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BROWSE SLIDES

Design

* Response-guided therapy in naive and relapsers ; W48 in non-responders

• SMV: 100 mg 1 capsule qd
• PEG-IFNα-2b: 1.5 µg/kg SC once weekly
• RBV: 600 or 1000 mg/day according to body weight
• Dosage adjustment of PEG-IFN and RBV permitted

Objective

• Primary efficacy endpoint: SVR₁₂ (undetectable HCV RNA), with 95% CI
• Safety: 70 patients sufficient to detect a 97% probability of detecting an adverse event of special interest with = 5% incidence

Baseline characteristics, and disposition

SVR₁₂ (undetectable HCV RNA IU/ml), % (95% CI), ITT

Emerging mutations in treatment failure

• Sequencing analysis of NS3: 17/18 failures (naive = 2, relapser = 1, non-responders = 14)
  • Emerging mutations: 16/17
  • Most frequent emerging mutations
    • D168V, N = 8
    • Q80R + D168E, N = 3
    • D168E, N = 2
    • R155K, N = 1
    • D168T, N = 1
    • Q80K + D168E, N = 1

Adverse events (entire treatment period)

Summary

• Treatment with SMV 100 mg qd for 12 weeks in combination with PEG IFN-a-2b + RBV (for 24 or 48 weeks) demonstrated potent antiviral activity and high rates of SVR12 in patients who were treatment-naive or had previously relapsed after IFN-based therapy, with most patients having a shorter treatment duration (24 weeks)
• Antiviral activity was also demonstrated in some patients who had failed to respond to prior IFN-based therapy
• SMV was well tolerated in all patients
  • No discontinuation of SMV for adverse event
  • Only 1 case of serious adverse event considered related to SMV (hyperbilirubinemia)
• Limitation: small sample size for the 3 populations (79 patients in total)