Arizona Biosciences News

C-Path consortium shepherds first-ever FDA/EMEA collaboration

Compiled from media sources


In an unprecedented process facilitated by the Tucson-based Critical Path Institute (C-Path), a consortium representing 17 pharmaceutical firms has torn down a major barrier to faster, safer, and cheaper drug development. Both the U.S. Food and Drug Administration and the European Medicines Agency have approved new methods, developed by C-Path's Predictive Safety Testing Consortium, for discerning the potential kidney toxicity of drug candidates.

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Raymond Woosley, Critical Path
Institute President & CEO.
(Photo courtesy of C-Path)

In an unprecedented process facilitated by the Tucson-based Critical Path Institute (C-Path), a consortium representing 17 pharmaceutical firms has torn down a major barrier to faster, safer, and cheaper drug development.

Both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) have approved new methods, developed by C-Path's Predictive Safety Testing Consortium (PSTC), for discerning the potential toxicity of drug candidates. From now on, the FDA and the EMEA will accept data from seven new biomarker tests--measures of particular proteins found in urine that indicate renal toxicity, or damage to kidney cells.

"The development of these and other biomarkers can result in important tools for better understanding the safety profile of new drugs," said Janet Woodcock, director of FDA's Center for Drug Evaluation and Research. "We hope these biomarkers will lead to human tests that detect drug-induced kidney injury in people earlier than is now possible, and help healthcare professionals better manage potential kidney damage from drugs."

Previously, the FDA and EMEA had required drug companies to submit data from two blood tests to demonstrate that potential therapies will not cause kidney damage. While the blood tests accurately measure toxicity, they do so in delayed fashion: by the time the blood tests indicate toxicity after a week of treatment, the kidneys may have sustained severe damage. And the blood tests only provide general indication of kidney damage, without suggesting which types of kidney cells are sustaining injury.

The new tests for kidney biomarkers--the proteins secreted by the kidneys and detectable in urine--offer more immediate results and greater sensitivity. Instead of yielding results after days of treatment, the biomarker tests will indicate whether kidney cells are being damaged only a few hours after treatment begins, and the tests will pinpoint precisely which kidney cells a drug is impacting. Consequently, researchers using the new tests will be able to stop administering therapies that prove toxic sooner in the drug-development process, and based on the more-specific results will be able to more easily fine-tune compounds to avoid toxicity.

The approval of the new tests by the FDA and the EMEA represents a triumph for the nonprofit C-Path, which accepts no funding from pharmaceutical companies, on more than one front. First is the foundational achievement of forming the PSTC and showing that it can function effectively. The consortium, which C-Path established in 2006 with representatives of only a few drug companies, now includes more than 190 scientists from 17 of the world's largest pharmaceutical firms, which have all agreed to a once-unimaginable step: revealing to each other the safety regimens they follow in testing new drug candidates. With the FDA (and more recently the EMEA) serving in an observer role and C-Path functioning as a trusted third party, the companies have agreed to a procedure for evaluating each other's safety regimens.

In the case of the kidney biomarkers, scientists from New Jersey-based Merck & Co. and Swiss-based Novartis AG identified the seven biomarkers, evaluated them for accuracy and usefulness, and then shared their findings with the other PSTC members. Having pooled their data to achieve a critical mass of scientific evidence, the PSTC then submitted a single biomarker data application--rather than individual applications from each PSTC member firm--to the FDA and the EMEA, following a framework developed by the FDA and EMEA in 2004 called the Voluntary Exploratory Data Submission review process.

Until now, "the FDA [has given] approval for a new drug or device, but there has previously been no way to obtain approval for a new and better way to test a drug for its safety," said Raymond Woosley, C-Path's president and CEO, in the San Francisco Chronicle.

Actively involving both the FDA and the EMEA in the effort to help modernize the drug-development process is also an important accomplishment for C-Path. The two regulatory bodies will continue to make independent analyses of new processes and technologies like the renal biomarkers, but the fact that both agencies are present and accessible to PSTC members produces greater standardization and streamlines the development process. Looking forward, the drug developers are aiming to repeat the process for other kinds of biomarkers, producing new tests that would signal whether drug candidates might be producing heart or liver damage or proving carcinogenic.

For now, the kidney biomarker tests will not actually be applied in human clinical trials. The FDA and EMEA have initially approved the tests only for preclinical drug trials that look for renal toxicity in rats; human trials will still require the traditional blood tests, although researchers may use the new biomarker tests conjunctively.

PSTC members are now beginning work toward qualifying the biomarkers for use in human trials, though, and in the future the new tests may have still broader application, including the development of more powerful therapies that can be prescribed in a more individualized manner. Rather than prescribing weaker drugs deemed broadly safe, doctors may be able to monitor patients' tolerance and adjust dosages carefully and safely according to results from the tests and a range of personal characteristics. At the first sign of kidney damage, doctors could stop a therapeutic regimen, avoiding irreparable injury.

"If you can detect it early enough, you can make a potential catastrophe not happen," said Federico Goodsaid, senior staff scientist for the genomics group in the FDA's Office of Clinical Pharmacology, in the San Francisco Chronicle.

According to the FDA, the "Critical Path" refers to the historically lengthy and complicated process by which a potential drug, product, or medical device undergoes scientific scrutiny, achieves approval from regulatory bodies, and becomes a product. The Critical Path Initiative, launched in 2004 by the FDA, is an effort to modernize--and thereby shorten--that process by incorporating new technological advances and discoveries. C-Path, founded in 2005, has positioned itself as a neutral facilitator of the initiative.

In June 2006, for example, C-Path and the FDA jointly convened experts on the drug warfarin, a popular anti-clotting drug, examining ways to identify the genetic differences that affect how patients metabolize the drug, which is known in part for a therapeutic range that varies widely among patients. The work of those researchers, facilitated by C-Path, led directly to a mandate from the FDA that warfarin receive new labeling that encourages prescribers to consider performing a specific genetic test on patients to help calibrate dosing and avoid serious side effects.

For more information:

"FDA backs new tests to monitor drug safety," San Francisco Chronicle, 06/14/2008

"C-Path drug safety group yields clues to kidney damage," Arizona Daily Star, 06/12/2008

"FDA, EMEA to Accept Biomarker Data for Kidney Toxicity Studies," GenomeWeb News, 06/12/2008

"EMEA, FDA jointly qualify renal biomarkers," PharmaTimes, 05/21/2008

FDA may soon support biomarker tests," San Francisco Chronicle, 04/17/2008

FDA media release, 06/12/2008