Abstract
Background
Boceprevir is a protease inhibitor indicated for the treatment of chronic hepatitis
C virus (HCV) genotype 1 infection in combination with peginterferon and ribavirin
for treatment-naive patients and those who previously failed to improve with interferon
and ribavirin treatment.
Objective
This article provides an overview of the mechanism of action, pharmacologic and pharmacokinetic
properties, clinical efficacy, and tolerability of boceprevir.
Methods
Relevant information was identified through a search of PubMed (1990–July 2012), EMBASE
(1990–July 2012), International Pharmaceutical Abstracts (1970–July 2012), and Google
Scholar using the key words boceprevir, SCH 503034, non-structural protein 3 (NS3) serine protease inhibitor, and direct-acting antiviral agent (DAA). Additional information was obtained from the US Food and Drug Administration's Web
site, review of the reference lists of identified articles, and posters and abstracts
from scientific meetings.
Results
Clinical efficacy of boceprevir was assessed in 2 Phase III trials, Serine Protease
Inhibitor Therapy–2 (SPRINT-2) for treatment-naive patients and Retreatment with HCV
Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 (RESPOND-2) for treatment-experienced
patients. In SPRINT-2, patients were randomized to receive peginterferon + ribavirin
(PR) or peginterferon + ribavirin + boceprevir (PRB); duration of boceprevir therapy
varied from 24, 32, to 44 weeks on the basis of HCV RNA results. The primary endpoint
was achievement of sustained virologic response (SVR; lower limit of detection, 9.3
IU/mL). The addition of boceprevir was shown to be superior, with overall SVR rates
ranging from 63% to 66% compared with 38% with PR (P < 0.001). Results of SVR in SPRINT-2 were also reorganized to monitor SVRs in black
and non-black patients. Treatment-experienced patients were assessed in RESPOND-2;
however, null responders were excluded. Patients were again randomized to PR or PRB;
duration of boceprevir therapy varied from 32 to 44 weeks on the basis of HCV RNA
results. SVR was significantly higher in patients receiving boceprevir (59%–66% vs
21% with PR; P < 0.001). This benefit was seen in both previous nonresponders (SVR, 40%–52% vs 7%
with PR), as well as previous relapsers (SVR, 69%–75% vs 29% with PR). Importantly,
SVR could be attained with a shortened course of therapy in almost one half of all
treated patients in SPRINT-2 (44%) and RESPOND-2 (46%).
Conclusions
Boceprevir was well tolerated in clinical trials and a welcomed addition to our HCV
armamentarium.
Key words
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Article info
Publication history
Published online: September 13, 2012
Accepted:
August 17,
2012
Identification
Copyright
Published by Elsevier Inc.
