Optimal RBV dosages are essential in achieving a SVR.
Maintenance of RBV in the therapeutic regimen has been proven
to have an important additive effect in the overall success rate,
leading to both increased RVR and reduced rates of relapses (as
demonstrated by the PROVE-2 trial).
As described in chapter 1, the main impediment in the
administration of high-dose RBV is the dose-dependent
development of hemolytic anemia. Although the addition of
epoetin alfa has been useful in maintaining the highest possible
RBV doses, new RBV-replacement compounds, with an improved
side effects profile, are investigated.
Taribavirin – formerly known as viramidine – (Valeant
Pharmaceuticals International/Kadmon Pharmaceuticals LLC), is
a prodrug of RBV, converted in the active form by adenosine
deaminase. This nucleoside analog was studied for the treatment
of CHC, due to the lower frequency of anemia, a benefit
registered especially within the first 12 weeks of treatment, the
period in which maintenance of the dose of RBV has been shown
to be the most critical. The major conversion site of taribavirin is
in the liver, enabling drug concentration in this location. Due to
its lower uptake in red blood cells, taribavirin causes
significantly less hemolytic anemia compared to RBV. While this
effect was confirmed in several clinical studies, the rates of SVR
were lower with taribavirin.
In two phase III studies, taribavirin failed to prove
noninferiority compared to RBV (SVR rates were 38% and 40%
with taribavirin vs. 52% and 55% with RBV in the VISER 1 and
VISER 2 trials, respectively), even if taribavirin caused lower
rates of severe anemia (5% vs 24%). Suboptimal dosing of
taribavirin (Marcellin 2010) seems to be the explanation, as
recent studies with weight-based dosing of taribavirin confirmed
reduced rates of anemia (7%-15% vs. 24% with RBV), while
acquiring comparable SVR rates and lower relapse rates than
RBV. Whether taribavirin will have a role in the future
Searching for new antiviral therapies | 65
combination therapies including DAAs (most of which are also
associated with a certain degree of anemia) remains to be seen.
Maintenance of RBV in the therapeutic regimen has been proven
to have an important additive effect in the overall success rate,
leading to both increased RVR and reduced rates of relapses (as
demonstrated by the PROVE-2 trial).
As described in chapter 1, the main impediment in the
administration of high-dose RBV is the dose-dependent
development of hemolytic anemia. Although the addition of
epoetin alfa has been useful in maintaining the highest possible
RBV doses, new RBV-replacement compounds, with an improved
side effects profile, are investigated.
Taribavirin – formerly known as viramidine – (Valeant
Pharmaceuticals International/Kadmon Pharmaceuticals LLC), is
a prodrug of RBV, converted in the active form by adenosine
deaminase. This nucleoside analog was studied for the treatment
of CHC, due to the lower frequency of anemia, a benefit
registered especially within the first 12 weeks of treatment, the
period in which maintenance of the dose of RBV has been shown
to be the most critical. The major conversion site of taribavirin is
in the liver, enabling drug concentration in this location. Due to
its lower uptake in red blood cells, taribavirin causes
significantly less hemolytic anemia compared to RBV. While this
effect was confirmed in several clinical studies, the rates of SVR
were lower with taribavirin.
In two phase III studies, taribavirin failed to prove
noninferiority compared to RBV (SVR rates were 38% and 40%
with taribavirin vs. 52% and 55% with RBV in the VISER 1 and
VISER 2 trials, respectively), even if taribavirin caused lower
rates of severe anemia (5% vs 24%). Suboptimal dosing of
taribavirin (Marcellin 2010) seems to be the explanation, as
recent studies with weight-based dosing of taribavirin confirmed
reduced rates of anemia (7%-15% vs. 24% with RBV), while
acquiring comparable SVR rates and lower relapse rates than
RBV. Whether taribavirin will have a role in the future
Searching for new antiviral therapies | 65
combination therapies including DAAs (most of which are also
associated with a certain degree of anemia) remains to be seen.
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