Daclatasvir with sofosbuvir and ribavirin for hepatitis C virus infection with advanced cirrhosis or post-liver transplantation recurrence

Fred Poordad, Eugene R. Schiff, John M. Vierling, Charles Landis, Robert J. Fontana, Rong Yang, Fiona Mcphee, Eric A. Hughes, Stephanie Noviello, Eugene S. Swenson

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278 Scopus citations

Abstract

Chronic hepatitis C virus (HCV) infection with advanced cirrhosis or post-liver transplantation recurrence represents a high unmet medical need with no approved therapies effective across all HCV genotypes. The open-label ALLY-1 study assessed the safety and efficacy of a 60-mg once-daily dosage of daclatasvir (pan-genotypic NS5A inhibitor) in combination with sofosbuvir at 400 mg once daily (NS5B inhibitor) and ribavirin at 600 mg/day for 12 weeks with a 24-week follow-up in two cohorts of patients with chronic HCV infection of any genotype and either compensated/decompensated cirrhosis or posttransplantation recurrence. Patients with on-treatment transplantation were eligible to receive 12 additional weeks of treatment immediately after transplantation. The primary efficacy measure was sustained virologic response at posttreatment week 12 (SVR12) in patients with a genotype 1 infection in each cohort. Sixty patients with advanced cirrhosis and 53 with posttransplantation recurrence were enrolled; HCV genotypes 1 (76%), 2, 3, 4, and 6 were represented. Child-Pugh classifications in the advanced cirrhosis cohort were 20% A, 53% B, and 27% C. In patients with cirrhosis, 82% (95% confidence interval [CI], 67.9%-92.0%) with genotype 1 infection achieved SVR12, whereas the corresponding rates in those with genotypes 2, 3, and 4 were 80%, 83%, and 100%, respectively; SVR12 rates were higher in patients with Child-Pugh class A or B, 93%, versus class C, 56%. In transplant recipients, SVR12 was achieved by 95% (95% CI, 83.5%-99.4%) and 91% of patients with genotype 1 and 3 infection, respectively. Three patients received peritransplantation treatment with minimal dose interruption and achieved SVR12. There were no treatment-related serious adverse events. Conclusion: The pan-genotypic combination of daclatasvir, sofosbuvir, and ribavirin was safe and well tolerated. High SVR rates across multiple HCV genotypes were achieved by patients with post-liver transplantation recurrence or advanced cirrhosis.

Original languageEnglish (US)
Pages (from-to)1493-1505
Number of pages13
JournalHepatology
Volume63
Issue number5
DOIs
StatePublished - May 1 2016

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ASJC Scopus subject areas

  • Hepatology

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Poordad, F., Schiff, E. R., Vierling, J. M., Landis, C., Fontana, R. J., Yang, R., Mcphee, F., Hughes, E. A., Noviello, S., & Swenson, E. S. (2016). Daclatasvir with sofosbuvir and ribavirin for hepatitis C virus infection with advanced cirrhosis or post-liver transplantation recurrence. Hepatology, 63(5), 1493-1505. https://doi.org/10.1002/hep.28446