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FDA Initiative Aims to Bring Biomarkers To Forefront of Drug Development Process


As part of its Critical Path program to speed the movement of discoveries from bench to bedside, the US Food and Drug Administration has launched an initiative to bring biomarkers — including protein biomarkers — to the forefront of drug development, according to an agency official.

The FDA plans to issue guidelines to industry on what criteria are necessary in order for a biomarker to be used as a surrogate endpoint, and to promote the use of biomarkers systematically throughout the process of drug development.

“When we announced our Critical Path initiative in March, we received many comments in the public docket,” Lawrence Lesko, FDA’s director of clinical pharmacology and biopharmaceutics, told ProteoMonitor this week. “Many of them made suggestions for better use of biomarkers in the drug-development process.”

It is unclear so far how much funding will go into the new biomarker initiative, said Lesko, who also declined to say when the guidance would be made available to industry. The funding will come out of cash set aside for the Critical Path Initiative, a program announced in March that will be financed by the federal government, in addition to research collaborations with universities and cancer centers.

Surrogate endpoints are laboratory measurements or physical signs used as a substitute for a clinical endpoint that directly measures how a patient feels or functions. Biomarkers that are currently approved by the FDA for use as surrogate endpoints include CD4 levels for HIV progression; blood sugar level for diabetes; cholesterol level and blood pressure for atherosclerosis; and HER2 protein expression for breast cancer.

A number of companies have said that they intend to submit protein signature patterns to the FDA for approval as diagnostic tests, but no such signatures have yet been approved by the FDA, Lesko said.

According to Lesko, biomarkers are often used in preclinical trials, and in stage I and stage II clinical trials, but they are not usually used when drugs go into late-phase clinical trials because clinical outcome, rather than biomarkers, is what regulators and drug makers look for before a therapeutic enters the marketplace.

As part of the new initiative, the FDA seeks to encourage drug companies to monitor biomarkers throughout stage III and stage IV clinical trials. This can lead to the development of biomarkers as surrogate endpoints, and could make clinical trials shorter and less expensive.

“The ideal biomarker is one that a company would use throughout the drug-development process,” Lesko said. “The company would get approval based upon the biomarker as a surrogate endpoint, and then a diagnostic would be developed so that it could be used as patient care as well.”

In addition to issuing guidelines for surrogate biomarker and promoting biomarker monitoring throughout the clinical trial process, the FDA is also planning on developing an inventory of current surrogate endpoints.

“I don’t think the public really understands the breadth and scope of surrogate endpoints,” said Lesko. “We want to look at what is the evidence that supported these former biomarkers as surrogate endpoints. By doing this inventory it’s a good start to talk about the future.”

Lesko said the FDA plans to collaborate with the US National Institutes of Health, academia, and industry to develop biomarkers. For example, the agency currently has an agreement with the University of Arizona and the Stanford Research Institute to establish a drug-development institute with the goal of speeding the translation of drug research into products.

And as part of ongoing funding to promote early cancer detection, the US National Cancer Institute recently awarded $9.8 million in first year funding to 17 Biomarkers Developmental Laboratories that are part of the agency’s Early Detection Research Network.

Institutions that were granted funds include the University of Pittsburgh, Fox Chase Cancer Center, the University of Michigan, M.D. Anderson Cancer Center, Fred Hutchinson Cancer Research Center and Johns Hopkins University. A complete list of grantees is available at

Investigators at the Biomarkers Developmental Laboratories will examine the human genome, proteome, epitome, and metabolome to identify biomarkers that can potentially be useful for early disease detection and progression.

“The synergized power of DNA arrays, protein arrays, and bioinformatics are being used to help decipher hundreds of thousands of leads to discover unique signatures for early cancer,” said Sudhir Srivastava, chief of the cancer biomarker research group at NCI’s Division of Cancer Prevention.

The NCI received 68 applications to serve as Biomarker Developmental Laboratories, of which 17 were selected for funding. About 40 percent of grantees are new to the EDRN. The rest are extending their 5-year funding from the NCI, which began in 1999. The current round of funding will last for another five years.

With the FDA’s current initiative, the agency hopes to approve biomarkers, such as those discovered by the EDRN, for use as surrogate endpoints based on clinical and epidemiological data. The use of clinical data should reduce the amount of time it takes for a surrogate endpoint to be approved, which would speed the development of diagnostic tests based on biomarkers.

“With blood sugar for diabetes; cholesterol for atherosclerosis — those surrogate endpoints were based on epidemiological data, post-drug approval,” said Lesko. “With the new FDA guidelines and initiative, we hope to approve surrogate biomarkers in real time, based on clinical study data.”


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