The US Food and Drug Administration (FDA) has approved the first phase of the Liver Toxicity Biomarker Study (LTBS), a collaborative project aimed at discovering biomarkers of human hepatotoxicity in the standard preclinical test used by pharmaceutical companies in the initial stages of drug development.
According to BG Medicine, the US biotech that is conducting the study jointly with the FDA’s National Center for Toxicological Research (NCTR), liver toxicity is the most common biological cause of drug failure in pharmaceutical development, affecting one in six compounds. The toxicity tests currently used by drug companies date back at least 40 years and often fail to pick up human hepatotoxicity before drugs move into the more costly stages of clinical development, BG Medicine says.
The first phase of the LTBS, which will last around nine months, was designed by the FDA and BG Medicine with input from academia and industry. Seven participating drug companies – Pfizer, Johnson & Johnson, Pharmaceutical Research and Development, Mitsubishi Chemical Holdings, Orion, UCB, Sankyo and Eisai – will serve on the Scientific Advisory Board and provide funding, while Applied Biosystems will supply biomarker discovery systems based on mass spectrometry.
The project was conceived in response to the FDA’s Critical Path initiative, which has placed biomarkers centre-stage in its efforts to modernise and streamline medical product development. The agency’s work programme in this area includes putting out draft guidance for industry on clinical hepatotoxicity by the end of the 2008 fiscal year.
In another acknowledgment of the need to improve early-stage drug testing, last year a consortium of eight leading pharmaceutical companies in the US took the unprecedented step of agreeing to share preclinical laboratory data. The Predictive Safety Testing Consortium, which also includes Pfizer and Johnson & Johnson, was established by the non-profit Critical Path Institute with support from the FDA.