Print BCTV: 21st Century Cures Part 2 -- FDA's Woodcock, Pew's Coukell, Deerfield's Leff dissect the Path to Cures

21st Century Cures Part 2

Transcript of BioCentury This Week TV Episode 194



Dr. Janet Woodcock, Director, Center for Drug Evaluation and Research, FDA

Jonathan Leff, Partner at Deerfield Management and Chairman of the Deerfield Institute

Allan Coukell, Senior Director of Drugs and Medical Devices, The Pew Charitable Trusts



Rep. Fred Upton (R-Michigan)

Rep. Diana DeGette (D-Colorado)

Kathy Hudson, Deputy Director for Science, Outreach, and Policy, NIH

Frank Sasinowski, Director, Hyman Phelps & McNamara, P.C.

Dr. Sean Tunis, Founder, President and CEO of the Center for Medical Technology Policy


House Energy & Commerce Committee

President's Council of Advisors on Science and Technology

Patient-Centered Outcomes Research Institute

Friends of Cancer Research

Medtronic Inc.

Johnson & Johnson

National Institutes of Health

Centers for Disease Control



Steve Usdin, Senior Editor




STEVE USDIN: Does the path to 21st-century cures run through Washington? The House Energy and Commerce Committee says it does. Today we'll hear some of the advice the committee is receiving. 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: Last week, House Energy and Commerce Committee chair Fred Upton told BioCentury that it takes too long and costs too much to develop drugs.


FRED UPTON: Why is it that it takes 10 years a billion dollars get a normal drug approved? That ought to change.


STEVE USDIN: Representative Diana DeGette, who's partnering with Upton on the path to 21st-century cures initiative said FDA, NIH, and CDC are ripe for reorganization.


DIANA DEGETTE: I think we're going to be looking at the whole structure of these agencies to see how they work, how they can work better, smarter, how we can really keep that edge that we have.


STEVE USDIN: This week, in the second part of BioCentury's look at the path to 21st-century cures, FDA's top drug regulator, Janet Woodcock, provides her prescription. She says incentives for investment in modern manufacturing and a radical change in the way drugs are tested could get more new medicines to patients quicker and cheaper.


Jonathan Leff, a biotech investor and public policy analyst, says Congress should give drug companies longer monopolies on breakthrough drugs. Allan Coukell, who directs projects on drugs and medical devices at the Pew Charitable Trusts, says Congress should create a new approval system to streamline development of drugs for urgent unmet needs.


We're joined today by FDA's top drug regulator, Dr. Janet Woodcock, and by Jonathan Leff, chairman of the Deerfield Institute, and Allan Coukell, senior director for drugs and medical devices at the Pew Charitable Trusts. I want to start out with all of you. We're talking about what government can do to try to improve biomedical innovation. And one of the things that doesn't get put on the table a lot but I think is important is the idea of trying to get more manufacturing back in the United States.


Eighty percent of drug ingredients are manufactured overseas. Forty percent of the raw materials for drugs are manufactured overseas. And every day, there's something in the newspapers about some kind of horror of manufacturing problems overseas. Is that something that Congress and the FDA, the society should be working on?


DR. JANET WOODCOCK: Yes, I think there's some big opportunities. And we have faced vulnerabilities because of the sourcing of drugs now. There might be a shortage. There could be a natural disaster, and we actually don't have a source in the United States we can turn to for an essential medicine.


But now with new technology, drug manufacturing has an opportunity to become much more high tech and be made in a way much more like fine chemicals or foods in a continuous process. And this technology could come back to the United States, be a source of high-paying jobs, and also mitigate shortages, and be more flexible and agile than the kind of manufacturing we have now. But I think some incentives might be in order or some stimulation.


STEVE USDIN: So Jonathan, incentives, that's kind of up your alley. What kind of incentives, what is it you think that industry would need to invest in manufacturing bringing drug manufacturing back to the United States?


JONATHAN LEFF: Well, at the end of the day, I think from a manufacturer's point of view, the issue is cost and reliability of supply. And to the extent manufacturing has moved overseas, which clearly it has over the past several decades to a great degree, it's because of the cost equation and because overseas suppliers have been able to do it more cheaply and sufficiently reliably.


So if you want to reverse that cost equation, technology is, as Janet says, is one answer. Incentives may be another. I think we also need to make sure that there is a level playing field as far as the expectations for quality, which goes to making sure FDA has the resources to inspect overseas manufacturing facilities every bit as frequently and robustly as it does US facilities.


STEVE USDIN: And Allan, that's something you've looked into, isn't it?


ALLAN COUKELL: Yeah, it's an important area. Not only have we had really serious quality problems in recent years, both with domestic facilities. A lot of the quality problems that have led to the shortages of sterile injectables, but of course the drugs coming from India and China that people know about. So we have that, and then at the same time, we're starting to hear more and more from the industry.


As drugs get approved faster, they need to have clearance on their chemical manufacturing process. So it's a time to look at manufacturing, and as we move to a world of biosimilars and more complex molecules, there's a need for robust science around how do we characterize them? How do we evaluate small changes in manufacturing processes?


STEVE USDIN: And is this something, any of you, that there's some specifics that government really needs to do, or is it something that's just kind of obvious and industry will get it and start doing it on its own?


DR. JANET WOODCOCK: Well, I think there will be early adopters. There are now of things like continuous manufacturing. But it could move much faster because of the public need, including, I think, the breakthrough drugs. We're already seeing that breakthrough drugs that make a big difference to patients, there may be manufacturing problems that may cause shortages or difficulties in getting them out early.


So from a regulatory standpoint, we are trying to encourage this. We're forming the new Office of Pharmaceutical Quality at FDA to try to really facilitate new technologies and so forth. But there might be other things that could be done in advanced manufacturing.


STEVE USDIN: I want to switch gears a little bit and bring up something that I know Jonathan you've got an interest in. Were the Energy and Commerce Committee looking for specific incentives that they could have for encouraging biomedical innovation? And you've got something around exclusivity for small molecules.


JONATHAN LEFF: Well, yes, in fact, when you look at the kinds of things that Congress has done in the past that has been effective in stimulating investment in biomedical innovation, one thing is ensuring an appropriate period of exclusivity for sponsors to recoup these huge investments that they're making. So if you look at the Orphan Drug Act, which is provided for seven years of exclusivity, the GAIN Act, 10 years of exclusivity for certain antibiotics and 12 years of exclusivity for innovator biologics, all those things have helped.


When you look at small molecules, though, and go back to the original Hatch-Waxman legislation, five years of exclusivity was provided for innovator small molecule drugs. I believe and I think the economics clearly show that five years is not sufficient in most cases for an investment in developing a new chemical entity to be recouped.


STEVE USDIN: I want to get your ideas a little bit more about that and then get Allan and Janet's responses to that in just a moment. We'll be right back.




STEVE USDIN: We're discussing ideas for getting more better therapies to patients with Janet Woodcock, Jonathan Leff, and Allan Coukell. Jonathan, you were talking there about this idea of added exclusivity, which basically means giving a longer kind of monopoly period for drugs before they're subject to competition. What exactly are you thinking about?


JONATHAN LEFF: Right, well, if you go back to the origination of the Hatch-Waxman legislation, I don't think anyone anticipated at that time that we would get to a point where we are now where it costs over a billion dollars and takes 10 to 15 years to develop a drug. And when you come to recognize that, it's clear that five years of exclusivity is not sufficient to incentivize someone to make those investments. I think it was expected at the time that Hatch-Waxman was done that patent protection would provide for the exclusivity necessary to incentivize these investments.


STEVE USDIN: So how long do you think it should be?


JONATHAN LEFF: I think 12 years works. And this debate was had with biologics. The exact same math applies to small molecules. If you provided 12 years of data exclusivity, you'd create a level playing field for small molecules and biologics and incentivize investments.


STEVE USDIN: Well, it's interesting, because actually in the biologics debate, they were saying, no, the math is all different for biologics, and that's why they need a longer period. But Allan, do you think something like that would fly as Congress? Is the country in a mood to extend the monopoly period for drugs now?


ALLAN COUKELL: Well, there's a political question and a policy question there. And obviously the politics of 12 years of exclusivity on biologics continues to be controversial. I think reopening Hatch-Waxman carte blanche for all products would be difficult. As Jonathan has said, Congress has already done some tailoring for certain products, orphan products, antibiotics and so on.


But as we see the R&D productivity in the industry get worse and worse, the costs of bringing things to market rise and rise, I'm not sure that our principal focus should be on raising revenue on the back end as much as it should be on efforts to reduce development costs, reduce clinical-trial costs, and so on.


STEVE USDIN: And that's a good segue to what I wanted to ask Janet about. Because yes, so one way to look at it is to say, well, it costs a billion dollars and 10 years if those numbers are correct for developing a new drug, and so we should give the companies opportunities to recoup more of those costs. But another is to say, well, really aren't there ways to make it so it's cheaper and faster?


DR. JANET WOODCOCK: Well, sure, and the big problem is predictability. The success rate is still one in 10 out of clinical development. And that requires more work on the very front end, which I think is being started. However, I think that to reduce clinical-trial costs, which really have ballooned the cost of a development program over the last couple decades, is a reasonable thing to do. And it's achievable by creating clinical-trial networks and not doing a single trial for every stage of development for that drug.


STEVE USDIN: And can you explain a little bit? Because it came up in the round table for the Energy and Commerce Committee also, this idea of clinical-trial networks. And I don't think people really understood what you were talking about.


DR. JANET WOODCOCK: Well, you need to turn the paradigm on its head. Right now, a company will say they want to do an efficacy trial. They'll get a protocol together. They'll get thought leaders. They'll get PIs, investigators. Then they'll have to negotiate agreements with each university.


STEVE USDIN: And it all takes a couple of years.


DR. JANET WOODCOCK: Years, yeah, and then the trial may take years to accrue and so forth. And then at the end of the day, and time is money in this business. Whereas if you have a protocol already set up and you can plug a drug into it and it's already running, then it might only take a matter of a few months to get that drug to begin to be evaluated. So there's a huge saving in time. And also by sharing the infrastructure, the IT, the case report forms, all those things, you can save a lot of money.


STEVE USDIN: And is that, again, looking at things that the government can do and should do, are there things that the FDA, that Congress could or should do to encourage the development of those kinds of networks?


DR. JANET WOODCOCK: We've been encouraging it, as you know. And there are some standing up in cancer and some running in cancer. But I think it's possible that various activities could be done to encourage this more broadly.


STEVE USDIN: And Jonathan, Allan, do you think that's something again where there could be concrete action rather than seeing a couple of pilots that are up and running now, where it might be something that that would be the standard mode of operation?


JONATHAN LEFF: I think that's what we need to try and move to. And as Janet alluded to, there's a Lung Cancer Master Protocol, which is being developed by Friends of Cancer Research as a model for how to do this. And there have been others, including the I-SPY initiatives. Right now, it feels like more of the experiment, and the norm is still the traditional, old-fashioned, high-cost way of developing drugs. We need to find ways to move the experiment into the norm.


ALLAN COUKELL: I'd like to talk about a trial that was an interventional cardiology trial conducted in Scandinavia. It enrolled 7,000 patients, followed all of them to the end, and it cost $300,000. If we did that trial in the US the traditional way, it would probably cost $30 million. So the potential to really transform R&D is just huge. Why could they do that that way in Scandinavia?


STEVE USDIN: Let's talk about that right back from another break.


FRANK SASINOWSKI: My first proposal is for FDA to adopt a practice of considering the appropriateness of accelerated approval for each new therapy. Both PCAST and FDASIA exhort FDA to use its accelerated approval authority more.




NARRATOR: Back to BioCentury This Week.


STEVE USDIN: We're continuing the discussion about the path to 21st century cures. Allan, you were talking about this fantastic study from Sweden, something like the IKEA approach to clinical-trials. What was it, and how did they do it, and could something like that be done here?


ALLAN COUKELL: It was called the TASTE trial, and it was built on an existing registry called the Sweet Heart Registry, which collects outcomes on patients who undergo cardiovascular procedures. So everyone who gets a stent in Sweden goes into this registry.


And so when they randomized people to one treatment or the other, they were just able to pull that data out. So it was a much more efficient, less expensive way of running a trial, in some ways much like the clinical-trial networks we were talking about a minute ago.


STEVE USDIN: So you can do that in a place like Sweden where you have good electronic medical records, a single payer, a population that doesn't move around a whole lot. Can you do something like that here?


DR. JANET WOODCOCK: I think so. It's just going to take more effort and work. But the networks are being set up, say, by PCORI, the PCORnet, and other efforts that are going on with the electronic health record eventually would get us there. But I don't know whether we have enough time to wait. We really need to make an overt effort to get this done.


STEVE USDIN: So is that again something where the Energy and Commerce Committee is looking for things that they can do that are going to advance biomedical research, that there's some either government investment or some kind of regulations that are needed to move this forward?


DR. JANET WOODCOCK: I think some thought has to go into that, but clearly we need a more efficient way of generating evidence about how to treat people.


STEVE USDIN: Allan, I want to switch gears onto another topic. And this is something that also has come up in the context of Energy and Commerce Committee's discussions. It's something called special medical use. It's got another name, limited population something or other, LPAD. What is it? What do you think about it?


ALLAN COUKELL: So this is the idea that was put forward a couple of years ago and has subsequently been developed by the many people, including us, and Dr. Woodcock, and the President's Council on Science and Technology. But it says, often you might want to approve a drug for a limited population. And in that limited population, they might have a risk benefit profile that's different from the general population.


So how do you say, and for that population to take antibiotics, if you have people who can't be treated with existing drugs, they have a different risk benefit profile than everyone who could already be treated with penicillin or whatever. So you might accept different or more limited data for those patients and get that drug to market quicker and more efficiently to meet that unmet need.


But you want to send a strong signal to prescribers and providers that it hasn't been evaluated in the general population. So there's existing bipartisan legislation called ADAPT that would do this for antibiotics, that would create limited-population antibacterial drugs, which would be both good for innovators but also help to address this public-health need of antibiotics.


STEVE USDIN: So, Jonathan, is that something that the investment community do you think would support?


JONATHAN LEFF: Yes, I think it's a very important idea and has a lot of potential to do what we've all been trying to do for a number of years now, which is find ways to reduce the time and cost of development. And one of the ways to get there, we've all found, and a major theme in the user fee re-authorization, the FDASIA legislation a couple years ago, was regulatory flexibility, giving the regulators the tools to be able to design approval paths that are appropriate to each specific drug in light of the population that it's designed to serve.


And FDA asked for and received the breakthrough therapies designation as an additional tool to work with really to get at this issue of tailoring the pathway to the opportunity, to the need. One other thing now that FDA has asked for is this tool of being able to use this limited-use population kind of pathway or designation to achieve the same goal of getting the right drug development.


STEVE USDIN: And Janet, we've just got a minute left, but the thing that's been holding this up is the concern, especially from some of the large pharmaceutical companies, that FDA is going to be involved in dictating the practice of medicine, and that this would become the norm, and that it would really be a disincentive for them. What's your response to that?


DR. JANET WOODCOCK: Well, there are always trade-offs, and people are worried. But the CDC recently said that 50% of antibiotics prescriptions right now are still inappropriate or they're not the best prescription. We want to avoid that going forward or are not going to be able to approve drugs that actually remain effective against resistant organisms. So I think this makes a lot of sense, and I don't think that we would use it unwisely.


STEVE USDIN: And you have mentioned antibiotics. Are you thinking now of limiting it to antibiotics or having it more broad?


DR. JANET WOODCOCK: Well, I think there are multiple populations it could benefit, and it's really going to be up to Congress on how they want to enact.


STEVE USDIN: Dr. Woodcock, one of the things that you've spoken about at other public forums is this idea that the progress that we're making in medicine today, especially in cancer, for example, is not enough, that we need to do more to be driving toward real cures or lasting remission. What do you mean by that, and what we need to do to get there?


DR. JANET WOODCOCK: Well, I strongly believe that. I think that we've made a lot of progress now in getting drugs that actually work in a targeted population and have a large treatment effect. But we get relapses from most of these targeted therapies because there's a population of cells, say, that emerge. So for adding real value to patients and real value to healthcare, we need drugs or a treatment regimen that gets people either in remission or actually cures solid tumors.


STEVE USDIN: And that's presumably going to require combinations of targeted therapies. Allan, one of the things I mentioned, payers, when they hear that, they're going to start screaming for the exits, because you're talking about piling on costs of one expensive drug on top of another expensive drug.


ALLAN COUKELL: We are at a challenging time when the scientific potential is great and where the healthcare system is straining to incorporate the costs now. So we are, I think, as a nation going to have to think very carefully about clinical value and what we're willing to pay for it. And that's a conversation that is, I think, just getting going.


STEVE USDIN: And how can that conversation advance, and how can it advance to action that's going to lead in a good direction, basically that's going to get people the drugs that they need, both existing ones and creating new drugs?


ALLAN COUKELL: Well, to overstate a little, I think, and not just in drugs, but in general in healthcare, we have historically paid for whatever came along. And we're going to have to be more discriminating and say, this is a clear advance because we have data to show that it's a clear advance. And therefore we'll use it and pay for it.


STEVE USDIN: And part of what Janet was talking about, though, is saying you have to take steps. It's incremental. And something that may not seem like a big step at first, but if you don't reward that and have it, then you're not going to get to those big steps. Jonathan, what does it look like from where you sit?


JONATHAN LEFF: Well, I think looking at this issue as an economic equation, what we really want to do is incentivize the investments that turn the science into treatments that can be transformative and have the biggest impact on the biggest medical needs out there. So how do we do that?


Well, one thing that we've done and I think made a real impact on over the last several years is designing these regulatory pathways that are focused and more efficient for drugs that are breakthroughs and serve major unmet needs, reducing the time and cost of developing those drugs.


STEVE USDIN: We're going to come back in just a moment, wrap up with Janet Woodcock, Jonathan Leff, and Allan Coukell.


DR. SEAN TUNIS: So at the same time as we're hoping to introduce new drugs into the healthcare system with less information about safety and efficacy, we're also putting pressure on payers, and providers, and health systems to demand more evidence of comparative effectiveness and value in order to be able to deliver high-quality and efficient care.




STEVE USDIN: We're wrapping up with Janet Woodcock, Jonathan Leff, and Allan Coukell. To all of you, one other topic that I wanted to bring up is the idea of transparency. And it's an area where Europe seems to be taking a very divergent path from the United States in making the regulatory system much more transparent than the United States. Is that something that we should think about here, that Congress should think about?


DR. JANET WOODCOCK: You're looking at me. I mean, I think there are two different issues here. One is the clinical-trial data. And we believe at the FDA that really the release of the data should be in the hands of those who conduct the trial or are responsible for the trial.


If we were additionally responsible for managing a very large inventory of clinical-trial data and responding to thousands of questions and so forth, I think that would be very difficult on top of our other duties. And really, it's not our data. So I have always believed and I've testified I think that clinical-trial data should be made available, publicly.


STEVE USDIN: But you're not sure the FDA should be the one to do it.


DR. JANET WOODCOCK: I'm sure that we shouldn't.


STEVE USDIN: Jonathan.


JONATHAN LEFF: Well, I think this is a very important issue, and it all gets to the question of how we can make drug development better and how we can avoid spending a lot of money and treating a lot of patients with ineffective drugs to learn the same lessons over and over again. And secrecy creates the risk that that happens and does happen.


One idea that I have I guess to this issue of transparency is that the greatest repository of clinical-data information in the world today lives somewhere at FDA, and it's in the form of all of the submissions that companies make about their results, and the feedback that they get from FDA, and all the correspondence. All of that exists. FDA cannot share that under current statute.


This is something that Energy and Commerce Committee could look at and Congress could change and essentially turn the paradigm on its head. Right now, the paradigm is all of that information is deemed to be commercially confidential information unless someone can prove otherwise. What if we turn it on its head and said, let's deem it to be information that's in the public interest to share?


And FDA could just post each of these documents on a PDF on their website unless someone can demonstrate that there is a commercially confidential aspect to it that needs to be redacted. If we turn that on its head, I think we could release -- and I'm not talking here about patient-level data, but about all the summary, analysis, clinical-trial reports, and discussion among sponsors and the FDA about clinical data, not manufacturing and CMC.


STEVE USDIN: I can tell Janet wants to jump in, but I want to give Allan a chance first.


ALLAN COUKELL: Yeah, you talked about the moves in Europe, and there are also some important steps in the US. Medtronic not long ago made its patient-level clinical data for one particular product available to be re-analyzed by outside groups. Johnson & Johnson has subsequently committed to doing the same thing for their entire database of clinical-trials.


So I think companies -- and then you see in public-private partnerships and so on companies recognizing the value of sharing information. So exactly what the model is I don't know. But clearly there is movement.


STEVE USDIN: Few seconds left.


DR. JANET WOODCOCK: Sure, well, again, I agree with the clinical-trial data release under certain circumstances. But I think it needs to be done by the data holders, because there are a lot of privacy issues. There are a lot of issues that have to be dealt with. As far as a transactional data, I also believe that we would benefit by having more openness.


STEVE USDIN: That's all the time that we've got today. I'd like to thank my guests, Janet Woodcock, Jonathan Leff, and Allan Coukell. Remember to share your thoughts about today's show on Twitter. Join the conversation by using the hashtag #BioCenturyTV. I'm Steve Usdin. Thanks for watching.