Deleobuvir is another agent that has successfully
completed a few clinical trials and appears to be a
good combination agent with or without ribavirin.
In a dose finding trial that included ribavirin and an
protease inhibitor, the combination was found to have
a 100% response rate at 28 days at the 600 mg three
times daily dose of deleobuvir.25 The SOUND-C1 trial
combined faldaprevir, ribavirin, and deleobuvir for
24 weeks and patients that did not respond after 24
weeks of therapy had IFN added to their regimen.26
At the conclusion of the trial, 94% of patients in the
600 mg 3 times daily dosing of deleobuvir had SVR
24 weeks after treatment ended.
ABT-333 has shown promise in combination with
other experimental agents without interferon.27 In a
trial, ABT-333 was one of the medications added to
HCV regimens and the regimens containing ABT-333
were found to be very effective in treatment-naïve
and patients who have failed previous regimens.
NS5A inhibitors
NS5A is a protein that is important to replication
and virion assembly of the HCV.6 By binding to this
protein and inactivating it, the replication cycle of
HCV can be inhibited in a mechanism completely
different than any other available mechanism thus
reducing the chance of cross resistance. With this
protein being produced by many of the different
genotypes of HCV, it allows for the medications to
cover different genotypes of the virus. No agent
from this class has been approved, however a few
including daclatasvir, ledipasvir, and samatasvir, are
being studied in trials.
Daclatasvir is being studied in both traditional
interferon therapy combination28 and with other
newer agents.29 There is some concern with the
use of daclatasvir in patients that have failed prior
therapy as it appears to be much less effective in
patients that have already failed therapy compared
to treatment naïve patients.28 Bristol-Meyers Squibb
has applied for approval for daclatasvi