Page 61 - The Flying Publisher Guide to Hepatitis C Treatment

Searching for new antiviral therapies | 61

shares an 89%, 30% and 60% homology with IFN alfa, IFN beta
and IFN omega, respectively. The CIFN molecule binds to the
IFN-alfa receptor with higher affinity than all other known IFN
alfa molecules (including the natural subtypes, the variants or
recombinants). In vitro it appears to be approximately 5 to 20-
fold more active than PegIFN alfa-2a and alfa-2b (Gonzalez 2009).
Data derived from clinical trials support the use of CIFN for
treatment-naive patients, particularly those with high VL or
genotype 1 infection (Sjogren 2005), as well as in the retreatment
of relapsers and nonresponders (Leevy 2008).
Clinical trials suggested a dose-dependent rate of viral
clearance, however the maximum tolerated dose of daily CIFN in
difficult-to-treat patients is up to 15 µg/day (Bacon 2009).
Administration of an induction dose (up to 18µg/day) or of a
higher dose (24µg/day), did not translate to better rates of SVRs
and was associated with more serious AEs and more
discontinuations (Meyer 2010).
CIFN is approved as monotherapy for CHC in adults with
compensated liver disease, and, from 2010, for retreatment of
CHC, in combination with RBV, being especially effective for
interferon-sensitive patients with lower baseline fibrosis scores.

IFN lambda (IFN-λ) is a type III interferon (comprising of
IL28A, IL28B and IL29), which has previously demonstrated
strong antiviral activity and good tolerability. IFN-λ mediates
antiviral activity through a different signaling pathway than
type I interferons (such as IFN alfa), having a complex binding
mainly through the IL28 receptor, which is present only on
plasmacytoid dendritic cells, peripheral B cell, hepatocytes and
epithelial cells. This restricted distribution compared to that of
IFN-alfa receptor offers the potential for more targeted hepatic
delivery, as well as for a better tolerability and safety profile
than the conventional interferons in terms of bone marrow
suppression (Sommereyns 2008). IFN-λ can enhance the sub-
saturating levels of IFN-ɑ and increase its antiviral efficacy. As a
result, the combination of IFNλ and IFN-ɑ may provide additive