title: Daclatasvir with sofosbuvir and ribavirin for hepatitis C virus infection with advanced cirrhosis or post-liver transplantation recurrence.
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.
  
  
  CONCLUSIONS
  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.affiliation: The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX.
authors.forename: Fred
authors.initials: F
authors.lastname: Poordad
authors.affiliation: Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Schiff
authors.affiliation: Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX.
authors.forename: John M
authors.initials: JM
authors.lastname: Vierling
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Charles
authors.initials: C
authors.lastname: Landis
authors.affiliation: University Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.affiliation: Bristol-Myers Squibb, Lawrence Township, NJ.
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.affiliation: Discovery Virology, Bristol-Myers Squibb Research and Development, Wallingford, CT.
authors.forename: Fiona
authors.initials: F
authors.lastname: McPhee
authors.affiliation: Bristol-Myers Squibb, Lawrence Township, NJ.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hughes
authors.affiliation: Bristol-Myers Squibb, Lawrence Township, NJ.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Noviello
authors.affiliation: Discovery Virology, Bristol-Myers Squibb Research and Development, Wallingford, CT.
authors.forename: Eugene S
authors.initials: ES
authors.lastname: Swenson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage*; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008103:Liver Cirrhosis / Q000209:etiology*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011759:Pyrrolidines; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D000069474:Sofosbuvir / Q000008:administration & dosage* / Q000009:adverse effects; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D012367:RNA, Viral; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir