title: Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II).
abstract: BACKGROUND
  Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance.
  
  
  OBJECTIVE
  To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection.
  
  
  METHODS
  Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy.
  
  
  RESULTS
  A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension.
  
  
  CONCLUSIONS
  Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens.
authors.affiliation: Frankfurt, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Bialystok, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Flisiak
authors.affiliation: Houston, TX, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Vierling
authors.affiliation: Chorzów, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Mazur
authors.affiliation: Bologna, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Mazzella
authors.affiliation: Chiang Mai, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Thongsawat
authors.affiliation: Moscow, Russia.
authors.forename: D
authors.initials: D
authors.lastname: Abdurakhmanov
authors.affiliation: Hanoi, Viet Nam.
authors.forename: N
authors.initials: N
authors.lastname: Van Kính
authors.affiliation: Bucharest, Romania.
authors.forename: P
authors.initials: P
authors.lastname: Calistru
authors.affiliation: Busan, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Heo
authors.affiliation: Iasi, Romania.
authors.forename: C
authors.initials: C
authors.lastname: Stanciu
authors.affiliation: Toronto, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Gould
authors.affiliation: Budapest, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Makara
authors.affiliation: Yunlin County, Taiwan.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Hsu
authors.affiliation: Hamburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Buggisch
authors.affiliation: Villejuif, France.
authors.forename: D
authors.initials: D
authors.lastname: Samuel
authors.affiliation: Birmingham, UK.
authors.forename: D
authors.initials: D
authors.lastname: Mutimer
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Nault
authors.affiliation: Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Merz
authors.affiliation: Novartis Pharmaceuticals, East Hanover, NJ, USA.
authors.forename: W
authors.initials: W
authors.lastname: Bao
authors.affiliation: Novartis Pharmaceuticals, East Hanover, NJ, USA.
authors.forename: L H
authors.initials: LH
authors.lastname: Griffel
authors.affiliation: Novartis Pharmaceuticals, East Hanover, NJ, USA.
authors.forename: C
authors.initials: C
authors.lastname: Brass
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: N V
authors.initials: NV
authors.lastname: Naoumov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D016572:Cyclosporine; C100416:peginterferon alfa-2a; C499715:alisporivir