( 1 - b - D - ribofuranosyl - 1H - 1, 2, 4 - triazole - 3 - carboxamidine)
Taribavirin (1-b-D-ribofuranosyl-1H-1, 2, 4-triazole-3-carboxamidine) is a synthetic nucleoside (guanosine)
analog under development for the treatment of patients with chronic hepatitis C. After oral administration,
taribavirin is rapidly absorbed, after which it is readily and extensively taken up by the liver and
converted into its active metabolite, ribavirin. As a result, this reduces exposure to red blood cells
(RBCs) and increases exposure to the liver, the site of HCV replication.
The introduction of ribavirin accounted for the greatest incremental advance in the treatment of HCV. The
combination of ribavirin and peginterferon alfa is currently the standard treatment for chronic hepatitis C.
Although this combination treatment is effective in achieving sustained viral responses (SVR) in more than
fifty percent of hepatitis C patients, it can be associated with dose-limiting anemia. Adherence to therapy
has been shown to play a major role in achieving a sustained viral response (SVR), and hemolytic anemia
caused by the accumulation of ribavirin in red blood cells substantially undermines adherence. Most patients
started on ribavirin therapy experience a rapid 2-3 g/dL decline in circulating hemoglobin levels during the
first four weeks of therapy, and roughly 20-30 percent of patients on combination therapy develop anemia
(<10 g/dL). Anemia often prompts ribavirin dose reduction or discontinuation, which may be associated with
lower SVRs.
Valeant has begun enrolling patients in a Phase 2b clinical study for its antiviral compound, taribavirin,
an oral nucleoside (guanosine) analog, for the treatment of chronic hepatitis C in conjunction with a
pegylated interferon. The Phase 2b is a multi-center, randomized, parallel, open-label study in 260
treatment-naive, genotype 1 patients and will evaluate taribavirin at 20 mg/kg, 25 mg/kg, and 30 mg/kg per
day in combination with pegylated interferon alfa-2b. There also will be a control group comprised of
ribavirin (800/1,000/1,200/1,400 mg daily) and pegylated interferon alfa-2b.
Valeant will perform analyses of the study data after all patients have reached the week 12 time point which
is the primary endpoint of the study. The results at week 12 are typically predictive of a full 48-week
treatment course. Based on the 12-week data, the company will decide whether to begin another Phase 3 study
at a more appropriate dose than used in the VISER studies. Additionally, if the week 12 data are
encouraging, the company intends to continue the current study for a full 48-week treatment course with a
post-treatment follow-up at week 72. The 12-week results are expected to be available and be released by the
end of the year.
This study is subsequent to two pivotal Phase 3 trials for taribavirin that completed in 2006. The VISER (Viramidine Safety and Efficacy Versus Ribavirin) trials included two co-primary endpoints: one for safety (superiority to ribavirin in incidence of anemia) and one for efficacy (non-inferiority to ribavirin in sustained viral response, SVR). (Read more about the VISER1 results and VISER2 results ).
Valeant posts protocol information for all ongoing Phase 2, 3, and 4 trials to the National Institutes of
Health's (NIH) ClinicalTrials.gov website. To learn more about the clinical trials that are under way or to
find out if a study is enrolling patients in your area, please visit
www.clinicaltrials.gov.
Hepatitis C is a highly infectious and potentially fatal disease that can be contracted through blood and
bodily fluid contact, and is one of the most prevalent chronic infectious diseases in the United States. The
hepatitis C virus (HCV) attacks the liver and can cause inflammation, scarring, failure and cancer in that
organ.
Treatment for chronic hepatitis C represents a significant unmet medical need. The World Health Organization
(WHO) estimates as many as 170 million people worldwide are infected by HCV. Of these, the Center for
Disease Control and Prevention (CDC) has estimated that approximately 10 million people are infected with
HCV in the United States, Europe and Japan, of which 3.9 million are in the United States and 2 million are
in Japan. HCV is the leading cause of liver transplantation in the United States, accounts for 30 percent of
end-stage liver disease and liver cancer, and is responsible for approximately 12,000 HCV-related deaths in
the United States per year. Currently, there is no approved vaccine to prevent hepatitis C.
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