All For One
Transcript of BioCentury This Week TV Episode 180
Dr. Francis Collins, Director, National Institutes of Health
Dr. William Chin, Executive Vice President of Science And Regulatory Affairs, PhRMA
David Wholley, Director, the Biomarkers Consortium, Foundation for National Institutes of Health
Sandra C. Raymond, President and CEO, Lupus Foundation of America
PRODUCTS, COMPANIES, INSTITUTIONS AND PEOPLE MENTIONED
The Food and Drug Administration
The National Football League
The Human Genome Project
Steve Usdin, Senior Editor
STEVE USDIN: Can a team of biopharma companies, NIH, and patient groups transform drug development? We'll ask NIH director Francis Collins and other key members of the Accelerating Medicines partnership. I'm Steve Usdin. Welcome to BioCentury This Week.
NARRATOR: Connecting patients, scientists, innovators, and policymakers to the future of medicine -- BioCentury This Week.
STEVE USDIN: Working separately, often in competitive secrecy, biopharma companies and governments spend billions hunting for biological targets for breakthrough medicines. Then companies invest time and money to develop drugs based on the same target. And all too often, after years of research, they all learn that a target that seemed promising was really a dead end. It's called duplication of futility.
In an effort to break this cycle, NIH, FDA, 10 drug companies, five nonprofits, and the Pharmaceutical Research and Manufacturers of America have created the Accelerating Medicines Partnership, or AMP. The idea is simple -- pool knowledge and resources to identify valid biological targets for drug development.
While academic corporate partnerships aren't new, AMP breaks new ground with its scale, putting patient groups, many companies, and government-funded university researchers on the front line against the duplication of futility. It'll be managed by the Foundation for NIH, a congressionally chartered nonprofit. And the results will be made public.
The partnership will start with Alzheimer's disease, type 2 diabetes, rheumatoid arthritis, and lupus. To discuss the Accelerating Medicines Partnership, I'm pleased to be joined by Francis Collins, director of the NIH, Bill Chin, executive vice president of the Pharmaceutical Research and Manufacturers of America, and David Wholley, Director of Research Partnerships at the Foundation for NIH.
Dr. Collins, in the press release that went out about the partnership, you said that the partnership was going to transform the way that drugs are developed. Can you explain? That's a pretty bold goal.
FRANCIS COLLINS: Well, it is a bold partnership. First of all, let's identify what the problem is that we're trying to solve. Here we are in 2014, after many decades of trying to understand how best to identify the right targets to develop drugs that are going to work against. And oftentimes, those don't turn out as well as one would like.
The failure rate in Phase II and Phase III clinical trials -- still over 50%. And so you've got all this way down a 14-year pipeline. You've spent hundreds of millions of dollars. And your drug actually just doesn't work for that disease, oftentimes because the inference that you used to pick that drug target was based on maybe a cell culture model or an animal model. And it just didn't turn out to work for the human disease.
So the good news is, we have this remarkable proliferation of new information about human biology, human disease, human genetics, all kinds of omics, imaging, other things. We ought to have a chance to do something fairly radical here, to put all that together and really identify those targets that are most likely to work. But it's a big task.
It's a thicket of information. You need a GPS to find your way to the right targets. No company is in a good position to do this by themselves. NIH would like to help with this, but we're not quite clear what the company initiatives would need to be. So we're getting together.
And this has not been done before. It's an unprecedented partnership -- 10 companies, the NIH, academic investigators. We are going to, in an open access fashion, try to see what we could learn from this proliferation of new data about how to place the right bets, bets on targets, which, if you then went on and developed a drug or a monoclonal or a biological, you had a much higher likelihood of success. That's the goal, so you don't end up with those awful failures at the end.
STEVE USDIN: So Bill, traditionally, pharmaceutical companies have been very secretive, closed places. You worked in the pharmaceutical industry yourself. Why have we gone now to this team approach, this collaboration of a pre-competitive space?
WILLIAM CHIN: Well Steve, as Francis has indicated, it still costs too much, takes too long to make medicines. And if the old method, secretive or otherwise, really continue to contribute to this state, we needed to do something else. And it had been sort of known that there was a possibility that if we all got together, we might be able to use our collective wisdom to be able to divine these new targets that you talked about, Francis, or even the biomarkers, David, that you'll talk about, that can help us with diseases.
So I think it's really a matter of an appreciation that we're at a point where we've got to do something different. We've got to do something bold, shall we say, that had not been done before, and that being secretive really didn't get the job done.
STEVE USDIN: So David, the FNIH's job is kind of to get these two sides together, because structurally, it's very difficult for industry and the NIH to sit down at the table and agree on these kind of things without some --
DAVID WHOLLEY: That's right, Steve. In fact, the Foundation for the NIH was formed specifically by an act of the US Congress to do exactly that, to bring together government entities, industry, patient organizations, and academic researchers to do the best possible science and support the mission of the NIH to advance human health. And so we do everything from global health programs that address malaria and malnutrition.
We work with the NIH and the National Football League on traumatic brain injury. We work on biomarkers with the FDA and the NIH. And now, the Accelerating Medicines Partnership.
STEVE USDIN: So very quickly, the NIH spends billions of dollars on diabetes, on these other targets that you're going to be looking at. Drug companies also invest billions of dollars in it. You're going to be spending much smaller amounts of money. How is it that what you're going to do is going to be something that isn't already being done?
FRANCIS COLLINS: Well, let's be clear what AMP aims to accomplish, in its first phase anyway, and these are pilots. We're focused on Alzheimer's disease, type 2 diabetes, rheumatoid arthritis, and lupus. Collectively, between industry and NIH, $230 million will be devoted to this over five years, just about equal contributions -- 50-50.
So both industry and NIH has skin in the game. Sure, that is a modest amount, to be sure, compared to what's being invested in these diseases. But also, keep in mind, what we're focused on is not the entire drug development pipeline. It is that first initial critical step of, are you picking the right target, and do you have the right marker to know you pick the right target? That's what we're doing.
It's a limited focus, but it's an area that's especially needy.
STEVE USDIN: Well, let's talk about that some more just in a moment, right when we come back.
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STEVE USDIN: We're discussing a partnership among NIH, biopharma companies, and patient groups with Francis Collins, Bill Chin, and David Wholley. Bill, one of the key ideas behind the AMP is this idea of a pre-competitive space. Can you talk about that?
What does it mean, and how did the pharma industry think about pre-competitive collaboration?
WILLIAM CHIN: So this pre-competitive effort is really part of a larger notion that there are collaborative partnerships that can be very effective. There are those who say that there's not such a thing as pre-competitive space, that anything that's valuable is competitive. But I think the way to look at it is that there is so much to understand about disease. You've talked about that, Francis.
And not one group will be able to do this on their own. I think each of these groups, whether it's government, industry, patient advocacy groups, are necessary, but not alone sufficient. So what we imagine is that getting together, you'll have wisdom of the crowd. You'll have efforts brought together to do things that won't duplicate each other.
There's a cost savings issue.
STEVE USDIN: So you don't have this kind of duplication of futility, where everybody goes after the same target and finds out 10 years later that it didn't work. David, one of the things I imagine that's important here is being able to draw the line between what's competitive and pre-competitive. How do you do that?
DAVID WHOLLEY: I think there's two aspects that. The first you've already touched on, which is, you need to find something that can be better done together than anyone working alone. If someone can do this better working alone, then they should do it working alone. You need that. It needs to be in that place in the Venn diagram, where the overlapping interests are there, and you truly bring all the scientists to the table and solve a problem.
The other thing is, I have seen, having been doing this now for eight, nine years, a really evolution from the industry prospective and what is considered pre-competitive. And it started out being everything. The products of the Human Genome Project were deemed to be competitive at one point.
But thanks to the efforts of the Human Genome Project and other partnerships, gradually the line has moved up the point where I think now industry is much more focused around the therapy, around the compound, rather than a lot of the more basic science that goes in front of there -- much more willing to share in that space.
STEVE USDIN: Dr. Collins, as part of it also, bringing the academic world along and making them realize it at least part of what they have to do has to fit in better with what industry's doing. So we're going to actually get therapies out the end of this.
FRANCIS COLLINS: I think so. I mean academics or most of them are very motivated to try to do something that's going to help people. That's how a lot of people got into biomedical research. But exactly how that path works out is not always so clear, if you're in a university.
The idea with this partnership with AMP that we will have the scientists from industry and from academia in the same room will keep the focus of our academic scientists on the steps that are most crucial, on developing and adhering to milestones, making sure we don't get distracted by science that's kind of interesting but wasn't really quite on the path that we were trying to get to, which is to identify those targets.
I think it's going to be a fascinating cultural experiment. I don't know that we've had these cultures mixed together in quite this kind of close proximity before. And it's going to be interesting and good for both.
WILLIAM CHIN: It's a very important point, because not only does NIH help to focus industry, but also patient advocacy groups. And I think that will lead to finding new targets, but also new markers that will help us with our entire development process.
STEVE USDIN: That's an interesting thing. We're going to talk about that later on the show, about the importance of patient groups in all of this. Very quickly, the list of partners that you've got from industry, they're all big pharma companies. A lot of the innovation in biomedicine is actually come from little biotechs.
Why aren't they part of it? Is there a way for them to get into this?
FRANCIS COLLINS: This is a pilot effort, and we hope other companies may very well get interested in joining going forward, including biotechs. The initial efforts were focused on companies who were willing to put money on the table. But keep in mind that a lot of what AMP going to do is competitive research. There will be RFAs and RFPs coming out of both the Foundation for NIH and of NIH.
Small companies that have the technology and the expertise may very well want to apply and get supported by this pot of money that's been generated to work on these diseases.
DAVID WHOLLEY: Remember also, the results are being made broadly available. So the biotech industry clearly gets --
STEVE USDIN: Everybody benefits. David, I imagine in an endeavor like this, one of the things that's really critical is the governance and getting that correct. That's FNIH's part. Can you explain a little bit about how it works?
DAVID WHOLLEY: Sure. So there's two pieces to this -- the strategic governance, which is, what areas are we going to look at, what are the general problems we're going to attack and how we're going to do it? I would say also monitoring the ongoing progress of things -- they have milestones built to them. We have goals that we have to meet -- are being done jointly with NIH and industry through these steering committees that are run through the Foundation for the NIH.
This is what we do. This is what we've been doing now for 10 to 15 years in managing these partnerships. There are a number of more tactical decisions around individual grants and so forth that are going to be made by the NIH within their granting process. And that is going to continue to be done the way that NIH has done it.
But the results will be brought back to these steering committees so that we make sure that we're on the right track. And I think it's also important to note that a lot of the early decision about how to do this, industry had some input into so that we make sure that the products of this are something that industry can actually use.
STEVE USDIN: Basically you're asking questions that matter to the companies that are trying to develop drugs?
FRANCIS COLLINS: Exactly. And that was critical in of the development of AMP. I'll be honest. I initially thought maybe we could just do all the diseases at once. Companies being talked about this said, come on, Collins, maybe that worked for the Genome Project. But here, we got to get specific.
And so the fact that we're focused on these initial set of diseases was very much because those are the ones that companies wanted to put down their bets on that felt that there was the greatest opportunity for progress and the greatest need.
STEVE USDIN: And one of the things that David mentioned, he talked about RFPs and contracts that are going to go out, and milestones. That's a different way of working than most academic groups are used to. That's more bringing in industry discipline to the academic world.
WILLIAM CHIN: Well, I think there is some activity of that sort already in place. But the industry input is really one of the key differences here, and input not just from one company, but several companies working together, which is also a new twist so that you create wisdom that is a result of several leaders in several companies, deciding that this would be of interest to all.
STEVE USDIN: We're going to be right back with Sandra Raymond, CEO of the Lupus Foundation of America. First, some facts about lupus.
NARRATOR: Now, back to BioCentury This Week.
STEVE USDIN: To discuss how the partnership could speed the creation of new drugs for lupus, we're joined now by Sandra Raymond of the Lupus Foundation, and continue our conversation with Francis Collins and Bill Chin. Sandra, just to start off, why lupus? Why is lupus an important target for a partnership like this?
SANDRA RAYMOND: In my estimation, it's the best target, because lupus is a complex autoimmune disease. We've had few targets. We have limited understanding of the disease. We have patients waiting for 10s of decades for new medications.
So it's really, really important.
STEVE USDIN: And Dr. Collins and Dr. Chin, can you tell us a little bit about, specifically focusing on lupus, what will the partnership do and what will it do that wouldn't have been done in its absence?
FRANCIS COLLINS: We have really a special opportunity now I think with lupus, with rheumatoid arthritis, which is an oftentimes overlapping condition. And both of those are a focus now for AMP. Because the immune system is really starting to be taken apart with a combination of cell-based technologies and genomics, which also gives you the chance to see what's happening in the immune cells that are active in a particular disease. The goal here, which is pretty bold, is to bring together science from both public and private sectors and look at individual immune cells -- not a clump of them all mixed together -- individual immune cells to see what are they reacting to, which ones of those are activated and are causing inflammation.
Which of those are trying to stop the inflammation but aren't quite succeeding to do so? To do this with human tissues, human data, human patients, whose phenotypes we can collect into this program. So it is really trying to deconstruct what it is that goes awry in the immune system to cause autoimmune diseases, with lupus being perhaps the most puzzling, most frustrating, most in need of a new therapy of all of them.
STEVE USDIN: And one of the things that I guess I wondered about this. Dr. Collins has made the scientific argument for what they're going to do. You make the argument for why this is important.
But beyond that, what's the role of a patient organization in AMP and in this collaboration?
SANDRA RAYMOND: Well, I think it's an important role, because I think really getting patient feedback and getting patient input is extremely important, especially in lupus. No one knows their body the way a lupus patient knows their body, because they haven't had good medications. So I think this is an opportunity for them to really express the kinds of things they're interested in terms of their quality of life.
BILL CHIN: Part of the complexity that we talk about is that we still don't understand how patients with the same disease might manifest symptoms of lupus in different ways. And so here's a great example of how patients will ultimately teach us about what to work on. And I think that's also a very important part.
SANDRA RAYMOND: The fact is that lupus affects the body in many, many different ways. It's a very heterogeneous disease, which is why clinical trials have failed. We had many, many failures in clinical trials in lupus. And we've had one drug approved in the last 60 years.
STEVE USDIN: And that wasn't for the most severe manifestations of it. What are the milestones, looking at the lupus work that partnerships can be doing?
FRANCIS COLLINS: Well, the lupus part of this is particularly technically challenging. The milestones for the first couple of years are to see, can we actually collect the necessary biological materials? Can we reduce to practice this very detailed look at genomics and proteomics of single immune cells in a human tissue that's involved in the disease?
And can we make sense out of that data in terms of teaching us something new about what's activated and what's not activated that causes this inflammatory process to go forward? This has not been tried before. This is right on the sort of leading edge of the possible.
And again, I think it's probably not something that would happen for several years, if it not for AMP pulling these experts together. And the hope is that out of that will come not only some really good basic science, which I'm sure will, but shine a light on areas in the network that the immune system uses that are actionable, that you can design a new kind of therapy that we haven't tried before that might be much more effective.
SANDRA RAYMOND: This is an integrated approach. We haven't had an integrated approach focused on lupus before.
BILL CHIN: The hypothesis here is that we have the tissue that actually is involved in the disease itself. And that allows us to use a model, a very successful one, of cancer, and developing drugs in cancer.
STEVE USDIN: We're going to talk more about that in just a moment, as we wrap up with Sandra Raymond, Francis Collins, and Bill Chin.
NARRATOR: Every month, BioCentury This Week will feature profiles in innovation, a special segment highlighting the stories of innovators whose work is improving lives and transforming the world of healthcare.
STEVE USDIN: We're back with Francis Collins, Bill Chin, and Sandra Raymond. Bill, you were finishing up there. You were talking about this idea of targeted therapies. One way to look at what AMP is doing is extending the success of targeted therapies in cancer to some of these other areas.
BILL CHIN: The reason why we've had recent success in developing better therapies for patients with cancer is the fact that we have access to the information that's embedded in the cancer itself, in the disease itself. And so in autoimmune diseases, we have the opportunity to pick out those white cells that are involved in the immune response and be able to study them as we've never been able to study them before.
And so I think that gives us a lever to be able to understand disease better and hence to create new therapies.
STEVE USDIN: So one of the things that skeptics of AMP are going to say is really, NIH's job is to do basic research. And what you're describing here is really the job of the pharmaceutical industry, which sold $40 billion worth of rheumatoid arthritis drugs last year. They should have enough money to invest in this. What would be your response to that?
FRANCIS COLLINS: I think it's both of our jobs to try to take the scientific opportunities that are in front of us and move them as quickly as possible towards clinical benefit for patients.
SANDRA RAYMOND: I think the answer is patients first.
FRANCIS COLLINS: Exactly. And if we have the opportunity to go faster by creating a tighter ecosystem here instead of having us off in separate corners, how could you go against that? NIH is going to be doing a lot of basic science, but we're not in the best position to know how to turn that into the next generation of drugs. That's what companies do.
Why do we have to stay apart? Maybe we could do this better together?
BILL CHIN: If there's anything we can do to keep patients from waiting another minute, another day, week, we should do it. And I think we have in our hands the ability to utilize our resources together. And I talk again about how getting minds together might be able to solve big problems in a more effective way than if individuals were involved.
STEVE USDIN: So you're starting out with three discrete areas. I know that there was some discussion early on that you were going to include schizophrenia, which is a tremendous area of unmet need. Why didn't that happen? And what might be some other areas that you might look at in the future? And can you get schizophrenia back in this?
FRANCIS COLLINS: I would love to get schizophrenia back in. It was one of the diseases that was initially focused on, where we had a whole design put together about how we would go after that. Ultimately, there was not a critical mass of companies that felt this was a high enough priority for them, that they were ready to sign up for that one. Without that kind of partnership, we didn't see we could include it an AMP.
NIH is continuing to do a number of the things that got talked about in that run up. And I certainly hope we'll be able to add schizophrenia in another year, as we see some success from this model.
STEVE USDIN: So to be clear, to get the companies to sign up means that they had to make an investment of about a million dollars a year per project. So they kind of had to put their money where their mouth was.
BILL CHIN: That's correct. And as in most early stages of transformation, there are some that are willing to take the steps a little bit faster. And so what we need to do is be successful here, provide examples of progress. And I think, we hope, right, Francis and Sandra, that this will serve as a model to apply to these diseases, that believe it or not, are even more difficult than lupus and diabetes.
SANDRA RAYMOND: The pharmaceutical companies in lupus have been very courageous with very few targets. So the reason for pharmaceuticals to get together on lupus is clear. They need those clearer targets, at least.
STEVE USDIN: Great. Thanks very much. That's this week's show. I'd like to thank my guests Francis Collins, Bill Chin, David Wholley, and Sandra Raymond. Have a thought about today's show? Remember, you can tweet about it using the hashtag #BioCenturyTV.
To read more about the Accelerating Medicines Partnership, log on to biocenturytv.com for my colleague Simone Fishburn's story. I'm Steve Usdin. I'll see you next week.