History has been made. The FDA and the European Medicines Agency (EMEA) have reviewed biomarkers together and agreed. For the first time. Ever.

That’s according to Raymond Woosley, president and CEO of the Critical Path Institute (CPI), an Arizona-based public-private partnership that’s trying to, among other things, get industry (pharma and biotech) and government regulators (FDA, EMEA, and potentially others) to review and agree on new biomarkers for testing drug safety. (You can find a few more details in a ClinPage news brief.)

Kidney Focus

CPI, through its Predictive Safety Testing Consortium (PSTC), managed to get the two big regulating bodies to review biomarkers for drug-induced kidney injury in animals. Out of the 10 they saw, they liked seven. Woosley was psyched.

“This is the first step toward global review of data,” he said.

Perhaps even more remarkably, CPI has drug makers working together, too. “It’s also the first time 14 drug companies have submitted anything to the FDA together,” bragged Woosley, smiling.

Ancient Science

CPI is a non-FDA organization intended to push the science of drug discovery forward in a way that helps industry and the FDA. The mission is to collaborate with all parties to help the FDA implement its Critical Path Initiative. Within that bigger picture is CPI’s safety consortium, which is comprised of 200 scientists from pharmaceutical companies, non-profit research organizations, the FDA and the EMEA. 

Why start with the kidney? Because, said Woosley, many renal tests are antiquated, bordering on obsolete. One had been developed a century ago, and doesn’t show damage until 70 percent of kidney function is lost. Of the 28 tests used in this area, only seven are adequate, said Woosley. It was time for far more sensitive tests.

The new tests emanating from PSCT measure the levels of seven key proteins or biomarkers found in urine that can offer more information about renal toxicity.

Regulatory Issue

Another issue is regulatory ambiguity. Drug development companies can spend lots of money in trying to move forward on developing biomarkers, but without any formal blessing and consensus from FDA.

“There have been billions of dollars spent and lots of research done on biomarkers,” said Woosley. “In order for those biomarkers to be used, the companies have generally just guessed at whether the FDA would accept them, and hope then that their application for a drug or device would be accepted. And then they would find out [the biomarker they used] isn’t a validated biomarker.”

27 Lawyers

That’s frustrating for industry and regulators. Explained Woosley, “FDA reviewers were saying, ‘A company comes along with new data saying how safe their drug is, and gosh, I’ve got another company with a different method saying the same thing. Which is right?’”

The key was to get everyone together: industry and regulators. This wasn’t simple. Woosley said the early conference calls—think 200 scientists dialing in—were unique, to say the least. Initially, everyone was nervous about intellectual property, and antitrust issues. At one point, there were 27 lawyers also on the call. Everyone was guarded, not sure what to say and not say.

The organization then hired a single lawyer to come up with a consortium agreement. In a nutshell, it said that if the scientists shared their information on biomarkers in a specific way, antitrust issues would not arise. For the FDA’s sake (the FDA was on the calls, too) talk of specific products had to be left out as well.

Arizona Funding

As soon as all that was settled, and the legalities were out of the way, everyone was eager to collaborate. “The scientists went crazy talking science,” said Woosley. CPI is an independent body; industry does not fund it. “If we ask these companies to pay us to do this, we’ve lost our credibility,” said Woosley.

Instead, Arizona does. The state has funded CPI to the tune of $11 million over five years. The organization is three years into that, and currently sending out grant applications to stay funded after that. d9A2t49mkex

In addition, many of the participating industry scientists say they are spending money within their companies—about $25 million collectively, said Woosley—to come up with the data to share.

CPI has 22 employees, 17 of which are in Tucson, AZ, and five of which work in Rockville, MD.

Start Slow

Yes, the newly agreed-upon renal biomarkers that CPI is so excited about have been qualified for animals only. But, said Woosley, this is the first critical step toward their use in clinical drug development. And when you’re dealing with huge regulating bodies, it’s important to take baby steps.

“Try to do too much and you jeopardize the whole thing with respect to the FDA’s role as regulator. Just because these tests look really good in rats, you can’t expect the FDA to approve them in anything else. Yet,” he said.

Next up? Looking at the biomarkers in humans, of course. And if that process proves successful, the regulators and sponsors will be able to move products toward the market with more speed and insight. “The commercial side can use it to decide whether they want to take a drug to the next phase or not,” Woosley said. “For the FDA, it can be used to make regulatory and development decisions.”

—by Suz Redfearn

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