To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Strategies for Development of New Anti-HCV Therapies: Presented at HEP-DART URL: http://www.pslgroup.com/dg/2193B6.htm Doctor's Guide December 18, 2007
By Barbara J. Rutledge, PhD LAHAINA, HAWAII -- December 18, 2007 -- Triple combination therapy for hepatitis C virus (HCV) will become the standard of care in the next few years, predicted a researcher speaking here at the HEP-DART 2007 Frontiers in Drug Development for Viral Hepatitis symposium. Compared with the current standard-of-care regimens, new oral anti-HCV agents would ideally show improved efficacy, with sustained viral response in both treatment-naïve patients and nonresponders, and has better tolerability, allowing for reduced treatment duration, explained presenter Yves Benhamou, MD, PhD, Associate Professor of Hepatology, Hôpital Pitié-Salpêtrière, Paris, France. Toxicity and drug resistance are expected to be major limitations in development of new oral anti-HCV agents. To minimise the risk of drug-resistant mutations, proof-of-concept studies should last only 5 to 7 days, which should allow sufficient time to measure antiviral activity, recommended Dr. Benhamou. "Monotherapy with new oral agents will not improve sustained viral response," he said. Monotherapy would likely show lack of efficacy and result in rapid development of resistance, probably within the first week of therapy, he added. When designing a trial, he said, the most important objective is not to get a drug approved but to cure more patients. Combinations of oral anti-HCV agents with different mechanisms of action and no crossresistance should be considered during drug development. However, at least over the next few years, new oral anti-HCV agents will most likely be developed in combination with pegylated interferon-alfa and ribavirin, the treatment that is currently considered the standard of care. Pivotal clinical studies with interferon-alfa and ribavirin have revealed several predictors of favourable response: HCV genotype 2 or 3, low baseline HCV RNA levels (<800,000 IU/mL), body weight <85 kg, age <40 years, non-African-American race/ethnicity, and absence of severe fibrosis/cirrhosis. Virological response after 4 weeks of treatment (rapid virological response) has proven to be the most important endpoint in predicting sustained viral response and optimising treatment duration, said Dr. Benhamou. The main goal in new anti-HCV drug development should be achievement of a sustained viral response rate superior to that of the standard-of-care treatment, rather than reduction of treatment duration. The drug resistance profile will be critical in choosing a development strategy for any new anti-HCV agent, and emergence of drug-resistance mutations should be extensively studied in vitro. Safety and efficacy of any new anti-HCV agent must be studied in the context of the triple combination regimen. The initial virological response, within the first 2 to 4 weeks of therapy, will determine the necessary duration of therapy. "A trial to identify the best sustained viral response and the optimal treatment duration must be designed, powered and performed prospectively," recommended Dr. Benhamou. "Avoid subanalyses." [Presentation title: "Navigating Dangerous Complexities: Antiviral Strategies for Clinical Trials for Hepatitis C"] --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. P\S\L shall not be liable for any errors, omissions or delays in this content or any other content on its sites, newsletters or other publications, nor for any decisions or actions taken in reliance on such content. --------------------------------------------------------------------------------------------- This news story was printed from *Doctor's Guide to the Internet* located at http://www.docguide.com --------------------------------------------------------------------------------------- Return to News Story Page This site is maintained by webmaster@pslgroup.com Please contact us with any comments, problems or bugs. All contents Copyright (c) 1998 P\S\L Consulting Group Inc. All rights reserved.