Page 66 - The Flying Publisher Guide to Hepatitis C Treatment

66 | Hepatitis C Treatment

Both FDA-approved PIs – Telaprevir and Boceprevir – are
peptidomimetic PIs that bind reversibly and block the protease
catalytic site.
However, monotherapy with PIs is not an option, due to
early emergence of resistance. Minor resistant populations
preexist at baseline in all HCV-infected patients and are rapidly
selected with PIs monotherapy. Therefore, boceprevir and
telaprevir still require a platform of PegIFN/RBV. When
administered in this triple therapy combination, each of the two
PIs substantially increases the rates of SVR in both treatment-
naive and treatment-experienced patients.

Triple therapy
Triple therapy with a PI was shown to almost double the
success rate in treatment-naive patients infected with HCV
genotype 1 from 38-44% obtained with SoC to 63-75% (Poordad
2011). The increase in SVR rate is even higher in previous
nonresponders-from 17-21% with SoC to 59-66% with triple
therapy (Bacon 2011). Nevertheless, the addition of a new agent
to an existing treatment regimen will pose substantial challenges
in terms of drug interactions and adherence, due to the
associated side effects and risk of resistance emergence.
Maximizing tolerance of future PIs based regimens will be
extremely important to achieve optimal treatment outcomes.
Telaprevir (Incivek™, Vertex Pharmaceuticals) was approved
by FDA for treatment of genotype 1 CHC in adult naive patients
with compensated liver disease, including cirrhosis, and in prior
null responders, partial responders, and relapsers, only in
combination with PegIFN/RBV.
Preliminary studies have demonstrated that 14 days
monotherapy, while inducing a VL median decline of more than
4.4 log 10 units in patients with CHC G1 infection, was limited by
the appearance of resistance mutation as early as 4-7 days after
initiation. Interestingly, the mutations were subsequently
suppressed by administration of PegIFN/RBV. Consequently,
telaprevir was administered in combination with PegIFN/RBV