title: All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Florida, Gainesville, FL.
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.forename: James N
authors.initials: JN
authors.lastname: Cooper
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Lalezari
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Pockros
authors.forename: Norman
authors.initials: N
authors.lastname: Gitlin
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Freilich
authors.forename: Ziad H
authors.initials: ZH
authors.lastname: Younes
authors.forename: William
authors.initials: W
authors.lastname: Harlan
authors.forename: Reem
authors.initials: R
authors.lastname: Ghalib
authors.forename: Godson
authors.initials: G
authors.lastname: Oguchi
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thuluvath
authors.forename: Grisell
authors.initials: G
authors.lastname: Ortiz-Lasanta
authors.forename: Mordechai
authors.initials: M
authors.lastname: Rabinovitz
authors.forename: David
authors.initials: D
authors.lastname: Bernstein
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.forename: Trevor
authors.initials: T
authors.lastname: Hawkins
authors.forename: Natarajan
authors.initials: N
authors.lastname: Ravendhran
authors.forename: Aasim M
authors.initials: AM
authors.lastname: Sheikh
authors.forename: Peter
authors.initials: P
authors.lastname: Varunok
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.forename: Delphine
authors.initials: D
authors.lastname: Hennicken
authors.forename: Fiona
authors.initials: F
authors.lastname: McPhee
authors.forename: Khurram
authors.initials: K
authors.lastname: Rana
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hughes
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D000069474:Sofosbuvir; D013997:Time Factors; D014542:Uridine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014633:Valine / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D014542:Uridine Monophosphate; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir