Boceprevir: A Protease Inhibitor for the Treatment of Chronic Hepatitis C

@article{Foote2011BoceprevirAP,
  title={Boceprevir: A Protease Inhibitor for the Treatment of Chronic Hepatitis C},
  author={Bryce S. Foote and Linda M. Spooner and Paul Belliveau},
  journal={Annals of Pharmacotherapy},
  year={2011},
  volume={45},
  pages={1085 - 1093}
}
Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of boceprevir, a novel oral hepatitis C virus (HCV) nonstructural 3 (NS3) protease inhibitor for the treatment of chronic HCV infection, specifically, genotype 1. Data Sources: A literature search was conducted through MEDLINE and EMBASE (1966-May 2011) using the terms boceprevir and SCH 503034. Data from the package insert, abstracts obtained from conferences, and unpublished Phase 2-3 clinical trials, obtained… 

Tables from this paper

New Drug Review Boceprevir: A Protease Inhibitor for the Treatment of Hepatitis C

TLDR
Boceprevir was well tolerated in clinical trials and a welcomed addition to the HCV armamentarium.

Effect on Hepatitis C Virus Replication of Combinations of Direct-Acting Antivirals, Including NS5A Inhibitor Daclatasvir

TLDR
These studies demonstrated the additive-synergistic effects on replicon inhibition and clearance of combining NS3 protease or NS5B RNA polymerase inhibitors with the first-in-class, NS5A replication complex inhibitor daclatasvir (DCV), indicating that, in combination, HCV inhibitors can exert cross-target influences on resistance development.

New treatments for chronic hepatitis C: an overview for paediatricians.

TLDR
New drug regimens targeted and suitable for children would be possible in the next future if the right combination of drugs with the highest potency, barrier to resistance and the best safety profile are identified.

Retreatment of Hepatitis C Infection With Direct-Acting Antivirals.

TLDR
Veterans retreated with DAAs for HCV infection had a high success rate, and Repeat failures of DAAs were rare, but cirrhosis seems to be common among these patients.

HCV infection: an enigma, recent advances and new paradigms for its treatment

TLDR
The approval of direct-acting antivirals represents a major breakthrough for the improvement of treatment strategies against chronic HCV infection and the development of more effective, safe and well-tolerated interferon therapy is opening a new era in HCV therapeutics.

Current and emerging antiviral treatments for hepatitis C infection

TLDR
This review highlights the main therapeutic agents used in current standard of care, including telaprevir and boceprevir and projects into the not too distant future to consider treatment strategies involving combinations of agents and interferon‐free therapies, and in which patients they might prove most successful.

In Vitro Assessment of Drug-Drug Interaction Potential of Boceprevir Associated with Drug Metabolizing Enzymes and Transporters

TLDR
Overall, the data suggest that BOC has the potential to cause pharmacokinetic interactions via inhibition of CYP3A and CYP 3A/OATP1B interplay, with the interaction magnitude lower than those observed with known potent inhibitors.

Efficacy and safety of telaprevir and boceprevir in patients with hepatitis C genotype 1: a meta‐analysis

TLDR
This study compared the efficacy and safety of triple therapies including either PI to dual therapy in patients with chronic hepatitis C genotype 1 and conducted subgroup analyses to make comparisons based on patients' race.

Pharmacokinetics and Pharmacodynamics of Antiviral Drugs in Special Population

TLDR
This chapter provides a detail review of pharmacokinetic and pharmacodynamic parameters of antiviral agents utilized to treat select viral infections in patients undergoing transplantation.

References

SHOWING 1-10 OF 33 REFERENCES

Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus–infected patients

TLDR
During boceprevir monotherapy, resistance mutations at six positions within the NS3 protease were detected by way of clonal sequence analysis and impaired replicative fitness for all single mutations was revealed, whereas for combined mutations a relative increase of replication efficiency was suggested.

Boceprevir for previously treated chronic HCV genotype 1 infection.

TLDR
The addition of boceprevir to peginterferon-ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with pegintersfer on-off therapy alone.

Boceprevir for Untreated Chronic HCV Genotype 1 Infection

TLDR
The addition of boceprevir to standard therapy with peginterferon–ribavirin, as com pared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection.

SCH 503034, a novel hepatitis C virus protease inhibitor, plus pegylated interferon alpha-2b for genotype 1 nonresponders.

TLDR
Combination therapy with SCH 503034 and PEG-IFN-alpha-2b was well tolerated, with no clinically significant changes in safety parameters, and preliminary results of antiviral activity of the combination suggest a potential new therapeutic option for this hard-to-treat, nonresponder patient population.

Characterization of Human Liver Enzymes Involved in the Biotransformation of Boceprevir, a Hepatitis C Virus Protease Inhibitor

TLDR
CYP3A4 and CYP3A5 are primarily responsible for the Formation of oxidative metabolites and the formation of M28 and M31, the keto-reduced metabolites, are most likely mediated by AKR1C2 and AKR 1C3.

SCH 503034, a Mechanism-Based Inhibitor of Hepatitis C Virus NS3 Protease, Suppresses Polyprotein Maturation and Enhances the Antiviral Activity of Alpha Interferon in Replicon Cells

TLDR
A ketoamide inhibitor, SCH 503034, was generated which demonstrated potent (overall inhibition constant, 14 nM) time-dependent inhibition of the NS3 protease in cell-free enzyme assays as well as robust in vitro activity in the HCV replicon system, as monitored by immunofluorescence and real-time PCR analysis.

Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C.

TLDR
HCV-1-infected patients who can be maintained on >80% of their interferon or peginterferon alpha-2b and ribavirin dosage for the duration of treatment in the setting of a clinical trial exhibit enhanced sustained response rates.

Telaprevir and peginterferon with or without ribavirin for chronic HCV infection.

TLDR
In this phase 2 study of patients infected with HCV genotype 1 who had not been treated previously, one of the three telaprevir groups had a significantly higher rate of sustained virologic response than that with standard therapy.