Life science computer modelling expert Entelos, is to collaborate with the FDA to develop a method of using in silico data to aid in the development of preclinical assays and clinical biomarkers that could identify patient types and drug combinations that increase the risk of developing liver injury. The company has previously developed an in silico model for diabetes that 'maps' data from preclinical animal studies onto a 'virtual human' to allow better prediction of human responses. The two-year collaboration to develop a computer model of drug-induced liver injury (DILI) is part of the FDA's 'Critical Path Initiative' that is aiming to reduce the time it takes to develop therapeutically important medical products and bring them onto the market. DILI is the most frequent cause of acute liver failure in the US and the biggest reason for new drug application failures, drug withdrawals and restrictions on use. In 2004, Stephen Williams, Pfizer's head of global clinical technology, said the company had wasted $2bn over the last decade on drugs that failed in clinical trials or were withdrawn from the market due to liver toxicity problems. With the pharma industry being criticised for its lack of productivity and the rising cost of expensive failures, such as Pfizer's Torcetrapib , the need for better methods of assessing the toxicity of drugs earlier in the drug discovery process has never been more evident. "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," said James Karis, CEO of Entelos. The DILI computer model will focus on defining healthy human liver function and create a cohort of healthy patients to represent 'tolerator, adaptor and susceptible patient phenotypes' and predict what combinations make patients susceptible to liver damage following exposure to specific drugs or drug classes. "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," said Karis. NanoBioDesign is currently in the process of industrialising one such assay tool that uses the P450 enzymes that are responsible for primary drug metabolism immobilised on electrode surfaces to see if a drug activates the enzymes.
The search for better models to predict drug-induced human liver damage has led the FDA (US Food and Drug Administration) to turn to Entelos to design a 'virtual liver' to guide biomarker and assay development.