Biomarkers have tremendous scope to radically improve the safety and success rate of clinical trials but issues concerning intellectual property, and lack of investment are delaying progress, according to industry researchers at the recent Drug Information Association conference in Vienna.
At present, biomarkers are used in phase I and II trials but not in phase III because of concern about cost and of interpretability of results. With the benefit of hindsight, patients in the TeGenero TGN1412 trial, who suffered severe drug related side effects may have benefited if there had been available a suitably validated in vitro test.
Dr Larry Oliver, Scientific Director at Mayo Clinical Trial Services says that current validation criteria for biomarkers to identify patient response to trial compounds cannot fully assess toxicity. “The science still has some way to go before biomarkers can be used as extensively as clinical trial investigators would like,” he said. Analytical science needs to better mimic physiological conditions in the patients who will eventually receive the drug. “This is a combination of understanding disease markers better and matching physiological calibrators used in the assay to the form of the marker in the disease and then carry out a one on one biomarker check on the patient who will receive the drug.”
Biomarkers could have helped predict TeGenero trial
Analytical work conducted on the TGN1412 compound after the Northwick Park incident found conditions that more closely mimicked the physiological response and, had those tests been available, may have improved the prediction of the proper dose. “Improvements in analytical science would have provided more knowledge and predictability about the reaction of TGN1412 in humans instead of predominantly relying on animal results.”
But cost and issues around IP are slowing the adoption of new technology.
“Conducting tests to determine whether a particular compound under trial reacts differently in variable conditions according to indication and the patient population will cost time and therefore money so laboratories and pharmaceutical companies need to start negotiating around this,” explains Dr Oliver. Furthermore, at the moment there is no unanimous agreement over who would own the IP relating to a biomarker and any assay developed to predict potential patient response to the drug. By Becky McCall in Vienna, Austria