Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naïve genotype 1 hepatitis C: The randomized PILLAR study

摘要: The availability of direct-acting antiviral agents has recently transformed the treatment chronic hepatitis C (CHC).1,2 Triple-therapy regimens that include nonstructural protein (NS)3/4A protease inhibitors, such as boceprevir and telaprevir, combined with pegylated interferon (Peg-IFN) ribavirin (RBV) significantly improve rate sustained virologic response (SVR) for patients genotype 1 CHC infection, compared Peg-IFN RBV alone.3,4 Furthermore, many may qualify a shortened duration therapy by incorporating response-guided (RGT) algorithm determines according to on-treatment milestones.5 However, these have also increased complexity amplified adverse events (AEs) associated therapy.6,7 Strict adherence three-times-daily dosing is required along recommendations be administered food (with specific fat content telaprevir) enhance absorption medications.6 Anemia more frequent severe when either used RBV, whereas skin rash common telaprevir-containing regimens.3,4 Thus, effective treatments simplified schedules improved AE profiles would benefit CHC. Simeprevir (SMV; TMC435) an oral, once-daily (QD), investigational virus (HCV) NS3/4A macrocyclic inhibitor potent activity in infected well demonstrated against isolates genotypes 2, 4, 5, 6.8,9 In preclinical studies, replicon half-maximal concentration (EC50) SMV ranged from 8 28 nM, liver-to-plasma ratio was high (ratio 39).10 phase I study, treated 5-day course monotherapy exhibited median maximal reduction HCV RNA 3.9 log10, which compares favorably observed (~2.45 log10 over 7 days) telaprevir (~4.4 14 days).8,11,12 Manns et al. triple (dose range: 25-200 mg QD) plus Peg-IFN-α-2a IIa study up days.13 majority patients, both naive experienced, had below lower level quantification (<25 IU/mL) assay day therapy.13 The aim current assess efficacy safety two different doses QD durations combination treatment-naive 1.