title: Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study (ALLY-3+).
abstract: Patients with hepatitis C virus (HCV) genotype 3 infection, especially those with advanced liver disease, are a challenging population in urgent need of optimally effective therapies. The combination of daclatasvir (DCV; pangenotypic nonstructural protein 5A inhibitor) and sofosbuvir (SOF; nucleotide nonstructural protein 5B inhibitor) for 12 weeks previously showed high efficacy (96%) in noncirrhotic genotype 3 infection. The phase III ALLY-3+ study (N = 50) evaluated DCV-SOF with ribavirin (RBV) in treatment-naïve (n = 13) or treatment-experienced (n = 37) genotype 3-infected patients with advanced fibrosis (n = 14) or compensated cirrhosis (n = 36). Patients were randomized 1:1 to receive open-label DCV-SOF (60 + 400 mg daily) with weight-based RBV for 12 or 16 weeks. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12). SVR12 (intention-to-treat) was 90% overall (45 of 50): 88% (21 of 24) in the 12-week (91% observed) and 92% (24 of 26) in the 16-week group. All patients with advanced fibrosis achieved SVR12. SVR12 in patients with cirrhosis was 86% overall (31 of 36): 83% (15 of 18) in the 12-week (88% observed) and 89% (16 of 18) in the 16-week group; for treatment-experienced patients with cirrhosis, these values were 87% (26 of 30), 88% (14 of 16; 93% observed), and 86% (12 of 14), respectively. One patient (12-week group) did not enter post-treatment follow-up (death unrelated to treatment). There were 4 relapses (2 per group) and no virological breakthroughs. The most common adverse events (AEs) were insomnia, fatigue, and headache. There were no discontinuations for AEs and no treatment-related serious AEs.
  
  
  CONCLUSIONS
  The all-oral regimen of DCV-SOF-RBV was well tolerated and resulted in high and similar SVR12 after 12 or 16 weeks of treatment among genotype 3-infected patients with advanced liver disease, irrespective of past HCV treatment experience.
authors.affiliation: Clinique Universitaire d'Hepato-Gastroentérologie, Pôle Digidune, CHU de Grenoble and Unité INSERM/Université Grenoble Alpes U823, IAPC Institut Albert Bonniot, Grenoble, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroy
authors.affiliation: Austin Hospital, Heidelberg, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Angus
authors.affiliation: INSERM U954, CHU de Nancy, Université de Lorraine, Nancy, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.affiliation: St. Vincent's Hospital and Kirby Institute, UNSW Australia, Sydney, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.affiliation: CHU Henri Mondor, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hezode
authors.affiliation: Monash Medical Centre, Clayton, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Pianko
authors.affiliation: Hôpital Cochin, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.affiliation: Gallipoli Medical Research Foundation, Greenslopes, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Stuart
authors.affiliation: South Australia Health, Adelaide, Australia.
authors.forename: Edmund
authors.initials: E
authors.lastname: Tse
authors.affiliation: Bristol-Myers Squibb Research & Development, Wallingford, CT.
authors.forename: Fiona
authors.initials: F
authors.lastname: McPhee
authors.affiliation: Bristol-Myers Squibb Research & Development, Princeton, NJ.
authors.forename: Rafia
authors.initials: R
authors.lastname: Bhore
authors.affiliation: Bristol-Myers Squibb Research & Development, Princeton, NJ.
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Jimenez-Exposito
authors.affiliation: St Vincent's Hospital and the University of Melbourne, Melbourne, Australia.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D002219:Carbamates; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics; 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*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; 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; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir
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