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

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. [ABSTRACT FROM AUTHOR]