Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naive patients with chronic HCV genotype 1 infection (ESSENTIAL II)

BackgroundAlisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. AimTo evaluate efficacy and safety of ALV plus peginterferon-2a and ribavirin (PR) in treatment-naive patients with chronic HCV genotype 1 infection. MethodsDouble-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600mg once daily [response-guided therapy (RGT) for 24 or 48weeks or 48weeks fixed duration] or ALV 400mg 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 12weeks and 20% had received 24weeks of ALV/PR triple therapy. ResultsA 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 400mg twice daily and PR for >24weeks. 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. ConclusionsAlisporivir, especially the 400mg twice daily regimen, increased efficacy of PR therapy in treatment-naive patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens.