Page 69 - The Flying Publisher Guide to Hepatitis C Treatment

Searching for new antiviral therapies | 69

virologic response at the end of the lead-in phase is highly
predictive for the final outcome of therapy. Substantially higher
SVR rates are obtained in patients showing more than 1 log 10
decline in HCV RNA at this time point. Even in patients with a
poor response to interferon, addition of boceprevir can generate
a SVR in up to 34% of the patients. This is an important
information, arguing for the utility of a lead-in phase in the
previously treated nonresponders or relapsers. For naive
patients, the lead-in period can further serve to test both
compliance and tolerability before exposure to PIs.
The most commonly reported AEs with boceprevir were anemia
(almost twice as many boceprevir recipients had Hb levels <9.5
mg/ml compared to controls) and dysgeusia (more than twice as
often in boceprevir recipients than in controls). Serious AEs were
reported in 11% of patients receiving boceprevir in combination
with PegIFN/RBV compared with 8% of patients receiving
PegIFN/RBV alone. The most common reason for dose reduction
in the trials was anemia.

Other investigational HCV PIs
A series of additional PIs are in development and preliminary
studies confirm their superior antiviral effectiveness in
combined triple therapy over the SoC in treatment-naive
patients. Unlike telaprevir or boceprevir, which are active only
on genotypes 1 and 2 and have to be dosed three times a day,
investigational second-generation PIs, mainly non-covalent
inhibitors of the NS3/4A, seem to be active against different HCV
genotypes, as well as against resistant HCV variants previously
selected by other PIs. Also, they have a longer half-life which
enables more convenient once-daily dosing. In addition, they
may provide improved safety and efficacy as well as shortened
treatment duration for a higher proportion of patients. An
example is BI 201335, a once-daily HCV NS3/4A protease
inhibitor optimised to target genotype-1 HCV, with strong in
vitro activity also against GTs 4-6. Phase II studies showed
BI 201335 to have strong efficacy, with overall SVR rates