Print BCTV: Type I Diabetes -- How TrialNet consortium aims to prevent, delay and reverse Type 1 diabetes

Type I Diabetes

Transcript of BioCentury This Week TV Episode 168

 

GUESTS

Dr. Ellen Leschek, Program Director, Type 1 Diabetes Trialnet, NIDDK, NIH

Dr. Lisa Spain, Program Director for Immunobiology of Type 1 Diabetes And Autoimmune Endocrine Diseases, NIDDK, NIH

Cynthia Rice, Senior Vice President, Advocacy and Policy, Juvenile Diabetes Research Foundation

David Nexon, Senior Executive Vice President, Advamed

 

PRODUCTS, COMPANIES, INSTITUTIONS AND PEOPLE MENTIONED

abatacept

Orencia

The Artificial Pancreas Project

University of Virginia

Teplizumab

Food & Drug Administration

Centers for Medicare and Medicaid Services

 

HOST

Steve Usdin, Senior Editor

 

SEGMENT 1

 

STEVE USDIN: Can type I diabetes be prevented or delayed? We'll speak with scientists who are testing tens of thousands of people to find out. And in our Affordable Care Update, what does Obamacare mean for patients with chronic diseases like type I diabetes? I'm Steve Usdin. Welcome to BioCentury This Week.

 

NARRATOR: Your trusted source for biotechnology information and analysis -- BioCentury This Week.

 

STEVE USDIN: Type I diabetes is a life-threatening disease often strikes children. Type I diabetics face a lifelong struggle, as the patient's own body slowly destroys its insulin-producing cells. Unlike type 2 diabetes, type 1 cannot be prevented with lifestyle changes like diet and exercise. Type 1 patients can only test their blood frequently and inject themselves with insulin.

 

But researchers hope it may be possible to use drugs to prevent, delay, and even reverse the progression of type 1 diabetes. NIH and diabetes patient groups have formed an international consortium called TrialNet to pursue this huge goal. I'm pleased to be joined by two NIH diabetes researchers, Dr. Ellen Leschek and Dr. Lisa Spain, and Cynthia Rice, senior vice president for advocacy and policy to the Juvenile Diabetes Research Foundation.

 

I want to start by asking you all, type I diabetes, it's really a different disease from type 2 diabetes, isn't it? How's it different for patients?

 

ELLEN LESCHEK: Type I diabetes is historically known as juvenile diabetes. But in truth, it can occur at a variety of ages, including adults. The main difference between type 1 and type 2 diabetes is that type 1 diabetes is caused by an immune reaction that slowly destroys the pancreas, which is the organ that makes insulin. Whereas in type 2 diabetes, you have plenty of insulin coming from the pancreas.

 

But your body is not responding to that insulin.

 

STEVE USDIN: So type I diabetes is an autoimmune disease maybe more similar to multiple sclerosis or rheumatoid arthritis than type 2 diabetes.

 

ELLEN LESCHEK: Exactly.

 

STEVE USDIN: What are the consequences, the burden for people, for individuals who have type 1 diabetes? What's it like to live with it, and what's the burden on society?

 

CYNTHIA RICE: I can say that type 1 diabetes, you immediately need insulin. And you need to with every meal, day and night, 24 hours a day, seven days a week, 365 days a year, manage this disease, because if you take too much insulin with a meal, you can have a low blood sugar and need to go to have an emergency, need to go to the hospital, or be revived. If you don't take enough insulin, you have the consequences of long-term complications -- heart disease, strokes, kidney failure.

 

So it's a constant balance. And that's really the challenge with type 1 diabetes is, people often get it a very young age, sometimes as youth, also as adults. And then they have it for decades, and they have to manage this seesaw each and every day for this very dangerous disease.

 

It's very complicated to manage on a daily basis. Parents set their alarms at 2:00 in the morning to check their kids' blood sugar to make sure it hasn't gone too low, so they don't basically have a seizure in the middle of the night. It requires the whole family and community to manage this disease.

 

STEVE USDIN: So the ultimate goal, of course, would be to be able to prevent it or to reverse it or at least at a minimum, to delay it. Right now, what can we do? Can we confidently say that we can prevent it or delay it now?

 

LISA SPAIN: Unfortunately, no, Steve. But I think there's a great opportunity in type 1 diabetes. One of the interesting aspects of the disease relative to other autoimmune diseases is that the process of autoimmunity that builds slowly over time occurs without you noticing it. So people have an autoimmune process that's ongoing long before they actually develop the symptoms of the disease.

 

But nevertheless, through clinical trials and science experiments, we've been able to show that we can identify children who are at risk for the disease, through a combination of tests of their genetics and tests of autoantibodies in their serum. And so for some classes of children, we can actually detect that they have an 80% risk of developing type 1 diabetes in the next five years.

 

And this provides a scientific opportunity to do research to understand whether we can prevent the disease.

 

STEVE USDIN: And that gets us to TrialNet, which is a big effort that NIH has launched internationally to try to identify people who are at risk of getting type 1 diabetes and to see if you could have interventions that will prevent it. Can you walk us through it first the screening aspect of it?

 

Who are you screening? How are you doing it? And how is it going so far?

 

ELLEN LESCHEK: So TrialNet is screening first and second degree relatives of people with Type 1 diabetes to determine if they are at risk. And TrialNet was launched back in 2001, following a short study about whether or not a treatment called oral insulin could prevent or delay diabetes.

 

STEVE USDIN: But on the screening, it's a simple blood test that people do?

 

ELLEN LESCHEK: That's right. So it is a simple blood test. It's a single blood draw that can be done either at one of our clinical centers or affiliate centers. Or it could be done remotely. We can send out a kit, and people can take it to a local laboratory and have the blood drawn and sent into the lab to be tested. And between 2% and 5% of the relatives that we test will come back at risk for the disease.

 

And then we bring them back, and we help to determine what their level of risk is. And then depending on what their level of risk is, we hopefully have a prevention study to offer them.

 

STEVE USDIN: So it's a little bit like a needle in a haystack there if you're talking about 2% of people whose relatives have type 1 diabetes come back, and it turns out that they're at risk. How many people have you screened so far?

 

LISA SPAIN: So we've screened already over 100,000 children in type 1 diabetes TrialNet. And we screen at a rate of around 16,000 per year. And we'd like to do more. We have a lot of families out there that have the disease in their families. And the more we can screen, the more research we can offer participants, and the more we can learn about the disease and move towards preventing it.

 

STEVE USDIN: Well, we're going to continue our discussion of type 1 diabetes in a moment. Later, we'll have this week's Affordable Care Update. First, here's a snapshot of how treatment advances are helping people live with the disease.

 

[MUSIC PLAYING]

 

NARRATOR: You're watching BioCentury This Week.

 

SEGMENT 2

 

STEVE USDIN: We're talking about type I diabetes with Dr. Ellen Leschek, Dr. Lisa Spain, and Cynthia Rice. We were just talking there about screening for TrialNet, and you mentioned screening children. You're also screening adults, right?

 

LISA SPAIN: That's true. We know that type I diabetes incidence does occur in young adults and all the way up to age 40 can be involved in TrialNet.

 

STEVE USDIN: Do we know anything about the causes of it? It must not be that heavily genetic if you're saying it's only 2% of relatives that are likely to have it.

 

There are both genetic causes and environmental causes of type I diabetes. And one of the great things that NIH is doing is, they're not only funding prevention trials to make sure that we can test therapies to try to prevent type I diabetes. But they're also funding a long-term study that is testing essentially what are the environmental triggers. When someone is genetically at risk, what might cause the auto immune system to start going haywire?

 

And so that's one of the important long-term studies that NIH is funding now, because there are clearly both genetic risks and environmental risks. When you have two identical twins, one can have type I diabetes and the other one doesn't necessarily have it. It's more like a 50/50 chance of the second twin having it.

 

STEVE USDIN: I want to get back to TrialNet then. You screen people, you find that individuals who have the antibodies that suggest that they're likely to progress to get type I diabetes. Then what happens?

 

ELLEN LESCHEK: So once they're identified as being at risk, we follow them. We check them periodically to see whether they're progressing to disease. And hopefully we have a prevention study that we can offer them participation in. And we have several different prevention studies ongoing right now.

 

There are two that are for people who are at moderate risk for disease. Those are the oral insulin study, which involves taking a capsule of insulin by mouth in order to hopefully induce some sort of tolerance and prevent diabetes. The other one is a trial using a marketed drug called abatacept, which is also known as Orencia. And that study is also for moderate risk, as I mentioned.

 

And then we have a study for high risk individuals. These are individuals who are at very high risk for developing type 1. They are in the range of about 80% at risk of developing it over the next five years. And that study we're using an agent called Teplizumab that hopefully will do something to change the immune response so that we can delay or prevent the onset of diabetes.

 

And the people in that particular study are already showing some signs that they're not managing their blood sugar very well. They're already starting to lose control of their blood sugar. But they're not fully diabetic, but they're certainly on their way.

 

STEVE USDIN: You mentioned oral insulin. That's an interesting thing, because most people think of insulin as something that's infused, that's injected. How does oral insulin work? And what's the data that suggests it might lead you to be able to prevent type I diabetes onset?

 

LISA SPAIN: So the major fund of data that supports that trial is actually the precursor to TrialNet, which is called the Diabetes Prevention Trial Type 1 or the DPT1. And in that trial, there was actually two arms. And one was in injected insulin arm in people at risk for type 1. And then there was also this ingested, or oral insulin arm of the trial.

 

And in that trial, although overall, the results were negative in that neither treatment seemed to prevent type I diabetes, in a subset of individuals with the highest levels of autoantibodies to insulin, they showed a modest delay. And that is what this new trial is intending, to really get in there and to determine whether that can be followed up. And so the rational here is that our body has an immune system, which is really designed to protect us against pathogens and infectious diseases.

 

But when you have the genetic predisposition for auto-immunity, there's a failure of the immune system to be properly regulated. And so there's a response against--

 

STEVE USDIN: It's almost like a vaccination. You're priming the immune system to recognize the insulin by continuously exposing yourself to it.

 

LISA SPAIN: By exposing it at musocal surfaces, it will be.

 

STEVE USDIN: The success of TrialNet depends on screening tens of thousands of people to identify those with risk factors for type 1 diabetes. Here's how you can learn more about participating in TrialNet.

 

[MUSIC PLAYING]

 

SEGMENT 3

NARRATOR: Now, back to BioCentury This Week.

 

STEVE USDIN: We're talking about type 1 diabetes with Cynthia Rice, a policy expert at the Juvenile Diabetes Research Foundation, and two NIH researchers, Lisa Spain, and Ellen Leschek. I wanted to ask you, if TrialNet works, isn't the implication of it going to be that you're going to need a massive screening campaign, that you're going to have to screen everybody?

 

ELLEN LESCHEK: Well, if TrialNet is able to identify something that successfully delays or prevents diabetes, then hopefully what would happen is that we would bring that screening to the general population once we find something. We're still in the early stages of trying to identify things that are safe and effective. And once we do, hopefully something maybe on the order of a vaccine would be available.

 

And at that point, maybe we would be vaccinating people.

 

STEVE USDIN: And if you don't have a vaccine and you have to screen people, another question I wondered is, some people develop, about half under age 18 and about half over 18. So might you have to actually screen people more than once in their life?

 

ELLEN LESCHEK: Yes, and actually, TrialNet does screen people more than once. If you get screened by TrialNet and you come back negative, depending on your age and such, we may ask you or offer for you to come back in another year and be screened again, and then maybe again in another year, because we do know that the autoimmunity can develop over time.

 

STEVE USDIN: When are you going to have results that might be actionable from TrialNet?

 

LISA SPAIN: I think it's going to be at least another five years before we have any of the results in our longer term prevention trials. As we mentioned, the screening rates, we need to do a lot of screening and identifying people and enrolling them. And the rate of progression of the disease is actually very slow.

 

So we have to wait a long time to get results. But we have very patient patient population who are in it for the long term. And we have dedicated staff that make sure that these children and their families keep coming back, and adults.

 

So it's a long term effort.

 

STEVE USDIN: I want to switch to something that's shorter term that the JDRF is working on. And I should say, you've changed your name from the Juvenile Diabetes Research Foundation to JDRF. The Artificial Pancreas Project -- what is it, what's the status?

 

CYNTHIA RICE: So the Artificial Pancreas Project is a really exciting initiative. Our goal in that initiative is to develop a system that would automatically give the right amount of insulin at the right time. And so that would enable someone with type 1 diabetes to have much better control, which, in the long run, would prevent kidney failure and heart attacks and long-term complications of diabetes. But also, it would prevent those short-term emergencies, when someone has a low blood sugar and they have to immediately go to the emergency room.

 

And the way it would work is, it would combine a series of external devices, which already exist -- there is continuous glucose monitors, and there are insulin pumps. And JDRF and NIH have both funded some of the world's most accomplished mathematicians to develop complicated algorithms to basically take the continuous glucose data and translate that into the right amount of data at the right time. And right now, we're still in the feasibility stage.

 

But we have academic studies where people with type 1 diabetes are walking down the streets of Charlottesville, Virginia, along with their UVA researchers and going out to dinner at restaurants and actually having the device respond to the meal that they ate and give them insulin. So it's really exciting.

 

And there are several companies that have a development pathway underway to create those devices.

 

STEVE USDIN: So when I spoke with you and I think some other people from JDRF a year or two ago, there was some concern that the regulatory pathway was a stumbling block. And things weren't moving forward. There was a little frustration there. What's the situation with that now?

 

CYNTHIA RICE: Well the really good news is, as a result of all the work that we did with FDA, there is now official guidance that FDA has put out, which does lay out a clear and reasonable pathway for the development of the artificial pancreas, because like prevention, the artificial pancreas, in order for it to get to people with type 1 diabetes, we need the entire ecosystem to do its part.

 

We need funding at NIH, we need organizations like JDRF giving funding, we need a regulatory pathway, we need companies that are going to translate these into products and ultimately be the ones to bring it to people. And we need the healthcare system to pay for it. So the FDA has approved a lot of these in patient studies, and they've now laid out a clear and reusable pathway. So we're really excited about that.

 

STEVE USDIN: So very quickly, when do you think we'll see approval? When do you think we'll see a device that patients can get?

 

CYNTHIA RICE: Well, the artificial pancreas will be in stages. And the very first step to an artificial pancreas was just to approved in the last month, which is essentially a threshold suspend system that would turn off insulin when someone goes low. So that very first product is on the market.

 

In terms of when the next generation and the versions that will automatically give insulin will be available, I think we just need to get a little further down the development pathway before we can say.

 

STEVE USDIN: Coming up, this week's Affordable Care Update.

 

NARRATOR: Healthcare is changing, and we are changing too. Each week, watch BioCentury's Affordable Care Update, a special part of every show, dedicated to keeping you informed about this unprecedented transition. And watch all of the weekly updates in one place at any time only at biocenturytv.com.

 

SEGMENT 4

 

STEVE USDIN: To discuss what the Affordable Care Act means for patients with chronic diseases like Type I diabetes, we're joined by David Nexon of AdvaMed, the Advanced Medical Technology Association. David, it seems like the website, healthcare.gov, is working reasonably well now. And I think that the attention's probably shifting to some of the underlying aspects of the Affordable Care Act. What do they mean for people with chronic diseases like diabetes?

 

DAVID NEXON: Well, Steve, I think that there are some really positive things in the Affordable Care Act for people with chronic diseases, including diabetes. There are also some yellow flags that we need to pay attention to and perhaps make some alterations of the laws that moves forward. On the good side, of course, the interest of people with chronic diseases is having access to the medical care that's most appropriate for their needs, including medical technology of the kind that the companies in our association manufacture.

 

First of all, the Affordable Care Act expands coverage to millions of people. So for the first time, they have access to care that they would not otherwise have, because they now have insurance. In addition, the Affordable Care Act prohibits insurance companies from putting either annual or lifetime limits on the amount of care that they'll cover. And again, for people who with chronic diseases, who often have very high cost care, that's an important benefit not to have their insurance run out when they need it the most.

 

STEVE USDIN: And the other thing, then, that's really important is that it bars insurance companies from discriminating against people who have preexisting conditions.

 

DAVID NEXON: Absolutely. That's right.

 

STEVE USDIN: So the yellow flags. What are the yellow flags for you?

 

DAVID NEXON: Well, I think there are two. As part of the bill, they set up new systems for Medicare to pay hospitals and doctors. And those systems are things like accountable care organizations -- are designed to provide incentives for lower cost and higher quality. And that's a good thing to do. But the problem is that the incentives for lowering costs are quite strong, whereas the measures of quality to ensure that we're not stinting on care relatively weak. So the danger is, particularly for people that need high cost care, like those with chronic diseases, you could have a situation where to save money or to make money, providers are not giving them really the best care that they need but are taking into account cost in a way that's not appropriate.

 

STEVE USDIN: So who's going to be watching that? And if there needs to be some kind of an adjustment, do you think we're in a political climate now or going to be in the next year or two where there actually could be adjustments to the law?

 

DAVID NEXON: Well, I'm hopeful that that's the case. Certainly, CMS is overseeing the program. And they are doing some things to try and assure that stinting on care doesn't take place. We have some concerns that those things might not be adequate. They can be addressed, I think, administratively by CMS in many respects. To the extent that legislation is needed, as you point out, it's difficult in this climate. But I'm hopeful that within a year or two, things will settle down to a more normal kind of legislative environment where people will be making corrections in the law rather than fighting over whether it exists.

 

STEVE USDIN: And what's the second thing? You said there were two yellow flags.

 

DAVID NEXON: Yeah, the second one, which is more of a long-term thing, which is people with chronic illnesses, in fact, all patients don't just want to get the best care that's available today. They want the treatments and cures of tomorrow to be developed. We've had a tremendous record in this country. We're between an agreement between universities, medical researchers, the NIH, and device companies and drug companies to develop new treatments and cures. And we've seen tremendous progress.

 

Just in the last 10 years, we've increased life expectancy by two years, we've cut into the death rate from heart attack and stroke by more than a third, the death rate from breast cancer by almost 20%, disability amongst the elderly by 25%. So this is a century of biology.

 

So we have a wonderful opportunity to move forward. The problem, again, goes back to these incentives to control cost. And if you don't make some specific adjustment for new treatments, it may be that they won't be able to get into the marketplace or not get into the marketplace as fast. And that drives up the pipeline people's willingness to invest in their developments.

 

STEVE USDIN: So how are the concerns that you've mentioned about cost containment relate to something like the artificial pancreas, other kind of high technology devices?

 

DAVID NEXON: Well, there's an awful lot of money that goes into developing those devices. And before people put that money in, they have to think that there's going to be a return on the other end. If they feel it, because of the financial incentives, providers, doctors, hospitals, are going to be unwilling to adopt those new technologies. They won't make the investment, and they won't get developed. That's sort of the long and the short of it.

 

STEVE USDIN: And that's the high tech end of it. What about the low tech end of it? There are aspects of the Affordable Care Act that are driving down the costs of durable medical equipment, things like test strips for diabetics.

 

DAVID NEXON: Again, that's a change to Medicare that was accelerated under the Affordable Care Act. And what we've seen happen is that as a result of the competitive bidding program that they put in for those test strips, prices have been driven down tremendously low, which is not a bad thing, except they're so low now, that none of the name brand manufacturers feel they can participate in that market. And that means the patients aren't going to get the test strips that they're used to, and their doctors may think work best with the glucose monitors that they've been using.

 

STEVE USDIN: Isn't that kind of part of the price of any kind of reform. If one of the purposes of healthcare reform is to lower costs there's going to be changes. Somebody's going to have to endure some kind of a change from what they're used to. You can't keep doing everything the way it has been doing and lower costs.

 

DAVID NEXON: That's absolutely true. But the issue is how much do you need to lower costs and what kind of protections do you need to put in to make sure that in the pursuit of lower cost, we're not harming patients because nobody wants that to happen.

 

STEVE USDIN: And one of the other aspects of the Affordable Care Act -- something that people with chronic conditions really need is better coordination of care. Do you think that the Affordable Care Act is really going to lead to this better enhanced coordination?

 

DAVID NEXON: Yes, I do. I think that the provisions in the Medicare program to reform the payment system, particularly the accountable care organizations, which I know you've discussed on the show before, really provide an incentive and a financial mechanism for providers to concentrate on doing the things that keep people healthy, living well with their disease, and staying out of the hospital, because that also reduces cost. And that's potentially a really important step forward for people with chronic illnesses.

 

STEVE USDIN: I want to ask you really quickly about one other aspect of AdvaMed's legislative agenda, which is the device tax. Where does that stand?

 

DAVID NEXON: Well, we're cautiously optimistic. We've had overwhelming bipartisan support in both the House and the Senate. But there's still significant opposition. But we're hoping we're going to be able to get it passed, because it's a tremendous strain on our ability, our industry's ability, to compete and to create the new treatments and cures which are so important to patients.

 

STEVE USDIN: Well, thanks. That's this week's show. I'd like to thank my guests, Ellen Leschek, Lisa Spain, Cynthia Rice and David Nexon. Have a thought about today's show? Remember you can tweet about using the hashtag #biocenturytv. I'm Steve Usdin. I'll see you next week.

 

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