Virologic response rates of weight-based taribavirin versus ribavirin in naïve chronic hepatitis C genotype 1 patients

 Hepatology
Volume 9999 Issue 999A, Page NA
Published Online: 30 Jun 2010
Copyright © 2010 American Association for the Study of Liver Diseases

F Poordad 1 *, E Lawitz 2, ML Shiffman 3, T Hassanein 4, AJ Muir 5, B Bacon 6, J Heise 7, D Halliman 7, E Chun 7, J Hammond 7

1 Cedars-Sinai Medical Center, Los Angeles, CA, USA
2 Alamo Medical Research, San Antonio, TX, USA
3 McGuire Research Institute, McGuire Veterans Administration Medical Center, Richmond, VA, USA
4 Southern California Liver Centers, San Clemente, CA, USA
5 Duke Clinical Research Institute, Duke University, Durham, NC, USA
6 Saint Louis University School of Medicine, St. Louis, MO, USA
7 Valeant Pharmaceuticals North America, Aliso Viejo, CA, USA

email: F Poordad (fred.poordad@cshs.org)

*Correspondence to F Poordad, Cedars -Sinai Medical Center, Hepatology and Liver Transplantation, Los Angeles, California, United States

Keywords
anemia • erythropoiesis-stimulating agents • weight-based dosing • antiviral dosing • clinical trial

Abstract

BACKGROUND:
Ribavirin-induced hemolytic anemia can prompt dose reductions and lower sustained virologic response (SVR) rates in the treatment of chronic hepatitis C patients.

The study aimed to determine if weight-based dosing (WBD) of taribavirin (TBV), an oral pro-drug of ribavirin (RBV), demonstrated efficacy comparable to RBV while maintaining its previously demonstrated anemia advantage with fixed dose administration.

METHODS:
A US phase 2b randomized, open-label, active-controlled, parallel-group study was conducted in 278 treatment-naïve, genotype 1 patients stratified by body weight and baseline viral load. Patients were randomized 1:1:1:1 to receive TBV (20, 25, or 30 mg/kg/day) or RBV (800 -1400 mg/day) with pegylated interferon alfa-2b for 48 weeks.

RESULTS:
The SVR rates in this difficult to cure patient demographics (mean age 49 yrs; 61% male; 30% African-American or Latino; high viral load; advanced fibrosis; and mean weight 82 kg) were 28.4%, 24.3%, 20.6% and 21.4% in the 20, 25, 30 mg/kg TBV groups and RBV group, respectively. There were no statistical differences in the efficacy analyses. Anemia rates were significantly lower (p<0.05) in the 20 and 25 mg/kg/day TBV treatment groups (13.4% and 15.7% respectively) compared to RBV (32.9%). The most common adverse events in all groups were fatigue, diarrhea, and insomnia. Diarrhea, reported in 38% of TBV patients versus 21% of RBV patients, was generally mild and not dose-limiting.

CONCLUSIONS:
All TBV doses demonstrated efficacy and tolerability comparable to that of RBV, however the 25 mg/kg dose demonstrated the optimal balance of safety and efficacy. Anemia rates were significantly lower for TBV 20-25 mg/kg than RBV. These data suggest WBD with TBV provides a safe and effective treatment alternative to RBV for chronic hepatitis C. (HEPATOLOGY 2010.)

Received: 24 April 2010; Revised: 18 June 2010; Accepted: 22 June 2010

Digital Object Identifier (DOI)
10.1002/hep.23827 About DOI

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