By Liz Highleyman

Ribavirin has been proven to reduce the likelihood of relapse and improve the rate of sustained response to interferon-based therapy for chronic hepatitis C virus (HCV) infection. However, ribavirin can cause hemolytic anemia, which may necessitate dose reduction or discontinuation

Taribavirin (formerly known as viramidine) is an oral pro-drug of ribavirin that is less likely to cause anemia. Previous Phase III studies (VISER1 and VISER2) produced disappointing results using a fixed dose approximately equivalent to 13-18 mg/kg/day. However, data suggested that the efficacy of taribavirin might be improved with both higher and weight-based doses. Likewise, ample evidence has shown that adequate weight-based doses of ribavirin are critical for successful treatment outcomes.

In the present study, presented at the 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008) last month in Milan, investigators set out to assess the safety and efficacy of weight-based taribavirin in combination with pegylated interferon.

In this open-label Phase IIb trial, 278 treatment-naive patients with genotype 1 chronic hepatitis C stratified by body weight and baseline viral load were randomly assigned (1:1:1:1) to receive taribavirin at doses of 20, 25, or 30 mg/kg/day, or else weight-based ribavirin (800, 1000, 1200, or 1400 mg/day), all administered with pegylated interferon alfa-2b (PegIntron). Baseline patient characteristics were generally similar across the study arms with regard to factors predictive of treatment response.

The primary efficacy outcome was the proportion of patients at week 12 with either undetectable HCV RNA (< 100 copies/mL) or a decrease of at least 2 log from baseline. The primary safety outcome was incidence of anemia (hemoglobin < 10g/dL).

Results

• At week 4, rapid virological response rates were:

• Taribavirin 20 mg/kg: 49%
• Taribavirin 25 mg/kg: 50%
• Taribavirin 30 mg/kg: 35%
• Ribavirin (all doses): 43%

• At week 12, early virological response rates were:

• Taribavirin 20 mg/kg: 64%
• Taribavirin 25 mg/kg: 57%
• Taribavirin 30 mg/kg: 54%
• Ribavirin (all doses): 51%

• Rates of anemia at week 12 were:

• Taribavirin 20 mg/kg: 9%
• Taribavirin 25 mg/kg: 7%
• Taribavirin 30 mg/kg: 15%
• Ribavirin (all doses): 24%

• The most common adverse events reported through week 12 were fatigue, nausea, flu-like symptoms, headache, and diarrhea.

• The incidence rates of these adverse events were generally comparable, except for diarrhea, which was reported approximately twice as often in the taribavirin arms.

• Diarrhea was generally mild and not dose-limiting.

Conclusion

"The data from this Phase IIb study demonstrated comparable efficacy between weight-based dosing of taribavirin and ribavirin," the investigators concluded. "Taribavirin at 20 and 25 mg/kg had a statistically lower anemia rate than ribavirin with overall similar tolerability."

They added that, "These results suggest that weight-based dosing of taribavirin at higher doses may be an alternative to ribavirin for the treatment of hepatitis C with an advantage for anemia."

Cedars-Sinai Medical Center, Los Angeles, CA; Alamo Medical Research, San Antonio, TX; Valeant Pharmaceuticals North America, Aliso Viejo, CA.

5/09/08

Reference
F Poordad, E Lawitz, E Chun, and others. Treatment week 12 results of weight-based taribavirin versus weight-based ribavirin, both with peginterferon alfa-2b, in naive chronic hepatitis C, genotype 1 patients. 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008). Milan, Italy. April 23-27, 2008.

Additional Sources

Valeant Pharmaceuticals. Valeant Pharmaceuticals Highlights Taribavirin Phase IIb Data Presentation at European Association for the Study of Liver (EASL) Annual Meeting. Press release. April 24, 2008.

Valeant Pharmaceuticals. Valeant Pharmaceuticals Reports Encouraging Phase IIb Results at Treatment Week 12 for Taribavirin. Press release. March 17, 2008.