Valeant Pharmaceuticals International

The products below have not been found by the FDA (or other regulatory bodies abroad) to be safe or effective for treating any disease or illness. Until such time as products are approved by the FDA (or appropriate regulatory agency in other countries), they may not be promoted or sold.

Taribavirin

Objective

To significantly improve the current standard of therapy for Hepatitis C patients

Introduction

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.

Taribavirin is currently under investigation in clinical trials for the treatment of chronic hepatitis C.

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Retigabine

Retigabine is being developed as an adjunctive treatment for partial-onset seizures in patients with epilepsy. It has an entirely new mechanism of action and works as both a potassium channel opener and potentiates the effects of GABA, which Valeant believes will be a key product advantage where poly-therapy is common.

Phase 2:

Phase 2 trials for retigabine included more than 600 patients in several dose-ranging studies compared to placebo. The results of the key Phase 2 study indicate that the compound is potentially efficacious with a demonstrated reduction in monthly seizure rates of 23-35 percent as adjunctive therapy in patients with partial seizures. The most common adverse events in the Phase 2 trials were somnolence, speech disorder and ataxia.

Phase 3:

Phase 3 trials for retigabine were initiated in 2005. Enrollment is ongoing.

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TARIBAVIRIN and RETIGABINE are products in clinical development. None of them have been found to be safe or effective for the treatment of any disease or illness. They may not be sold or promoted in the United States unless and until they are approved by the FDA. Similar restrictions apply in other countries.