Fails to Show Non-inferiority to Ribavirin at Tested Doses, but
Causes Less Anemia
The pro-drug viramidine
did not work as well as ribavirin in combination with
pegylated interferon for treatment of chronic hepatitis
C, according to results of the ViSER2 study reported
in the January
2010 Journal of Hepatology. Viramidine was
significantly less likely to produce blood cell deficiencies,
but also caused more diarrhea.
is a decrease in the normal number of red
therapy for chronic hepatitis C virus (HCV) infection consists
of pegylated interferon plus
ribavirin. Ribavirin significantly lowers the risk of relapse
after treatment, but it can cause red
blood cell damage. More than 20% of patient lower their doses
or stop taking ribavirin due to anemia.
(previously known as taribavirin) is a pro-drug of ribavirin
that more directly targets the liver, and therefore is less likely
to cause anemia. In the ViSER2 trial, Patrick Marcellin and colleagues
evaluated the safety and efficacy of viramidine versus ribavirin
plus pegylated interferon alfa-2a (Pegasys) in chronic hepatitis
received the same dose of pegylated interferon (180 mcg), but
644 patients were randomly assigned to receive 600 mg twice-daily
viramidine, while the remaining 318 received 1000-1200 mg/day
weight-based ribavirin. Treatment duration was 24 weeks for people
with HCV genotypes 2 or 3 and 48 weeks for those with other genotypes.
of viramidine recipients achieved sustained virological response
(continued undetectable HCV RNA 24 weeks post-treatment),
compared with 55% of ribavirin recipients.
on these results, viramidine did not meet criteria for non-inferiority
improved efficacy was seen in people with higher viramidine
exposure on a mg per kg basis.
caused significantly fewer "hemoglobin events" than
ribavirin, (54% vs 80%, respectively; P < 0.001).
of other adverse events were similar in the 2 groups, except
diarrhea was more common in the viramidine arm (30% vs 16%,
respectively; P < 0.0001).
researchers concluded that, "Viramidine 600 mg [twice daily]
did not meet the primary efficacy non-inferiority end point but
met the safety end point."
they added, "[d]etermination of a viramidine dosage that
would yield superior efficacy over ribavirin is needed."
It is clear that weight-based dosing of ribavirin is superior
to a fixed dose, since it helps ensure that people of different
weights reach similar drug concentrations in the body. This study
suggests the same is true for the pro-drug.
late 2008, Valeant Pharmaceutical announced that at 48 weeks,
weight-based viramidine produced HCV viral load reductions comparable
to those of weight-based ribavirin. However, further information,
including SVR rates, have not been forthcoming.
Hôpital Beaujon, Clichy, France; California Pacific Medical
Center, San Francisco, CA; Crawford Long Hospital, Emory University,
Atlanta, GA; Valeant Pharmaceuticals, Aliso Viejo, CA; Fundacion
de Investigacion de Diego, Santurce, Puerto Rico.
and efficacy of viramidine versus ribavirin in ViSER2: Randomized,
double-blind study in therapy-naive hepatitis C patients. Journal
of Hepatology 52(1): 32-38 (Abstract).