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Experts Propose New Terminology for Hepatitis C Drug Trials
New Definitions Intended to Accelerate Innovation in Drug Development
WASHINGTON, DC (December 18, 2012) – At a time when drug discovery for new hepatitis C treatments is taking place at a rapid pace, medical researchers, pharmaceutical manufacturers, patient advocates and government regulators face a new scientific and regulatory hurdle: how to report the comparisons between drugs and regimens when accurate terminology to quantify virologic response is lagging.
Because outdated terminology has made it difficult to assess the clinical benefits of next-generation direct-acting antiviral drugs and combination therapies now in the pipeline, a new paper from the Forum for Collaborative HIV Research recommends the adoption of a standardized nomenclature that will bring simplicity and clarity to the field, allow for inter-trial comparisons and can be adapted to continuing advances in hepatitis C virus (HCV) drug development.
View the paper >>
“This is a watershed moment in the field of HCV therapeutic development. A range of promising new drugs in the pipeline appear to produce a more rapid virologic response with fewer side effects. That is why adopting a new nomenclature for the research community is so critical,” said Veronica Miller, Ph.D., Director of the Forum and one of the authors of the paper. “Our paper offers a new pathway for reporting key decision points in treatment trials and reflects the best thinking of the top experts in the field.”
Published in the journal Hepatology, the paper lays out a new set of terms that clearly describe virologic responses during the course of therapy for hepatitis C. The new terminology was developed by the Hepatitis C Virus Drug Development Advisory Group (HCV DrAG) and an international Definitions and Nomenclature Working Group to replace today’s qualitative descriptions with precise measures that define the virologic response by week of therapy and by the amount of virus remaining, based on standard quantitative molecular tests. Beyond clinical trials, this new terminology will aid in the development of treatment guidelines for clinical practice.
As described in the research paper, the new terminology uses descriptions of virologic responses that are more consistent across studies and can be adapted as response times become shorter. As such, the proposed nomenclature includes detailed information about each measure of an HCV treatment trial. The key components are the week of treatment, the quantifiable decline in viral load from initiation of treatment, the duration of any lead-in treatment before the trial begins (counted as days or weeks), and whether the target amount of hepatitis C virus in the person’s blood (called HCV RNA) is detected or not.
Reflecting the state of the science, where precise bioassay tests are able to measure very minute levels of hepatitis C virus in the blood (also called HCV RNA or viral load), the new terminology also distinguishes treatment responses in terms of quantifiable and unquantifiable levels of HCV RNA. Accordingly, existing definitions will be much more detailed and a number of new definitions – for Extended Rapid Virologic Response (eRVR), Very Rapid Virologic Response (vRVR), Complete Early Virologic Response (cEVR), and End of Treatment Response (ETR) – will be added to the lexicon.
The new definitions were developed by the HCV Drug Development Advisory Group (HCV DrAG) along with a panel of experts from the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL) and the Infectious Diseases Society of America (IDSA). A project of the Forum for Collaborative HIV Research, the HCV DrAG is comprised of representatives of Food and Drug Administration, European Medicines Agency, academia, the patient advocacy community and industry.
Donald Jensen, MD, professor of medicine at the University of Chicago Medical Center in Illinois who represented AASLD on the expert panel, reflected on the importance of these new definitions to the HCV research community. “We set out to develop a uniform reporting system that is intuitive, flexible and provides the specificity necessary to compare the virologic responses of different drugs and combinations consistently across clinical studies, which this new terminology makes possible,” he said.
Heiner Wedemeyer, MD, Research Group Leader in the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School in Germany and a former Secretary General of the European Association for the Study of the Liver (EASL), added: "The new terminology will accommodate the varied viral kinetic responses observed with the different regimens being studied and we urge everyone in the field to adopt this nomenclature when reporting trial results. If widely adopted, this new terminology has the potential to accelerate drug discovery and lead to more highly active anti-HCV therapeutic drug regimens.”
To underscore the need for this more precise system of interpreting clinical trial results, the new paper notes the major progress in HCV drug development, including the 2011 approval in the U.S. of two direct-acting antiviral drugs in combination with pegylated interferon and ribavirin (PEG-IFN/RBV) and nearly 20 agents in phase 2 and/or phase 3 trials with or without PEG-IFN or RBV. But the paper also reflects the challenge of accurately translating the results of HCV trials, especially when evaluating direct-acting antiviral drugs, which have potent antiviral actions and appear to produce a more rapid virologic response. Accordingly, the proposed changes in drug response terminology are designed to facilitate progress in clinical research so the estimated 170 million people with chronic hepatitis C infection will have access to newer, more effective treatment options.
The new scientific paper, “Recommendations for Hepatitis C Virus Clinical Trial Response Nomenclature and Definitions for Investigational HCV Agents,” appears in Hepatology Vol. 56, Issue 6, pages 2398-2403.