Taribavirin Offers a Safe, Effective Alternative for Chronic Hepatitis C, Study Finds

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Taribavirin Offers a Safe, Effective Alternative for Chronic Hepatitis C, Study

Finds

ScienceDaily (Sep. 22, 2010) — Researchers at Cedars-Sinai Medical Center and 50

other centers found that weight-based dosing of taribavirin reduces rates of

anemia while increasing sustained virologic response (SVR) in patients with

chronic hepatitis C (HCV). Full details of this study are available in the

October issue of Hepatology, a journal published by Wiley-Blackwell on behalf of

the American Association for the Study of Liver Diseases (AASLD).

Chronic HCV is typically treated with ribavirin (RBV). When used in combination

with peginterferon alfa (peg-IFN), RBV significantly enhances on-treatment

virologic response and reduces relapse. However, RBV, particularly the

combination of interferon and RBV, is associated with hemolytic anemia, a

significant toxicity resulting from the accumulation of RBV in red blood cells.

Taribavirin (TBV), formerly known as viramidine, is a nucleoside analog and oral

pro-drug of RBV that is less able to enter red blood cells, and should therefore

be associated with significantly less anemia.

This theory was demonstrated in two previous phase 3 trials. While statistically

less anemia was observed in patients treated with TBV compared to RBV, the

primary efficacy endpoint of these studies, a non-inferior SVR between the TBV

and RBV, was not achieved. Detailed subgroup analyses of the data suggest fixed

dosing as opposed to weight-based dosing, and the selection of an inadequate

dose, are to blame. The present multi-center study explored several higher

weight-based doses of TBV to determine a dosage regimen that was able to deliver

comparable responses to RBV with fewer incidences of anemia.

A 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 at 51 centers in the United States between March 2007

and October 2008. 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.

The primary efficacy endpoint was early virologic response (EVR) defined as the

proportion of patients with at least a 2-log decrease from baseline in serum HCV

RNA levels at treatment week 12. Additional efficacy endpoints included SVR,

undetectable HCV RNA at treatment weeks 4, 24 and 48, and viral relapse for

those who were responders at the end of treatment. A total of 86 (41%) of TBV

patients and 25 (36%) of the RBV group completed treatment and follow up. The

most commonly cited reasons for premature withdrawal were lack of response (29%)

and adverse events (20%).

The present study demonstrated that weight-based dosing of TBV achieved

comparable efficacy to RBV as demonstrated by SVR. This was observed in all

three TBV weight-based dose treatment groups, which met the study's primary

end-point. Patients treated with TBV had less than half the anemia compared to

RBV treated patients. These results suggest weight-based dosing of TBV can

significantly improve the tolerability of HCV treatment while maintaining

efficacy. Specifically, the 25 mg/kg dose offered the optimal balance of

efficacy and safety in this patient population.

Notably, fewer patients treated with TBV required dose reductions (13-28%)

compared to 32% of patients treated with RBV. Less frequent dose modification in

patients treated with TBV may alleviate the need to utilize

erythropoiesis-stimulating agents (ESAs). Several studies have demonstrated the

use of ESAs can significantly decrease the need to dose reduce RBV and leads to

an improvement in the quality of life during HCV treatment, but fails to improve

the SVR. The use of ESAs also adds significant cost to HCV treatment and is

associated with serious adverse events including thrombosis and red cell

aplasia.

Lead investigator Dr. Fred Poordad concludes, " These data suggest TBV may be an

effective agent to substitute for RBV in the future and could be incorporated in

upcoming trials utilizing emerging small molecules for HCV treatment. "

Editorial author Dr. Kwo comments, " If TBV can be shown to preserve or

improve efficacy rates in combination with direct-acting antiviral agents (DAAs)

and Peg IFN, with lower rates of anemia, the use of TBV in these clinical

settings would be a welcome addition to the HCV armamentarium as we begin to

expand the HCV populations that we treat. TBV may have a role in populations

particularly sensitive to ribavirin-related anemia. However, with the

commencement of several trials comprising of multiple combinations of DAAs with

and without pegIFN/RBV, and the development of newer protease inhibitors with

potentially lower rates of anemia, the role of TBV remains less precisely

defined and could potentially have a finite life cycle. "

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Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff)

from materials provided by Wiley - Blackwell, via AlphaGalileo.

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Journal References:

1.Fred Poordad, Lawitz, L. Shiffman, Tarek Hassanein, J.

Muir, Bruce R. Bacon, Heise, Deanine Halliman, Chun, Janet Hammond.

Virologic response rates of weight-based taribavirin versus ribavirin in

treatment-naive patients with genotype 1 chronic hepatitis C. Hepatology, 2010;

DOI: 10.1002/hep.23827

2. Y Kwo, Rakesh Vinayek. The next step for taribavirin. Hepatology, 2010;

DOI: 10.1002/hep.23957