Erik Lontok1, Patrick Harrington2, Anita Howe3, Tara Kieffer4, Johan Lennerstrand5, Oliver Lenz6, Fiona McPhee7, Hongmei Mo8, Neil Parkin9, Tami Pilot-Matias10, Veronica Miller1. 1. Forum for Collaborative HIV Research, University of California at Berkeley, Washington, DC. 2. Center for Drug Evaluation and Research, Office of Antimicrobial Products, Division of Antiviral Products, US Food and Drug Administration, Silver Spring, MD. 3. Merck Research Laboratories, West Point, PA. 4. Vertex Pharmaceuticals, Inc., Boston, MA. 5. Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 6. Janssen Infectious Diseases, Beerse, Belgium. 7. Bristol-Myers Squibb Research and Development, Wallingford, CT. 8. Gilead Sciences, Inc., Foster City, CA. 9. Data First Consulting, Inc., Belmont, CA. 10. AbbVie, Inc., Chicago, IL.
Abstract
UNLABELLED: Hepatitis C virus (HCV) drug development has resulted in treatment regimens composed of interferon-free, all-oral combinations of direct-acting antivirals. While the new regimens are potent and highly efficacious, the full clinical impact of HCV drug resistance, its implications for retreatment, and the potential role of baseline resistance testing remain critical research and clinical questions. In this report, we discuss the viral proteins targeted by HCV direct-acting antivirals and summarize clinically relevant resistance data for compounds that have been approved or are currently in phase 3 clinical trials. CONCLUSION: This report provides a comprehensive, systematic review of all resistance information available from sponsors' trials as a tool to inform the HCV drug development field.
UNLABELLED: Hepatitis C virus (HCV) drug development has resulted in treatment regimens composed of interferon-free, all-oral combinations of direct-acting antivirals. While the new regimens are potent and highly efficacious, the full clinical impact of HCV drug resistance, its implications for retreatment, and the potential role of baseline resistance testing remain critical research and clinical questions. In this report, we discuss the viral proteins targeted by HCV direct-acting antivirals and summarize clinically relevant resistance data for compounds that have been approved or are currently in phase 3 clinical trials. CONCLUSION: This report provides a comprehensive, systematic review of all resistance information available from sponsors' trials as a tool to inform the HCV drug development field.
Authors: Ashley N Matthew; Jacqueto Zephyr; Caitlin J Hill; Muhammad Jahangir; Alicia Newton; Christos J Petropoulos; Wei Huang; Nese Kurt-Yilmaz; Celia A Schiffer; Akbar Ali Journal: J Med Chem Date: 2017-06-19 Impact factor: 7.446