Prodrug Taribavirin Produces Equivalent Response, but Less Anemia than Ribavirin

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Prodrug Taribavirin Produces Equivalent Response, but Less Anemia than Ribavirin at 48 Weeks In late November, Valeant Pharmaceuticals announced 48-week end-of-treatment data from a study of taribavirin, in combination with pegylated interferon, for the treatment or chronic hepatitis C virus (HCV) infection.

Taribavirin (formerly known as viramidine) is an oral prodrug of ribavirin, which helps reduce the risk of relapse after completing interferon-based therapy. Compared with ribavirin, however, taribavirin is less likely to cause hemolytic anemia, a side effect that often necessitates ribavirin dose reduction or discontinuation. But taribavirin is more likely to cause diarrhea.

Week 12 results from the study were presented this past April at the annual meeting of the European Association for the Study of the Liver (EASL 2008). Week 24 data were presented last month at the 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008).

Below is an edited excerpt from the recent Valeant press release describing the week 48 findings:

Valeant Reports Encouraging End of Treatment Results with Taribavirin at Treatment Week 48 in Phase IIb Study

Continues to Demonstrate Similar Efficacy to Ribavirin with Lower Anemia Aliso Viejo, Calif. November 24, 2008 -- Valeant Pharmaceuticals (NYSE:VRX) today reported results at end of treatment, week 48 analysis point in the Phase IIb clinical trial for its antiviral compound, taribavirin, a prodrug of ribavirin in development for the treatment of chronic hepatitis C in conjunction with a pegylated interferon. Similar to the treatment week 12 results reported earlier this year, the 48-week viral response (EOT) data continue to show comparable reductions in viral load for weight-based doses of taribavirin and ribavirin. The anemia rate was statistically significantly lower for patients receiving taribavirin in the 20 mg/kg and 25 mg/kg arms versus the ribavirin control arm. In the Phase IIb study, 278 treatment-naive, genotype 1 patients were randomized with the following patient demographics: mean age 48.8 years, 61.1% male, 30% African-American or Latino, 80.7% viral load ? 400,000 IU/mL and 82.1 kg mean weight. Treatment week (TW) 48 efficacy and safety results for the intention-to-treat (ITT) population are shown in the table below. Key Efficacy and Safety Data Table at Treatment Week 48 (ITT Population)

Phase IIb

Taribavirin20 mg/kgn=67

Taribavirin25 mg/kgn=70

Taribavirin30 mg/kgn=68

Ribavirin800-1400mgn=70

TW4 Undetectable1

11 (16.4%)

10 (14.3%)

11 (16.2%)

8 (11.4%)

TW12 Undetectable1

28 (41.8%)

29 (41.4%)

17 (25.0%)

22 (31.4%)

TW24 Undetectable1

35 (52.2%)

29 (41.4%)

27 (39.7%)

28 (40.0%)

TW48 Undetectable1

29 (43.4%)

23 (32.9%)3

20 (29.4%)

23 (32.9%)

Anemia rate TW 482

9 (13.4%)*

11 (15.7%)**

19 (27.9%)

23 (32.9%)

1 HCV RNA < 39 IU/mL

2 Anemia rate defined as percentage of patients with Hgb level < 10g/dL.

3 Includes data on two patients who were virus undetectable at TW36 and FW52, but missed TW48 assessment

*p=0.009

**p=0.03

"The results of this phase II study are encouraging, and suggest that comparable efficacy on therapy can be achieved when compared to ribavirin," stated Fred Poordad, MD, Chief of Hepatology at the Center for Liver Disease and Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA. "If the sustained response rates are also similar with less anemia, this will be a significant step forward in the development of taribavirin." "We are pleased that the 48-week data continues to demonstrate sustained comparable efficacy between taribavirin and ribavirin given that the genotype 1 group is a difficult to treat population and a third of the patients in this study were either African-American or Latino," said J. Pearson, chairman and chief executive officer. "We believe that taribavirin will be a promising alternative to ribavirin in the treatment of chronic hepatitis C and, with Valeant's strategic shift away from the infectious disease market, we plan to out-license this compound in order to maximize its potential for these patients." The most common adverse events were fatigue, nausea, flu-like symptoms, headache, and diarrhea. The incidence rates among treatment arms were generally comparable except with respect to diarrhea, where diarrhea was approximately twice as common in taribavirin patients as ribavirin patients. However, the diarrhea was generally mild and not treatment limiting for taribavirin or ribavirin patients. The Phase IIb trial is a U.S. multi-center, randomized, parallel, open-label study in 278 treatment-naive, genotype 1 patients evaluating taribavirin at 20 mg/kg, 25 mg/kg, and 30 mg/kg per day in combination with pegylated interferon alfa-2b [PegIntron]. The control group is being administered weight-based dose ribavirin (800/1000/1200/1400 mg daily) and pegylated interferon alfa-2b. Overall treatment duration is 48 weeks with a post-treatment follow-up period of 24 weeks. About Taribavirin Taribavirin is an investigational compound that has not been found by the Food and Drug Administration (FDA) or any other regulatory agency to be safe or effective in the diagnosis, mitigation, treatment or cure of any disease or illness. It may not be sold or promoted in the United States unless and until FDA has approved a New Drug Application. Similar restrictions apply in other countries. About Valeant Valeant Pharmaceuticals International (NYSE: VRX) is a multinational specialty pharmaceutical company that develops, manufactures and markets a broad range of pharmaceutical products primarily in the areas of neurology and dermatology. More information about Valeant can be found at www.valeant.com.