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

[Guest guest]

http://www3.interscience.wiley.com/journal/123568202/abstract

Hepatology

Volume 9999 Issue 999A, Page NA

Published Online: 30 Jun 2010

American Association for the Study of Liver Diseases

Viral Hepatitis

Virologic response rates of weight-based taribavirin versus ribavirin in naïve

chronic hepatitis C genotype 1 patients

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

1Cedars-Sinai Medical Center, Los Angeles, CA, USA

2Alamo Medical Research, San , TX, USA

3McGuire Research Institute, McGuire Veterans Administration Medical Center,

Richmond, VA, USA

4Southern California Liver Centers, San Clemente, CA, USA

5Duke Clinical Research Institute, Duke University, Durham, NC, USA

6Saint Louis University School of Medicine, St. Louis, MO, USA

7Valeant Pharmaceuticals North America, Aliso Viejo, CA, USA

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

*Correspondence to F Poordad, Cedars -Sinai Medical Center, Hepatology and Liver

Transplantation, Los Angeles, California, United States

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