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Hepatology. 2015 Apr;61(4):1127-35. doi: 10.1002/hep.27726. Epub 2015 Mar 10.

All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study.

Hepatology (Baltimore, Md.)

David R Nelson, James N Cooper, Jacob P Lalezari, Eric Lawitz, Paul J Pockros, Norman Gitlin, Bradley F Freilich, Ziad H Younes, William Harlan, Reem Ghalib, Godson Oguchi, Paul J Thuluvath, Grisell Ortiz-Lasanta, Mordechai Rabinovitz, David Bernstein, Michael Bennett, Trevor Hawkins, Natarajan Ravendhran, Aasim M Sheikh, Peter Varunok, Kris V Kowdley, Delphine Hennicken, Fiona McPhee, Khurram Rana, Eric A Hughes,

Affiliations

  1. University of Florida, Gainesville, FL.

PMID: 25614962 PMCID: PMC4409820 DOI: 10.1002/hep.27726

Abstract

UNLABELLED: Treatment options for patients with hepatitis C virus (HCV) genotype 3 infection are limited, with the currently approved all-oral regimens requiring 24-week treatment and the addition of ribavirin (RBV). This phase III study (ALLY-3; ClinicalTrials.gov: NCT02032901) evaluated the 12-week regimen of daclatasvir (DCV; pangenotypic nonstructural protein [NS]5A inhibitor) plus sofosbuvir (SOF; pangenotypic NS5B inhibitor) in patients infected with genotype 3. Patients were either treatment naïve (n = 101) or treatment experienced (n = 51) and received DCV 60 mg plus SOF 400 mg once-daily for 12 weeks. Coprimary endpoints were the proportions of treatment-naïve and treatment-experienced patients achieving a sustained virological response (SVR) at post-treatment week 12 (SVR12). SVR12 rates were 90% (91 of 101) and 86% (44 of 51) in treatment-naïve and treatment-experienced patients, respectively; no virological breakthrough was observed, and ≥99% of patients had a virological response (VR) at the end of treatment. SVR12 rates were higher in patients without cirrhosis (96%; 105 of 109) than in those with cirrhosis (63%; 20 of 32). Five of seven patients who previously failed treatment with an SOF-containing regimen and 2 of 2 who previously failed treatment with an alisporivir-containing regimen achieved SVR12. Baseline characteristics, including gender, age, HCV-RNA levels, and interleukin-28B genotype, did not impact virological outcome. DCV plus SOF was well tolerated; there were no adverse events (AEs) leading to discontinuation and only 1 serious AE on-treatment, which was unrelated to study medications. The few treatment-emergent grade 3/4 laboratory abnormalities that were observed were transient.

CONCLUSION: A 12-week regimen of DCV plus SOF achieved SVR12 in 96% of patients with genotype 3 infection without cirrhosis and was well tolerated. Additional evaluation to optimize efficacy in genotype 3-infected patients with cirrhosis is underway.

© 2015 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

References

  1. N Engl J Med. 2014 May 22;370(21):1993-2001 - PubMed
  2. J Hepatol. 2009 Oct;51(4):655-66 - PubMed
  3. J Med Virol. 2010 Oct;82(10):1647-54 - PubMed
  4. Liver Int. 2011 Jul;31 Suppl 2:1-3 - PubMed
  5. J Viral Hepat. 2011 Oct;18(10):e516-22 - PubMed
  6. Antimicrob Agents Chemother. 2013 Jan;57(1):611-3 - PubMed
  7. J Clin Virol. 2013 May;57(1):13-8 - PubMed
  8. N Engl J Med. 2013 May 16;368(20):1867-77 - PubMed
  9. N Engl J Med. 2013 May 16;368(20):1878-87 - PubMed
  10. Curr Opin Virol. 2013 Oct;3(5):514-20 - PubMed
  11. Liver Int. 2014 Feb;34 Suppl 1:18-23 - PubMed
  12. N Engl J Med. 2014 Jan 16;370(3):211-21 - PubMed
  13. JAMA Intern Med. 2014 Feb 1;174(2):204-12 - PubMed

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