Rules-Based Medicine has commercialised a new biomarker panel to aid pharmaceutical and biotech companies evaluate renal toxicity in rats for pre-clinical drug trials
RBM's Rat Kidney MAP (multi-analyte profile) measures key biomarkers found in urine that can provide additional information about drug-induced damage to kidney cells, known as renal toxicity or nephrotoxicity.
Development of the new renal safety biomarkers for regulatory decision making included in RBM's Rat Kidney MAP was directed by Novartis as part of one of the first Cooperative Research and Development Agreements (Crada) granted under the FDA's Critical Path Initiative.
The data and the assays were subsequently shared with the Predictive Safety Testing Consortium (PSTC).
The PSTC, whose members consist of scientists from 16 institutions, including 13 major pharmaceutical companies, was organized and led by the Critical Path Institute (C-Path), a nonprofit organisation founded to support FDA research collaborations that improve the development of medical products.
RBM developed and validated a panel of 12 new biomarkers connected with renal toxicity to support advanced laboratory methods to predict the safety of new treatments before they are tested in humans.
Using this new Rat Kidney MAP panel, RBM processed over 4000 test samples supplied by Novartis from rats dosed with multiple different known kidney toxicants.
That data was combined with data from Merck and other members of the PSTC to determine the panel's effectiveness for detecting renal toxicity.
Novartis and Merck analysed the results and determined that many of these biomarkers are effective in screening drugs to better understand potential side effects before the drugs enter clinical testing in humans.
The PSTC submitted the data to support the use of the new nephrotoxicity biomarkers to regulatory agencies in the US and the EU.
The FDA and the European Medicines Agency (EMEA) have recently published reports endorsing the use of these biomarker tests for pre-clinical trials.
"The FDA and EMEA findings support a number of truly ground-breaking steps, not the least of which is that a multiplex panel of biomarkers can be used in regulated safety studies under GLP conditions," said William B.
Mattes, director of toxicology for the Critical Path Institute.
"Sponsors can be confident as to the how the biomarker data will be interpreted by regulators and what will be considered acceptable uses".
Using predictive safety biomarkers in early animal and laboratory studies will improve drug safety screening, help researchers select initial human doses with more accuracy, and provide better monitoring for side effects prior to human clinical trials.
"When we have a number of drug candidates, we will be able to select the safest candidate for development, because we now have improved measures of renal safety," said Frank Dieterle, head of external affairs and safety biomarkers, iTox, Novartis.
"The use of the biomarkers will become routine when we have the slightest concern from pre-clinical studies that a drug might be nephrotoxic".
Prior to the Rat Kidney MAP, evaluating renal toxicity in animals and humans was limited to two biomarkers: blood urea nitrogen (BUN) and serum creatinine, long considered the gold standard in measuring kidney damage.
While effective, these traditional kidney biomarkers are insensitive and only indicate general kidney damage.
In contrast, the biomarkers in the Rat Kidney MAP are more sensitive, detecting cellular damage earlier as well as pinpointing which parts of the kidney have been affected.
With this new information, drug developers will detect kidney toxicity much earlier, allowing for either the adjustment of dosage or removal of toxic compounds from further development.
In either case, the efficiency of the drug development process is improved.
"We're pleased that our expertise in developing multiplexed biomarker panels is being recognized by pharmaceutical and biotechnology industry leaders," said RBM CEO Craig Benson.
"It was a great honour to be chosen to develop these important biomarker tests and to participate in the validation study for this project.
"We'd like to thank the FDA, EMEA, Novartis, C-Path and the PSTC for the vision and leadership that brought this unprecedented partnership together, and for their teamwork and diligence that have resulted in such a great success".
RBM is now accepting rat samples for testing in its Clia-certified central lab and will make a Rat Kidney MAP testing kit available through its worldwide distribution partner, EMD Biosciences, part of Merck, later this year.
The company also plans to introduce a companion product to the Rat Kidney MAP, the Human Kidney MAP.
RBM will begin accepting human samples in 3Q 2008.
