Print BCTV: Right to Try -- Right-to-try legislation allowing early access toexperimental drugs

Right to Try

Transcript of BioCentury This Week TV Episode 195




Lucy Caldwell, Communications Director of the Goldwater Institute

Diane Dorman, Vice President for Public Policy at the National Organization for Rare Disorders (NORD)

Sjaak Vink, CEO of myTomorrows




Richard Klein, Director, Office of Special Health Issues, FDA

Margaret Hamburg, Commissioner, FDA

National Institutes of Health

Francis Collins, Director, NIH

Neuralstem Inc. (NYSE-M:CUR)

Google Inc. (NASDAQ: GOOG)



Steve Usdin, Senior Editor




STEVE USDIN: Several states have recently passed laws giving patients with terminal illnesses the right to try unapproved, experimental drugs. Are they good for patients and society? We'll hear from proponents and skeptics. And we'll talk to a European company that's serving as a middleman between patients drug developers. 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: Legislatures in Colorado and Louisiana have quietly launched the right-to-try movement, giving terminally-ill patients the right to try experimental drugs that have not been approved by FDA. Other states are preparing to follow their lead. The laws are meant for patients with terminal illnesses who can't be helped by approved therapies. They apply to drugs that have gone through a Phase I trial, a small safety study in healthy volunteers. If the manufacturer agrees, the experimental drugs are provided outside a clinical trial.


Supporters say Right-to-Try promotes the most basic human right, to preserve one's own life. They say patients with terminal illnesses have run out of options, should be allowed to take enormous risks. They point to cases when access to an unapproved drug saved or extended a life and the cases when denying access removed all hope.


Opponents say it's dangerous and disingenuous to ignore the vast majority of drugs that fail after Phase I. They argue the right-to-try laws provide false hope and could expose vulnerable people to dangerous, ineffective drugs. They're also worried that Right to Try will undermine the development of life-saving drugs, because patients will refuse to sign up for clinical trials.


FDA hasn't taken a position on state right-to-try laws. But in a statement to BioCentury this week, it said "the drug approval process represents the best way to assure the development of safe and effective new medicines for patients".


State right-to-try laws are based on a proposal drafted by the Goldwater Institute, a libertarian think tank. To discuss the right-to-try movement, I'm pleased to welcome Lucy Caldwell, who's joining us from the Goldwater Institute in Phoenix.


Lucy, to start with, can you tell us what is Right to Try and what's going to be accomplished by this legislation?


LUCY CALDWELL: Thanks for having me. The Goldwater Institute designed the Right-to-Try Act because there are over a million Americans dying every year of terminal illness. And there are many drugs that could be lifesaving, but they're locked out of the process to access them.


The Right-to-Try Act is going to change all that. It's going to fix the broken system by allowing terminally ill patients, with their doctors, to gain access to experimental treatments that could save their lives.


STEVE USDIN: How is it going to be different? My understanding is that the state right-to-try laws give patients the right to access drugs if companies agree to it. What FDA said, what Richard Klein from the FDA said on this show a few weeks ago, is that whenever companies -- virtually always when companies go to FDA and ask for permission to give access to experimental drugs -- the agency almost always says yes. So why is there a need for this? What's going to be different?


LUCY CALDWELL: The FDA may be saying that. But many drug companies are singing a different tune. They have told us-- and I don't want to give specific names of drug companies, because they're fearful of the FDA within this process. But many drug companies have said that they want to get these products to patients earlier. And why wouldn't they? But realistically, behind the scenes -- because of this decade plus, billion dollar drug approval process -- it's very hard to get the FDA to be cooperative when they're trying to get drugs to patients.


STEVE USDIN: So one of the other things that people are concerned about is that drugs having been fully tested after Phase I trials. That a lot of drugs -- that safety problems come up later in Phase II and Phase III. And certainly efficacy hasn't been demonstrated after Phase I. And that the Right-to-Try movement is likely to expose patients to drugs that either aren't safe or aren't effective. What would be your response to that?


LUCY CALDWELL: Well, Phase I does determine safety. After Phase I, which occurs in the first few years of a drug's trial process-- which remember, is after years and years of R&D -- we do know whether a drug poses an immediate danger to someone. And remember what patient pool we're talking about. We're talking about terminally-ill patients. We're not talking about people having elective procedures.


You're right. We cannot guarantee what side effects will or will not occur under one of these drugs. But there's a side effect that I can guarantee you if they don't get the drug, and that's death.


STEVE USDIN: So there are several states that have already passed these laws now. Do you know of any companies that are actually willing to provide drugs, access to experimental drugs on the basis of these right-to-try laws?


LUCY CALDWELL: Well remember, this law has only been in effect for a couple of weeks. But already, we're seeing drug companies that are quickly mobilizing to navigate the process. One company, called Neuralstem, is working on getting out to Colorado -- the first state that passed the right-to-try law -- in order to perform their cutting edge, experimental treatment to cure ALS on patients there.


That drug? That drug has an 85% efficacy rate in trials. Whereas there are patients who, without the drug, are guaranteed to die from ALS. So we're seeing that drug companies, many of them are eager to get patients access to these drugs. And I think we're going to see that later this summer.


STEVE USDIN: Do you think that companies will and should have the right to charge, to make profits from drugs that are provided on the basis of right-to-try laws?


LUCY CALDWELL: The Right-to-Try Act doesn't address costs. It puts patients first. It's basic. It says the problem here is a lack of access to these experimental medicines for patients who need them right now. So the bill does not get bogged down in addressing cost issues. That will be left up to the individual companies and patients. It's about cutting the red tape, cutting the regulatory maze around questions like cost, insurance, stuff like that. And just asserting that patients should get access, no matter what.


STEVE USDIN: Do you have a concern that Right to Try and giving patients access to experimental drugs could undermine clinical trials of -- patients will say, well, why should I go in a clinical trial and risk being randomized to either placebo or standard of care, when I can just access the drug directly?


LUCY CALDWELL: Certainly Right to Try does have the potential to really revolutionize how we treat the drug approval process in this country generally. When people say, this could mess up clinical trials, well, the clinical trial process itself is an outdated system. The FDA commissioner, Peggy Hamburg, herself recently said we are currently using 20th century methods to address 21st century science. And that's absolutely right.


Instead of asking whether Right to Try is going to negatively impact our backward, double-blind clinical trial process, what we should be asking is why we have a double-blind clinical trial process in this country that locks dying patients out of drugs for a decade plus? So it may impact the clinical trial process. But everything we know about genomics, everything we know about individual biology, everything we know about how to gauge a drug's efficacy and safety very quickly -- let's work on changing our process. And that's what the "Right to Try" Act is going to do.


STEVE USDIN: Well, so are you suggesting that giving patients access to drugs that have only had Phase I trial somehow is going to generate the data that's going to be necessary to determine whether they're safe and effective?


LUCY CALDWELL: Well, the Right-To-Try Act, every state -- this is the beauty of a state-level reform. Every state is able to tailor the legislation to serve their residents best. So in several states that have passed the Right-to-Try Act, they do address the need. That there may be an ongoing need for companies to use data from the right-to-try patients, if they see fit. And they will certainly be able to do that.


It's up to the companies. And the companies certainly have an interest in getting their drug approved fully for market. That doesn't go away under Right to Try, because a drug must be in an ongoing clinical trial to even be eligible. So I don't think that we should have any fear about what data will be available. I think there's going to be scads of it. More than now.


STEVE USDIN: Well, thanks very much, Lucy Caldwell with the Goldwater Institute.


We'll continue the discussion in a moment with a patient advocacy group's perspective. First, right-to-try advocates want to open access to drugs after Phase I safety trials. Success in Phase I isn't always a good predictor of final approval. Here are the numbers.




STEVE USDIN: To continue the discussion about the right-to-try movement, I'm now joined by Diane Dorman, Vice President for Public Policy at NORD, the National Organization for Rare Disorders. So Diane, this idea of being able to give patients access to drugs right after Phase I testing, do you think that's a good idea?


DIANE DORMAN: I think it's really unsafe. Because in Phase I, they're trying to prove safety, but in very small populations of individuals who are not affected by the rare disease, or any type of disease. So we would have some sort of concern about that.


STEVE USDIN: So let's go a little bit further on that. Because people think that, and what Lucy Caldwell said is, basically you know about the safety of a drug after a Phase I trial, which is conducted in a small number of healthy individuals. What is your feeling about that?


DIANE DORMAN: I really think that they should be taking it into Phase II, and in in-patient populations that are affected by this particular condition, to see if it actually works. Because we want to make sure that the clinical trials are conducted in an efficient and as speedily as possible, to get these therapies to the patients, to wider populations, as quickly as possible.


STEVE USDIN: So what Lucy Caldwell also argued is that randomized clinical trials take too long, and patients can't wait. And they should just be able to have access to these drugs, and we'll find out about efficacy further on down the road. What's your sense of that?


DIANE DORMAN: I don't know if many patients would be willing to do that. Because within the rare-disease community, there are many patients who not only want safe products, they also want effective products. Because there are so few therapies available for these rare diseases. So ensuring that they're not only safe, but effective, is critically important.


STEVE USDIN: And one of the other issues about Right to Try is whether companies should have the ability to profit from experimental drugs, and whether they should be able to market them. What are your thoughts about that?


DIANE DORMAN: The FDA came out with a guidance on that back in 2009, I believe. And giving some guidance to companies, should they decide what they need to-- because, for whatever circumstances-- would need to charge, maybe just recoup the cost the actual clinical trials itself. But to make a profit on something would be a real concern. But recouping the costs is a possibility. But I don't know of any companies, at this point, that have ever done that. So I really can't respond directly as-- maybe speaking with the company about that.


STEVE USDIN: And the other thing that seems to be getting set up here, maybe the potential for it, is for each state to have different laws about what patients can access. What kind of experimental drugs they can access, what the terms of it are. And setting up the states as the regulatory body, rather than the federal government. What are your thoughts about that?


DIANE DORMAN: That would be circumventing a process that started a long time ago at the FDA. That's why we have an FDA, to review the data on these clinical trials to ensure that they're not only safe but effective. And that, in some way, could circumvent an entire agency.


STEVE USDIN: And the proponents of this would say that's a good thing. Their feeling is that FDA isn't doing the job that it should, and people aren't getting access to drugs. So let's just go around them.


DIANE DORMAN: Yeah, I suppose so. But that doesn't mean that the majority of people really want a product that actually works. Because if they're accessing a therapy, and they're going through their insurance companies -- I would have some concerns, if I was an insurer, to say it's experimental, therefore we're not going to pay for it.


So there, you'd have some people who could afford to pay for it out-of-pocket themselves. And for all those other people with this particular condition, whatever it might be, would not be able to afford it. It would kind of create a two-tier healthcare system of those who can afford and those who cannot.


STEVE USDIN: And the other thing I'm wondering is, does it also set people up to be exposed to basically ineffective, quack remedies? I mean the United States has gone through waves of these. For example with Laetrile, made out of apricot pits or something like that. Is that likely to happen if these right-to-try laws persist?


DIANE DORMAN: That's a possibility. I mean, for the rare disease community, it can take so many years to even just reach a diagnosis. So reaching out, trying to figure out a therapy that might work for them, is critically important. And talking with some of the patient groups, they have gone from snake oil salesmen to quack and to others, just trying to find something that relieves them of their system. So that would be a concern.


STEVE USDIN: Diane, the right-to-try laws are a reaction to a sense that patients don't get access to experimental drugs as quickly and as easily as they should. Do you think that there are things other than right-to-try laws they can and should be done to improve access to experimental drugs?


DIANE DORMAN: There is one possibility. We know that the FDA does approve these requests within 24 to 72 hours, normally. And then because it is experimental, informed consent is required. Therefore IRB review is required as well. And that particular system could be reviewed, in order to shorten the time that a patient could get access to it, should the company decide to provide that particular therapy to them.


Because for some IRBs, they may only meet every month, once a month or two months. And each of the people on the IRB have to vote. Is there a way to change that system just a little bit? Have a central IRB, or an IRB of record, who would review this, so it's not going to maybe a university or medical center, but in one central place? That might be an opportunity to shorten the time to get access.


STEVE USDIN: And the IRB, these are the institutional review boards that make a decision about whether it's ethical and safe for patients to get access to drugs and experimental drugs.


DIANE DORMAN: That's correct.


STEVE USDIN: And so, is there anything else? The bigger part of this all, of course, is that patients aren't getting drugs as -- drugs aren't being developed as quickly as people would like them to. Do you have ideas, going into the system, of other things that could be done to get drugs, especially for rare diseases, out to patients more quickly?


DIANE DORMAN: I think looking at the clinical trial process is something that we're looking at. We do know that there had been products approved and gotten to the patients coming out of Phase II, or out of Phase I, when the efficacy is very obvious. So there may be an opportunity to look at the clinical trial process, especially for small patient populations, and to see how that system can be changed a little bit to get those products to patients much sooner.


And also, not only working with the FDA, but working with the National Institutes of Health. Which NCATS, and the TRND program. They could be a way to help companies shorten the amount of time for clinical trials. Francis Collins talks many times about the value of death. So is there a way to marry the operations of those two agencies in a more efficient way to do that?


STEVE USDIN: OK, great. Well, thank you very much, Diane. Next, we're going to speak with the CEO of a Dutch company that has a unique approach to compassionate access. First, the right-to-try movement's response to the time it takes to develop drugs. Here are the numbers.




NARRATOR: Now, back to BioCentury This Week.


STEVE USDIN: We're talking today about access to experimental medicines. I'm pleased to be joined by Dr. Sjaak Vink, CEO of myTomorrows, a European company that acts as an intermediary between patients and companies that are developing experimental drugs. Dr. Vink, can you tell us what myTomorrows is doing, and how it's different from the idea of providing broad access to basically to anything?


SJAAK VINK: We are an online marketplace focusing on life threatening and debilitating diseases. So in oncology or central neuro or rare diseases. And we are using the legislation regulations of the compassionate use, or early access, around the countries that we work in to organize early access for the patients and physicians who are really in need and have run out of treatment options.


STEVE USDIN: So can you give an example of the kinds of drugs that you give access to? And also you mentioned in the countries that you work in, what countries do you work in?


SJAAK VINK: We work all over Europe. We started in the Netherlands, because we think the next to individual freedom to choose for a patient and a physician. At the same time, the patient privacy is very important. The Netherlands is known being more or less the Switzerland with regard to data. So it was very good point to start. We thought, well if we start in the Netherlands, and we could do it there in such a way that we take care of the patient privacy very well, then we could do it everywhere. And we've now been reaching out all over Europe, and even outside of Europe, for several countries.


STEVE USDIN: So what kind of relationships do you have with drug companies? What kinds of drugs do you make available? Is it just any kind of drug? Or do you have some kind of vetting process? How does that work?


SJAAK VINK: Yeah, well. Of course, it's a search and select procedure. But at the end, we are an independent marketplace. And at the end, every innovative drug company or biotech company could come to us and see whether the search and selection procedure could be done in a proper way. And if so, they are allowed to get onto that online market.


STEVE USDIN: And so patients and physicians can look at your website and try to find experimental drugs that might help them?


SJAAK VINK: That's right.


STEVE USDIN: And in Europe then, are companies allowed to charge for those drugs? Are they allowed to promote them?


SJAAK VINK: It differs by country, but in most of the countries they are allowed to charge for the drugs, they are not allowed to promote it. Neither are we. What we promote is that we have additional options for patients and for physicians that have run out of treatment options.


So we are telling them -- you were asking what kind of drugs do we have -- for example, we have for renal cancer, we have drugs available. You know that the patient empowers himself very much by Google, et cetera, nowadays. So patient searches a Google on renal cancer, because he was told that he had run out of treatment options, for the standard of care options. And he finds myTomorrows, he can go to myTomorrows website and search for the renal cancer and can find one or two options. And then he can discuss with his physician.


STEVE USDIN: Great. Well, we're going to talk about myTomorrows, and your approach, and especially the business that you've got in just a moment, when we come back. BioCentury's been reporting extensively on debates over compassionate access to experimental drugs. Our complete coverage is available online. More with Sjaak Vink in just a moment.




STEVE USDIN: We're wrapping up our discussion of accessing experimental drugs with Sjaak Vink, CEO of myTomorrows. Dr. Vink, your company, it's a business. Can you tell us what your business model is? How do you make money?


SJAAK VINK: Yeah. It's a business. But it's a social entrepreneurship. We think entrepreneurship is very important. We think with entrepreneurship you can achieve greater goals then you can if you're not-for-profit. Although, having said that, we think it's very important that the business model that you choose forces you to really focus on what's needed in society as a whole.


For that reason, we will be charging a fee for a patient, or for the system, that's a not-for-profit fee, as long as treatment is not yet approved for the market. As soon as it's approved for the market, then we will charge the company involved for a small royalty.


STEVE USDIN: You say a small royalty. Can you give an idea of --


SJAAK VINK: Single digits.


STEVE USDIN: Single-digits royalty?


SJAAK VINK: Single-digits royalty, yeah.


STEVE USDIN: And why would companies agree to that? What are they getting out of this?


SJAAK VINK: Well, if you take a look at what have been the registrations of last couple of years at the FDA, then you can conclude that most -- I think even 80% -- of the new drugs are coming, at the end, from innovative companies that are small companies, small biotech or pharma companies.


During the process of clinical studies, at a certain moment they're forced to sell either the product or the whole company to big pharma companies, because they cannot afford to go on anymore. We think it's very important for those small companies that have a lot of innovation and entrepreneurship in itself, that those stay independent. And they are willing to pay a small digit --


STEVE USDIN: But how does working with myTomorrows help those companies to stay independent?


SJAAK VINK: Well that's easy. They will have early income, because it's allowed in most of the country to charge the patient or the system for the innovative, experimental drug. And at the same time, they will have real live data. And those real live data will help speed up the system and create a strong pathway toward market approval.


STEVE USDIN: So that begs two questions. One is, are you going to actually generate enough volume so that it's going to make a difference in the life of these small companies? And the second is, is the data that's going to come from expanded access, outside of a clinical trial, going to be sufficient to get regulatory approvals?


SJAAK VINK: On both of the questions, the answer is no. No, there's not enough money from early income to make it possible for the company to stay independent. But it will be easier to get venture capitalist money. Because if venture capitalists see that there's early created now already, it's very attractive for them. So that's the answer on the first question.


The second question, no, it will never be that real life data, in itself, will be enough to get market approval. It will always be a combination of the clinical study data and the real life data. But it will absolutely be added value.


STEVE USDIN: We've only got a few seconds. Very quickly -- you're operating in Europe now? Any plans for coming to the United States?


SJAAK VINK: Absolutely. This is the country with the Statue of Liberty, we have to be here.


STEVE USDIN: And do you need changes in regulations, laws, to be able to operate here?


SJAAK VINK: Well, what's very important, what we find out in the other countries, is the attitude of the regulator.


STEVE USDIN: Great. Well, thanks very much. That's our discussion for this week. I'd like to thank my guests, Lucy Caldwell, Diane Dorman, and Sjaak Vink. Have a thought about today's show? Remember you can tweet about it using the hashtag #biocenturytv. I'm Steve Usdin. I'll see you next week.