New non-invasive MRI biomarker for liver disease could cut costs for drug trials
Oxford September 22nd, 2020. Latest research from Perspectum shows how a new non-invasive combined imaging and blood biomarker could accurately identify NASH in NAFLD patients, highlighting its benefits for screening in clinical trials.
Non-alcoholic steatohepatitis (NASH), the most severe form of non-alcoholic fatty liver disease (NAFLD), is a life-threatening disease with currently no approved drugs to treat it. Although pharmaceutical companies are striving to develop new NASH treatments, with more than 100 active interventional trials (ClinicalTrials.gov), so far candidate drugs have failed to gain FDA approval. A major challenge for drug trials is that participants must be diagnosed with NASH and advanced fibrosis, which currently necessitates liver biopsy. This makes it a painful process and expensive for drugs companies as the number of participants not meeting the histological criteria, the screen failure rate, is often high following biopsy. Accurate non-invasive tests to identify suitable trial participants are therefore greatly sought after, as they could provide pre-biopsy screening, a reduction in screen failure rates and improvement in participants’ drug trial experience.
A potential solution is offered by a new biomarker combining routine blood tests with multiparametric MRI (mpMRI) technology from Perspectum’s LiverMultiScan® cT1®. Liver cT1 measures fibro-inflammatory disease and recently was included in new guidance on the use of mpMRI to identify NAFLD patients who are likely to develop NASH. In the current study, the new combined biomarker, known as cTAG, accurately identified patients with and without fibrosis. By using cTAG to enrich the population selected for biopsy, screen failure rate could be reduced from 61% to 13%, and the chance of a selected trial participant meeting histological criteria was improved by 87%.
Manu Chakravarthy, M.D., Ph.D., Executive Vice President of Clinical Development and Chief Medical Officer at Axcella commented, "Identifying the right patients for NASH trials is necessary for effective and safe drug development but is not easy using clinical risk factors alone and liver biopsy is invasive and complicated with both sampling issues and risk to patients. Non-invasive tests (NITs) are critical for screening patients and they are also emerging as effective endpoint measures. The added value of combining NITs with clinical information is now showing great promise for screening as compared to the use of individual markers. The composite of cT1, AST and fasting glucose – cTAG—appears to be one such tool that could facilitate effective identification of suitable trial participants with the potential to minimize high screen failure rates.”
These results emphasise the benefits of using advanced image-based tests such as cTAG, to determine NASH status. By identifying those suitable for NASH clinical trial enrolment prior to biopsy, screen failure rate and the number of unnecessary biopsies can be reduced. Furthermore, as new NASH treatments become available, cTAG could be used to ensure their appropriate use.