Ep 55: George Vradenburg - Advancing the Science of Alzheimer’s Prevention (part 2)

Breakthrough advances in research coupled with health-conscious strategies around brain health continue to bring us closer to the prevention of Alzheimer’s and related dementias In part 2 of a conversation with George Vradenburg, Chairman and Co-Founder of UsAgainstAlzheimers, discusses the shift in the Alzheimer’s treatment paradigm as well as prevention that comes along with people taking ownership of their brain health. Medicine, along with a healthy lifestyle, can reduce the risk of Alzheimer’s and other diseases. Listen as we discuss what the future holds when it comes to beating this disease globally. 

Co-produced by Susan Quirk and Amber Roniger

Transcript

Quote (00:01):

I've lost three generations already to this disease, a grandparent, a parent, and now a brother-In-Law, we're fighting against a disease that's affected both of us. You've been affected differently with a husband and a mother that you've cared for for so long. So we're on this path together and we are committed to make sure it doesn't happen to us or to our kids, or to our grandkids. And I think we now have a path to that solution if we can execute on it.

Opening (00:32):

Welcome to BrainStorm by UsAgainstAlzheimer's, a patient center, nonprofit organization. Your host, Meryl Comer, is a co-founder, 24 year caregiver and Emmy Award-winning journalist and the author of the New York Times bestseller, “Slow Dancing With a Stranger.”

Meryl Comer (00:49):

This is BrainStorm and I Meryl Comer in part two of our conversation with George Vradenburg, Chairman and Co-Founder of UsAgainstAlzheimer's with its agenda, both domestic and global. I asked him about the 2023 Lausanne 10 conference in Switzerland and the shift in the Alzheimer's treatment paradigm to include disease prevention through brain health.

George Vradenburg (01:13):

Well, as you know, there are two fundamental strategies of how to get at the prevention of this disease. One is a medicine that actually interferes with the biological processes of the brain that will prevent Alzheimer's symptoms. The other is whether or not through the treatment of risk factors for future Alzheimer's symptomatic disease, you can interfere with those risk factors in a way that will prevent large segments of people at risk from ever getting the symptoms of the disease. So there was not much discussion in Saudi Arabia about the prevention strategies except in this respect. We all now know that heart disease, hypertension, diabetes are risk factors for Alzheimer's. And so if you can find drugs that successfully defeat hypertension, all the other metabolic conditions, you will have taken a medicine intervention to reduce the risk factors, accompany that with modifiable behaviors, diet, exercise, sleep, don't smoke, don't drink too much.

George Vradenburg (02:22):

You may be able to add the power of not only reducing metabolic disease and reducing the risk of Alzheimer's by doing that, but also by doing it through these modifiable risk factors. There's a challenge here because no one has really demonstrated other than sort of in a public health sort of data way that that is all true. What's interesting about this latter part is that with these brand new drugs that have come out from Novo Nordisk and from Eli Lilly that actually affect your diabetes and affect your heart disease in positive ways and will they actually reduce the risk of Alzheimer's, those drugs are now being tested in new clinical trials to determine whether they can reduce the risk of Alzheimer's. Add to that, the modifiable behaviors that when added to reducing metabolic disease prevalence, you can actually have a multi-pronged strategy, a combination of modifiable behaviors plus drugs that deal with the risky comorbidities that increase the risk of Alzheimer's.

George Vradenburg (03:29):

You can have a double whammy on that. And so this is an exciting time in a sense, but we are just starting now. Of course, the major challenge here is less on the medicine side. We now have these GLP ones that in fact can affect these comorbidities. It's how to get people to change their behaviors. And so there's some interesting work that has come out of Mass General that I just read from the McCants Institute. Henry McCants, as you and I know, started to cure Alzheimer's fund many years ago, but he also started something called the McCants Center at Mass General. And what they've developed is a brain care score where you actually score all of the associated risk factors. You put a number to it and you get a brain health number. Now I remember that Kay Jong did this years ago at Cleveland Clinic.

George Vradenburg (04:17):

It never sort of scaled, but McCann Center has now put this on and they now had the first study using 400,000 people out of the UK Biobank to test whether or not you can associate a difference in the behavioral risk factors of Alzheimer's and get a better result. The first study out shows very positively that you can do that so that if you have a brain health bearing care score of 21, you'll be perfectly healthy. If you have a brain care score of 15, you're less likely, but a brain care score of 10 and you're going to be at risk for these diseases. And then they rank nutrition, exercise, sleep, liquor, cigarette smoking, all the behavioral risk factors and give you a number. Maybe if we, you know, start using numbers, we'll say, Meryl, what's your number? And then I'll tell you what my number is, then we'll start competing to behave better, to reduce our risk of dementia.

Meryl Comer (05:13):

When you talk about numbers, my philosophy is you've got to stay healthy until the science catches up

George Vradenburg (05:18):

<Laugh>. Well, that's true, but how do you get people to do that? Obesity rates are going up, hypertension rates are going up. Now heart attacks are going down because we're doing better at emergency care but not preventing the initial heart attack. And so we use statins now not to prevent the initial heart attack, but basically after you've had a heart attack to reduce the risk of a second heart attack. We have now these GLP ones that will reduce your diabetes risk, but obesity is going up, diabetes is going up, and so you and I can stay healthy, Meryl, but most of the American people and indeed people around the world are having increasing prevalence of hypertension and diabetes. We have to find a way to enable something more than just saying, be smart about your health. People just aren't. And the fast food industry of the United States is not our friend.

Meryl Comer (06:06):

George, let's come back to some realities here at home. In 2011, the annual federal investment in Alzheimer's research was 448 million. You remember that?

George Vradenburg (06:19):

I sure do.

Meryl Comer (06:20):

Well today the budget is more than 3.7 billion. Are you concerned that the funding support in this Congress is swinging away from its increases for NIA funded research on Alzheimer's?

George Vradenburg (06:34):

Well, you and I will recall Meryl that when I was at 448 million a year, we were told that it would be impossible to persuade Congress to over allocate to one disease over another, that if you did that from the Alzheimer's community, you'd simply have the cancer community dropping a bomb on us and we would never make it anywhere. And you and I changed that paradigm. We made the case that in fact, if the costs of care to Medicare and Medicaid over the next 15 to 20 years we're predictably going to be greater than the Defense Department budget, that it is absolutely insane for the United States government to not invest more than what they were investing at the time against that disease. And we had great champions in both sides of the aisle, both Republicans and Democrats. One of the strongest champions was a conservative Republican from Missouri, Roy Blunt.

George Vradenburg (07:24):

And he every year championed significant increases in part because we in 2012 committed the nation to be able to prevent Alzheimer's by 2025. And every year NIH is required to give directly to Congress a budget proposal that says we need this much additional money in the following year's budget if we are to hit that 2025 goal. So setting the goal as we did and advocated for back in 2011 and 2012, Merrill has produced a mechanism that has caused these increases every year. Now you ask whether those will continue. I think the answer is probably not, probably not, not because people are turned off on Alzheimer's, but because the government's deficit is so large now and the interest costs on that deficit are so great now that there will be a very strong push to try and control government spending as well, maybe from the Democrats raise taxes and the Republicans to reduce spending. And so I think there's going to be enormous pressure in the short term here on government budgets generally not no allergy to raising Alzheimer's, spending specifically, but to raising NIH spending. We'll continue to fight, but I think that you know, substantial risk that we will not be able to get the same level of increases for Alzheimer's research every year as we have in the last eight or nine years.

Meryl Comer (08:47):

George, let's look at the FDA approval of two early disease modifying therapies. What challenges arose that were unpredicted in the aftermath of those approvals?

George Vradenburg (09:00):

Well, the first drug that was approved by the FDA was a drug called Aducanumab from Biogen. And it had been through two clinical trials, one of which was positive and one of which was perceived as negative. And as a consequence, the FDA was confronted with what many would say would be lack of clarity in the scientific evidence that that drug actually was interfering with the course of the disease and could reasonably be thought to predict clinical benefit. The FDA looked at that, they looked at it closely, looked at it over a period of time and concluded that the positive clinical trial was more persuasive, that the reason the other one failed was that people weren't on the drug as long and that therefore they could confidently say to approve the drug on the pathway that Medicare provided long ago for HIV aids and now uses frequently with cancer that if you've interfered with the biological process of a disease, you can reasonably predict that you're going to get a clinical benefit even though you haven't proved that people yet have lived longer.

George Vradenburg (10:01):

You can reasonably predict that a reduction in the size of a tumor is going to produce a clinical benefit of some dimension even though you haven't had a cure for HIV aids. So they established this pathway to approval for a large unmet need that if you could prove that you've demonstrated an interference with the biological process of a disease, you could reasonably predict that it had clinical benefit and you could approve the drug and then require the drug sponsor to perform a confirmatory trial. Well, that was a highly controversial decision and Medicare decided that because there was not a demonstration of clinical benefit, it would not cover that drug. And indeed it made a decision. It would not cover any drug that used the same mechanism of reducing beta amyloid in the brain, even though there's only one drug in front of them. They had never in the history of Medicare not covered a drug that had been approved by the FDA. So we ran into what was, as you put it, an unexpected wall to giving this drug to people who couldn't afford the full $26,500 price for this drug. And so it was a bit of a political fight where we had almost 40% of the members of Congress either write or call Medicare to say it's unconscionable that there is a drug that has been approved by the FDA that has demonstrated an interference with the biological process and they've concluded that it's reasonably likely to produce clinical benefit and only wealthy people can get access to it.

Meryl Comer (11:27):

George, not only was this a case where political interference in patient advocacy were intensely involved for over a year in changing the politics of this coverage decision by Medicare, but didn't it also set the stage for the next drug in the pipeline?

George Vradenburg (11:43):

Since that time, the second drug came out, which happened to have a clinical trial process that showed a clinical benefit in large phase three trial. That was helpful because that demonstrated to Medicare that in fact this was not a wild scientific theory, but one in which you could demonstrate clinical benefit. And they changed their mind, they changed their posture, and as a result of that, they've actually changed their posture on whether to reimburse for these expensive PET scans that are required to detect whether or not you've got amyloid in your brain. And they changed their decision on that and they are now covering those scans. But we know that Medicare is now determined that it is not going to cover drugs that haven't proved clinical benefit, and that means very big, long and expensive trials that they're not going to cover drugs approved on this more accelerated pathway designed for high unmet needs where you've shown inability to interfere with the disease. So that comes back to your earlier questions about vaccines. Will regulators actually approve a vaccine based upon its demonstrated scientific ability to interfere with something that relates to the disease? Will Medicare cover those vaccines right now? The posture will be, no, not unless you've had a trial, probably tens of thousands of people that demonstrates that in fact it is safe and effective, notwithstanding the FDA's judgment that it is, we have to watch and see with confirmatory trials whether it actually is successful.

Meryl Comer (13:06):

George, can you point to progress on these intractable issues like equity and broad-based prevention?

George Vradenburg (13:15):

I think the answer is yes, we're making progress, but it's way too slow. So there are two aspects of equity. Is it fair and right that we conduct clinical trials on a medicine that will be introduced into the population when you have not included a representative sample of the entire population in those clinical trials? That's in part a fairness issue. It's in part A, will this drug work for me if I'm black, if I'm Latino, if I'm Asian, if I'm a woman, not a man, will this drug work for me? So that goes to sort of the trust that the American people will or will not have in whether or not the drugs that have been approved by the FDA have passed that hurdle of did you try it in people like me, the clinical trials on these drugs that we've been talking about, which started 10 years ago, did not do a good job in including minorities in their clinical trial population.

George Vradenburg (14:05):

Many of the clinical trials in the past have been done in academic institutions that are pretty inaccessible to minority populations, not used by them, not in their neighborhood. The other aspect of minority equity is whether or not the drugs are going to be made available to the populations that are low income, rural or minority populations. And since the first round of drugs are very high cost require infusion and require PET scans in order to determine whether you've got the underlying disease, again, we don't have a system yet that has been able to assure that there is equitable access to the medicines that do come through the clinical trial system. In fact, we are working now with the federally qualified health centers, 1400 of them that basically work with minority populations, largely Medicaid and low income populations and rural populations to try and get them schooled up on what it's going to take to actually identify the patients that are appropriate for these drugs. And then as you've indicated earlier in our conversation, the effort to try and get these drugs or some drugs or prevention strategies into low and middle income countries around the world, we're working so very hard on. The whole effort on the vaccine front is part of that effort to satisfy our moral responsibility to work on solutions to preventing Alzheimer's which are available to all people and not just the wealthy and high resource countries,

Meryl Comer (15:30):

George to the man who rewired. Instead, were retiring to rally and transform political advocacy in the fight against Alzheimer's disease to a man who believes in setting ambitious goals. What's your forecast for what we might achieve by the year 2030?

George Vradenburg (15:47):

I have a target of trying to get a vaccine on market by 2030. It will be a secondary prevention vaccine that is a vaccine that's given to people who are high risk for the disease and take the vaccine in order to both lower the proteins that are affecting the course of their disease and preventing its continued accumulation. So be able to detect the emergence of these toxic proteins at the very opening gun and basically like a shingles vaccine, you take it at age 50 and age 55 and 60 so that you basically adhere to a vaccine regime, which is a primary prevention regime, not a secondary prevention regime. Secondary prevention 2030, primary prevention 2040 with modifiable behaviors. I think that's a greater challenge. I think trying to change human behaviors challenging. One of the things that us against Alzheimer's is doing is actually working with business as employers to say, how is it that you can begin to measure the brain health of your employee base, not just in suppressing disease, although obviously that's helpful, but also in motivation because we know that people with purpose and with a meaning in life live longer.

George Vradenburg (16:58):

That is a major new effort on our part to try and attack this prevention effort. And it is styled around brain health, not around just reducing the risk factors for brain disease, but now brain health. I think that there is a great future in cognitive training tools and I think there's a great future for digital interventions. We hear rumors that some companies are looking at digital tools that will foster the imagination. Digital tools that will foster creativity, not just training, processing speeds in your brain, but actually affecting those areas and connections in your brain that go to imagination and purpose and meaning in life. Those things could be a potential real game changer in terms of actually changing our attitude towards brain health and our brain health overall.

Meryl Comer (17:48):

You projected out 2030 and then went to 2040 and it brings us back to the original goal when you founded us against Alzheimer's was we wanted to solve this in time for our children and our grandchildren.

George Vradenburg (18:03):

Well, Meryl, you and I did that goal setting. You were there as a co-founder of this whole effort. So you and I have been in the trenches here for a long time, but we're beginning to make progress and we've clearly gotten much more elaborate on how we're going to do this. And in a sense, the strategy has become clearer. The execution is still wanting, we still have to execute on those strategies. But you and I, through us against Alzheimer's and our sister companies have basically got a strategy in mind of how to do this. And we have got support. We got support around this because basically the patients which we represent, people living with this disease, the families living with this disease have an enormous moral power to convene people around getting a strategy and executing a strategy that will solve this disease. My kids, I hate to say this because it'll disclose my age, but my kids are about 50 years old.

George Vradenburg (18:58):

If we're there in 10 years, I think my kids will be okay. If it's 20 years, it's closer. But if in 10 or 20 years we have the means of preventing this disease, I think I'll save my kids. But as you know, I've lost three generations already to this disease, a grandparent, a parent, and now a brother-in-Law, we're fighting against a disease that's affected both of us. You've been affected differently with a husband and a mother that you've cared for for so long. So we're on this path together and we are basically committed to make sure it doesn't happen to us or to our kids or to our grandkids. I think we now have a path to that solution if we can execute on it.

Meryl Comer (19:41):

Our guest today, George Vradenburg, visionary chairman and co-founder of us against Alzheimer's, committed to putting patients, families and equity first, along with launching a network of spinoff initiatives to galvanize support and offer solutions globally to beat this disease. That's it for this edition. I'm Meryl Comer. Thank you for brainstorming with us. Our team is on a mission to help you stay up with the latest scientific breakthroughs from new therapies to technologies on early diagnosis and personal brain health advice from well-known experts using an equity lens that promotes brain health for all. Now we'd like to hear what's on your mind, what are the topics and guests you'd like to hear featured on brainstorm? Send your comments to BrainStorm@usagainstalzheimers.org.

Closing (20:36):

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