FDA News

Entelos, FDA to Collaborate on Computer Model to Better Predict Drug-Induced Human Liver Injury

(Aug 06, 2007)-- Entelos, a life sciences company building predictive computer models and “virtual patients” for drug discovery and development, today announced that it has entered into a Cooperative Research and Development Agreement (CRADA) with the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research (CDER).

“Early detection of potential drug safety problems is one of the objectives of the FDA’s Critical Path Initiative, an effort seeking to modernize the drug development process,” said Deputy Commissioner Janet Woodcock, M.D., the FDA’s Chief Medical Officer. “Under the Critical Path, the FDA is pursuing collaborations to find innovative ways to reduce the time it takes to bring new and therapeutically important medical products to the market.”

“The FDA has identified modeling and simulation and quantitative disease models as one of the important new methods to help bring a systems-level, mechanistic understanding of human biology that can lead to trial designs and early prediction of efficacy and safety,” Woodcock said.

Under the terms of the two-year agreement, Entelos will collaborate with the FDA to develop a computer model of drug-induced liver injury (DILI). The platform development plan has been designed by Entelos and the FDA with input from an expert scientific panel and a number of pharmaceutical companies. The goal is to use this platform to guide the development of clinical biomarkers and preclinical assays to identify patient types and drug combinations that increase the risk of developing liver injury. DILI is the most frequent cause of acute liver failure in the United States, and the single greatest cause of regulatory action, including failure to approve, withdrawal from the market, restrictions on use, and warnings to physicians.

“We are excited to announce our collaboration with the FDA on this most significant safety issue,” said James Karis, President and CEO of Entelos. “According to experts, the liver appears to be the most common target organ for toxicity during the course of drug development, and animal studies appear to be limited at best in predicting human hepatotoxicity. There is clearly a need to better understand the mechanisms of liver injury in man so that molecular or cellular screening assays and biomarkers can be developed to identify problems earlier. This DILI computer model will focus on defining healthy human liver function and creating a cohort of virtual patients to represent tolerator, adaptor, and susceptible patient phenotypes and predict what combinations make patients susceptible to hepatic injury following exposure to a specific drug or drug class. Such information will help patients, physicians, the FDA, and pharmaceutical companies avoid costly clinical failures and withdrawal of life-saving drugs from the market.”

To support its efforts, Entelos will partner with other members of the pharmaceutical industry. Details of the development and research plan, which was developed with scientific input from the FDA, are included in the Research Plan document. This document is available from Entelos for review and comment by other potential partners to this effort.

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