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

Abstract

UNLABELLED:

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.

• Authors: 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
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 63 Issue 5 Pg. 1493-505 (May 2016) ISSN: 1527-3350 [Electronic] United States
• PMID: 26754432 (Publication Type: Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

Chemical References

• Antiviral Agents
• Carbamates
• Imidazoles
• Pyrrolidines
• RNA, Viral
• Ribavirin
• Valine
• daclatasvir
• Sofosbuvir

Topics

• Adult
• Aged
• Aged, 80 and over
• Antiviral Agents (administration & dosage)
• Carbamates
• Drug Therapy, Combination
• Female
• Hepatitis C, Chronic (complications, drug therapy, virology)
• Humans
• Imidazoles (administration & dosage, adverse effects)
• Liver Cirrhosis (etiology)
• Liver Transplantation (adverse effects)
• Male
• Middle Aged
• Prospective Studies
• Pyrrolidines
• RNA, Viral (blood)
• Recurrence
• Ribavirin (administration & dosage, adverse effects)
• Sofosbuvir (administration & dosage, adverse effects)
• Valine (analogs & derivatives)