September 24, 2010

Taribavirin May Be Safe, Effective for Chronic Hepatitis C

Laurie Barclay, MD

September 24, 2010 — Weight-based taribavirin (TBV) treatment was associated with a reduction in anemia and increased sustained virologic response in treatment-naive patients with genotype 1 chronic hepatitis C virus (HCV) infection, according to the results of a phase 2b, open-label, active-controlled, parallel-group, randomized study published online June 30 and in the October issue of Hepatology.

"Ribavirin [RBV]-induced hemolytic anemia can prompt dose reductions and lower sustained virologic response (SVR) rates in the treatment of patients with chronic hepatitis C," write Fred Poordad, MD, from Cedars-Sinai Medical Center in Los Angeles, California, and colleagues. "The study aimed to determine if weight-based dosing of [TBV], an oral prodrug of [RBV], demonstrated efficacy comparable to RBV while maintaining its previously demonstrated anemia advantage with fixed dose administration."

At 51 centers in the United States between March 2007 and October 2008, 278 treatment-naive patients infected with genotype 1 HCV were stratified by body weight and baseline viral load and randomly assigned 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.

"This study suggests that comparable SVR rates may be achieved with weight based taribavirin and peg interferon in a genotype 1 population," Paul Y. Kwo, MD, associate professor of medicine, Division of Gastroenterology/Hepatology, Indiana University School of Medicine in Indianapolis, and coauthor of an accompanying editorial, published online September 7 and in the October issue of the journal, told Medscape Medical News. "Thus, as we enter the era of direct-acting antiviral agents (DAAs) with PEG interferon and RBV, TBV is an agent that deserves study to see if it can be added to PEG interferon and DAAs to preserve or improve SVR rates with lower rates of anemia. "

This patient population used in this study was considered difficult to cure because of their demographics and clinical characteristics, including high viral load and advanced fibrosis. Mean age was 49 years, 61% were men, 30% were black or Latino, and mean weight was 82 kg.

SVR rates were 28.4%, 24.3%, 20.6%, and 21.4% in the 20-, 25-, and 30-mg/kg TBV groups and the RBV group, respectively. Efficacy analyses showed no statistical differences.

Compared with the RBV groups, the 20- and 25-mg/kg/day TBV treatment groups had significantly lower rates of anemia (32.9%, 13.4%, and 15.7%, respectively; P < .05). In all groups, the most commonly reported adverse events were fatigue, diarrhea, and insomnia. Although diarrhea was reported in 38% of patients receiving TBV compared with 21% of patients receiving RBV, this was generally mild and not dose-limiting.

Fewer patients treated with TBV required dose reductions (13% - 28%) compared with 32% of patients treated with RBV. Less-frequent dose modification in patients treated with TBV may reduce the requirement for use of erythropoiesis-stimulating agents.

"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," the study authors write. "Anemia rates were significantly lower for TBV given at 20-25 mg/kg than RBV. These data suggest weight-based dosing with TBV provides a safe and effective treatment alternative to RBV for chronic [HCV]."

When asked about study limitations, Dr. Kwo noted that despite the lower anemia rates, the drop-out rate for anemia was similar between TBV and RBV, possibly because of a small sample size.

"There are many populations that have great difficulty tolerating RBV now (those with advanced liver disease, older patients, patients who have undergone liver transplantation, human immunodeficiency virus/HCV-coinfected individuals, and patients with hemoglobulinopathies and chronic renal failure), and these are populations that could potentially benefit from TBV," Dr. Kwo concluded. "[In future studies], TBV should be added to PEG interferon and DAA agents to see if viral response rates can be preserved or improved with lower rates of anemia when compared to PEG interferon, RBV and DAA agents."

Valeant Pharmaceuticals employs 4 of the study authors. The other study authors have disclosed no relevant financial relationships. Dr. Kwo reports receiving grant support from Schering Plough, Merck, Vertex, Valeant, Abbott, Bristol Myers Squibb, Tibotec, Glaxo Smith Kline, and Gilead; consulting for Schering Plough/Merck, Idenix, and Human Genome Sciences; and consulting on the ad boards for Merck, Schering Plough, Vertex, Gilead, Anadys, Abbott, Human Genome Sciences, and Novartis. He also reports speaking and teaching for Schering Plough/Merck, Roche, Gilead, and Bristol-Myers Squibb.

Hepatology. Published online June 30 and September 7, 2010.

Source
 
Also See:
-- Weight-Based Dosing Best for New HCV Drug
-- Taribavirin Offers a Safe, Effective Alternative for Chronic Hepatitis C, Study Finds

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