, Levin J, Sepe T, Lee SS, Angus P, Conway B, Pol S, Boyer N, Bronowicki J-P, Jacobson I, Muir AJ, Reddy KR, Tam E, Ortiz-Lasanta G, de Lédinghen V, Sulkowski M, Boparai N, McPhee F, Hughes E, Swenson ES, Yin PD, UNITY-1 Study Group. Fixed-dose combination therapy with daclatasvir, asunaprevir, and beclabuvir for noncirrhotic patients with HCV genotype 1 infection. JAMA. 2015 May 5;313(17):1728–1735.
Journal cover image

Published In

JAMA

DOI

EISSN

1538-3598

Publication Date

May 5, 2015

Volume

313

Issue

17

Start / End Page

1728 / 1735

Location

United States

Related Subject Headings

  • Valine
  • Sulfonamides
  • Pyrrolidines
  • Middle Aged
  • Male
  • Isoquinolines
  • Indoles
  • Imidazoles
  • Humans
  • Hepatitis C, Chronic