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The C-Path Institute s Ray Woosley on Critical Path Projects

Ray Woosley
C-Path Institute

Name: Ray Woosley

Background: President, C-Path Institute, since 2005; Vice President for the University of Arizona Health Sciences Center, 2001 — the present; Associate Dean and Dean, University of Arizona College of Medicine, 2001 — the present; Chairman, Department of Pharmacology, Georgetown University, 1988 — 2001

Education: PhD, Pharmacology, University of Louisville, 1967; MD, University of Miami, 1971

The Critical Path Institute is a joint project of the University of Arizona and SRI International under the guidance of the US Food and Drug Administration to conduct research and educational programs associated with the Critical Path Initiative.

The institute has a major role in two projects for which the FDA issued requests for applications that accompany its release last week of the Critical Path Opportunities List (see story, this issue). The C-Path Institute is working to establish the infrastructure for the warfarin-related Collaborative Cardiovascular Drug Safety and Biomarker Research Program, and it plays the role of mediator between pharma companies in the Predictive Safety Testing Public/Private Consortium.

Pharmacogenomics Reporter this week spoke to Ray Woosley, the institute's president and CEO, this week to learn more about the status of the Critical Path Initiative.

Can you give me some background on the Opportunities List?

A couple of years ago, [the FDA] came out with a white paper [on the Critical Path initiative], and they wanted to release this list for quite a while, but they have no budget for process improvement, so they've had to compile this list without any resources. People complain because it took so long, but I'm amazed they were able to do it at all without any funding.

But it's an excellent list. We've been working with them — we started interviewing folks there over a year ago about projects that we might be able to facilitate under our collaborative agreement. And one of the ones the FDA brought to us early on was what we call 'predictive safety testing' — the other name is 'toxicogenomic cross-validation consortium.' So for your readers, they might be able to understand that one better than the one we gave the public.

The idea came about because the reviewers in pharm/tox at the FDA were getting applications from companies saying, 'Here's our tox workup, these are the methods we used, we think it's going to really be safe, let us get into human testing as fast as possible.' And [the FDA] would say, 'That's fascinating, that's really good science, but it's science you've developed inside your company and we've got other companies saying their drugs are safe and they use totally different methods. So how do we know which method's the best?'

They gave us the names of six companies — eventually a bunch of others found out about it, so we've got eight now — that have agreed to sit down with us and who've actually had their first meeting, where they share with each other and the FDA the methods they use for specific kinds of preclinical tox. And they've agreed to test each other's methods, so that if one company developed a method, another company will take it and see if they can get the same results.

[They] submit the data back to C-Path, and we're neutral territory. We haven't accepted any money from the companies, and we're simply facilitating the process, so we will summarize those data, and the agency can decide what kind of guidance they would write.

The guidance would say, 'Here are the methods we think are validated now, by two different companies, with oversight. And here are the methods we don't think you should be using any more because they've been replaced,' and hopefully that'll save time and money.

The companies are really excited about sharing their science, what they've learned in this research, what they can learn from each other, and I think the public is really going to benefit by having greater knowledge within the industry and within the agency, about what kinds of tests are most predictive of safety.

What's the next step for the Critical Path, now that the Opportunities List has been published?

Well, for us, which is all I can say, the next step is going to have to be that the FDA gets some money to work on these things. The President is asking for $6 million in the next year's budget, so they'll have staff to work on these initiatives. That's a pittance. That's an embarrassing number, but it's better than nothing. But the agency has found, and we've found scientists within the agency willing to work at night and weekends to help us plan these projects.

So we're going to be looking at other projects. We've got a project with their Pharmacogenomics Group on warfarin that we were able to get directed funding into this year's budget. That will be with the University of Utah to evaluate genomically based dosing of warfarin compared to conventional warfarin dosing.

Has that already started?

It's already underway. They've already enrolled 20 patients into the trial. They're doing it with their own funding, but it'll be part of our collaborative project with the FDA.

That's with Jeffery Anderson, an old friend of mine at Utah. We've been wanting to do this project for years, he put in an application, the agency put out an RFP for this project, but they didn't have enough money to fund it. So he and I are funding it on our own.

Through C-Path?

C-Path and Utah are jointly funding the start of it. Within the next few months, though, we should have federal funding to really take it to completion.

That's a project that I think everybody's been waiting for. All the work in pharmacogenomics has been retrospective, and unless somebody beats us, it'll be the first prospective demonstration. And one of the real hang-ups has been the turn-around time on genomic diagnostics.

Utah has a method where within 40 minutes, it can identify three of the major alleles [important to] warfarin dosing, [which] will determine about 50 percent of the variance in warfarin dose based on previous studies on warfarin.

So we believe that that's enough, and that we should give this a shot. We're doing modeling and simulation, and working with the FDA to see if we need to modify the trial. We're bringing in adaptive trial design, which is one of the things recommended in the Critical Path. We're probably going to be expanding it to other sites.

Right now, our power is to look at [International Normalized Ratio], and we'd like to be able to look at bleeding and complications and stroke and other clinical outcomes. So, that'll be our goal — to expand the trial beyond Utah.

But that's one of the things we know the agency wants to do. There are some cancer biomarker projects [for which] we are just beginning to form the teams to start to work.

In Imaging, we just had Ellen Feigal join us. Formerly at NCI, she's been at [the Translational Genomics Research Institute], but she's going to be on sabbatical from TGen, working with us on a cancer imaging project.

Jeffery Cossman — he was doing genomics of cancer in the 80s at the NCI. He's now left Gene Logic to join us to run our medical biomarker projects. So we're getting some really world-class people to join us to work on these biomarker projects. Jeff did some early biomarker work on lymphoma molecular typing.

What else are you working on?

We are working closely with Andy von Eschenbach at NCI on a cancer biomarker project that's going to be announced once we get the planning done. [Department of Health and Human Services] Secretary [Michael] Levitt is probably going to be announcing some more initiatives in this area.

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