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.

AIM:

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: S Zeuzem, R Flisiak, J M Vierling, W Mazur, G Mazzella, S Thongsawat, D Abdurakhmanov, N Van Kính, P Calistru, J Heo, C Stanciu, M Gould, M Makara, S-J Hsu, P Buggisch, D Samuel, D Mutimer, B Nault, M Merz, W Bao, L H Griffel, C Brass, N V Naoumov, ESSENTIAL II Study Group
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 42 Issue 7 Pg. 829-44 (Oct 2015) ISSN: 1365-2036 [Electronic] England
• PMID: 26238707 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• Antiviral Agents
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• Cyclosporine
• peginterferon alfa-2a
• alisporivir

Topics

• Adolescent
• Adult
• Aged
• Antiviral Agents (administration & dosage, adverse effects)
• Cyclosporine (administration & dosage, adverse effects)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (drug effects, genetics)
• Hepatitis C, Chronic (drug therapy, virology)
• Humans
• Interferon-alpha (administration & dosage, adverse effects)
• Male
• Middle Aged
• Polyethylene Glycols (administration & dosage, adverse effects)
• Recombinant Proteins (administration & dosage, adverse effects)
• Ribavirin (administration & dosage, adverse effects)
• Treatment Outcome
• United States
• Young Adult