104 Boceprevir (B) Combination Therapy in Null Responders (Nr): Response Dependent on Interferon Responsiveness

Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial

“…Low-dose PRB48=peginterferon alfa-2b, ribavirin 400-1000 mg, and boceprevir 800 mg three times a day for 48 weeks. 16 Data are number (%) unless otherwise indicated. PR4 (lead-in)=peginterferon alfa-2b 1·5 μg/kg plus ribavirin 800−1400 mg per day for 4 weeks.…”

“…13 Boceprevir is a novel peptidomimetic NS3 protease inhibitor that forms a covalent reversible complex with the NS3 protease in vitro and has shown potent antiviral activity in the hepatitis C virus replicon system, and in patients who previously showed no response to peginterferon administered with or without ribavirin. 14,15 In a doseascending study in null responders, 16 boceprevir, when given in combination with peginterferon alfa-2b and ribavirin, was associated with a modest incremental haemoglobin reduction, as has been recorded with other direct-acting antiviral agents in the NS3 inhibitor class. 17,18 The NS3 protease inhibitor telaprevir has also shown signifi cantly higher rates of SVR than has standard of care in patients with genotype 1 disease when given for 12 weeks in combination with regimens of peginterferon and ribavirin lasting 12, 24, or 48 weeks.…”

“…However, in our cohort, a substantial proportion of null responders during the lead-in period went on to achieve SVR with the addition of boceprevir. 16,27 In all groups, rapid virological response was highly predictive of SVR. We also recorded high rates of rapid virological response in the 48-week treatment groups.…”

Directly acting antivirals for the treatment of patients with hepatitis C infection: A clinical development update addressing key future challenges

“…In PROVE1, the discontinuation rate in the first 12 weeks with triple therapy was 18%, versus 4% with PEG-IFN and RBV. In the phase 2 studies of boceprevir, rates of anemia and ''dysgeusia" were higher with triple therapy than with standard therapy, as were discontinuation rates (26-28% vs. 14%) [20,21].…”

Long-term follow-up of patients receiving boceprevir for treatment of chronic hepatitis C

“…Patients achieving a SVR were 87 followed for durability of SVR, and patients with virologic failure 88 and RAVs emerging during boceprevir treatment were monitored 89 for longevity of RAVs and rate of return to WT virus. (Kwo et al, 2010;Poordad et al, 2011;Bacon 118 et al, 2011;Schiff et al, 2008). The SPRINT-1, SPRINT-2 and 119 RESPOND-2 studies included a lead-in treatment period with 120 peginterferon alfa-2b (1.5 lg/kg/wk) plus ribavirin (800-1400 121 mg/d) for 4 weeks prior to initiating boceprevir (800 mg three times 122 daily) in combination with PR.…”