Abstract
Background
Telaprevir is a hepatitis C NS3/4A protease inhibitor approved by the US Food and
Drug Administration as part of combination therapy for the management of chronic hepatitis
C virus (HCV) genotype 1 infection.
Objective
The article reviews published literature on telaprevir, including its chemistry, mechanism
of action, resistance, pharmacodynamic and pharmacokinetic properties, drug interactions,
therapeutic efficacy, HIV/HCV coinfection, pharmacogenomics, adverse events, pharmacoeconomics,
and dosing and administration.
Methods
English-language literature was included. Searches of MEDLINE and BIOSIS databases
from 1975 through January 2012 were performed. Emphasis was placed on reference citations
involving clinical trials, randomized controlled trials, and research in humans. Additional
publications were found by searching the reference lists of identified articles and
reviewing abstracts from recent scientific meetings. Search terms included, but were
not limited to, telaprevir, VX-950, hepatitis C virus genotype 1, resistance, pharmacology, pharmacokinetics,
pharmacodynamics, drug interactions, pharmacogenomics, adverse events, and therapeutic use.
Results
Review of the databases revealed 471 publications/abstracts on this subject. Of these,
85 were chosen based on the review criteria. Two Phase III studies investigated the
efficacy and tolerability of telaprevir administered for 12 weeks (T12) when used
with peginterferon alfa and ribavirin (PR) in treatment-naive subjects. The ADVANCE
study reported that patients who had an extended rapid virologic response (eRVR; an
undetectable HCV RNA level at both 4 and 12 weeks of treatment) with triple therapy
could be treated with PR for a total of 24 weeks (T12PR24 group) versus standard PR
treatment for 48 weeks (PR48 group [control]). The proportions of patients who achieved
sustained virologic response (SVR; undetectable HCV RNA concentration at 24 weeks
after the completion of therapy) in the T12PR24 and PR48 groups were 89% and 44%,
respectively. The ILLUMINATE study reported T12PR24 was noninferior to T12PR48 in
patients with an eRVR to combination therapy. In the REALIZE study, patients with
a history of relapse responded well to T12PR48 compared with PR48 (SVR, 83% vs 24%).
Telaprevir is a substrate/inhibitor of cytochrome P450 (CYP3A4) and a substrate/inhibitor
of P-glycoprotein and poses an important risk for drug interactions. Adverse drug
events (ADEs) reported most commonly with triple therapy compared with the T or PR
regimen alone were rash, pruritus, nausea, diarrhea, and anemia. The serious AEs most
commonly reported during T + PR therapy were anemia, rash, and pruritus. Two reports
concluded that T combined with PR was not cost-effective due to the high cost of telaprevir.
One study reported that the combination of T + PR would be cost-effective if the treatment
rate of HCV genotype 1 infected patients reached 50%.
Conclusion
Including telaprevir as part of triple therapy for the management of chronic HCV genotype
1 infection significantly increases the likelihood of achieving an SVR over standard
dual drug therapy (PR) in both treatment-naive and -experienced patients. However,
due to the high cost, the use of triple therapy with telaprevir will likely be limited
to patient groups known to respond poorly to dual therapy.
Key words
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Article info
Publication history
Published online: August 30, 2012
Accepted:
August 1,
2012
Identification
Copyright
© 2012 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
