Ep03: Pioneering Progress: Advancements in Alzheimer’s Immunotherapies, Vaccines, and Screening

[00:00:04] Dan Kendall: Welcome to the Brain Health News Podcast, part of Health UNMUTED. 

This podcast was created by Mission Based Media in association with the Davos Alzheimer's Collaborative. 

This was recorded live in January, 2024 at the World Economic Forum Annual Meeting in Davos, Switzerland. 

This episode is hosted by Richard Lui, an author, filmmaker, and anchor at NBC and MSNBC. He and his two guests discuss the latest developments in Alzheimer's research. They delve into the breakthroughs in immunotherapy, the potential for early intervention and the impact of new diagnostic methods, 

and importantly, they also explore the role of partnerships and collaborations in advancing Alzheimer's research and the global effort that's needed to achieve this goal. 

Enjoy this conversation hosted by Richard Lui. 

[00:00:49] Richard Lui: Great to see all of you at the Davos Brain Health Impact Conversations with the Davos Alzheimer's Collaborative, DAC. And my name is Richard Lui. It's great to be here to have a very good discussion with all of you, we hope. I'm at NBC and MSNBC. I'm also person that used to be a caregiver, my father had Alzheimer's.

This is why I'm so glad to be here for this conversation. We're in the studio with expert and advocate Dr. Andrea Pfeifer. She is the CEO of AC Immune SA, a Swiss company developing new medicines for Alzheimer's disease. She is globally recognized as a leader and strategist in the field and chair of the Global BHP BrainTrust.

Good to see you. Shall I call you doctor? Is that okay?

[00:01:29] Andrea Pfeifer: Andrea is fine. 

[00:01:30] Richard Lui: Andrea, okay, very good. We're also joined by my friend, fellow Alzheimer's advocate and the founding chairman of DAC, the Davos Alzheimer's Collaborative. Always great to see you, George Vradenburg. Welcome to you both. And we'll kick it off with you, Andrea.

What are some of, if we're just hopping into these conversations, some of the developments that you've been watching lately in the Alzheimer's space? 

[00:01:54] Andrea Pfeifer: Obviously, we had a wonderful 2023 year with lecanemab being approved, donanemab being very close to approval. It was a major breakthrough because the first time in the last 20 years of history, that was a real breakthrough, meaning we can slow down the disease.

[00:02:14] Richard Lui: And that meant a lot, didn't it? Because how long had it been since we had a bit of a glimmer, if I may undersell it for a moment? 

[00:02:23] Andrea Pfeifer: Glimmer? I'm not sure what you would call a glimmer, but to have a real scientifically proven benefit of 30+ percent is absolutely a unique experience. And obviously, there was a lot of learning involved.

And maybe just to summarize that, the long disputed, a better hypothesis was validated. We could actually show that immunotherapy can target these pathological species in the brain. And thirdly, we learned that, if you treat early, you can have even more effects. So there was a lot of learning involved, which of course opens up a horizon for new medication. And that's my interest. 

[00:03:04] Richard Lui: So you and George don't get along at all, I imagine. 

[00:03:07] George Vradenburg: Oh, yes, we spend a fair amount of time together. I am an enormous admirer of Andrea Pfeifer. 

[00:03:13] Richard Lui: So, tell me about, she was just remarking about this 2023, care about. 

[00:03:20] George Vradenburg: I would echo what she said about the hope. After all, this disease was identified in 1906, 117 years later, it's the first time we have a molecule that can interrupt the course of the disease to slow it down. Huge difference. But what Andrea has just highlighted is the fact that since we now know this disease accumulates these toxic proteins 25 to 30 years before symptoms, the idea that you can actually give a drug or a medicine or an active immunotherapy, otherwise known as a vaccine, to people well before they ever get symptoms and prevent the buildup of these toxic proteins is exciting possibility.

To opens the imagination to something, in fact, we had never thought possible. 

[00:04:08] Richard Lui: So what does this mean now, or in 2024? What does this mean for the next five years? 

[00:04:14] Andrea Pfeifer: I think, we are all looking at what is next. And for me, next is moving to intervention, even at an earlier stage. Even data from the antibodies actually showed that if you use the same molecules in earlier stage, you have double the effect, so we are going earlier. But hopefully we will be able to actually prevent the disease. And for that, we need to diagnose when the people don't have yet the symptoms and there are means available. And we need to look for medications which allow you to treat in a way where we have excellent safety, excellent efficacy, which is cost effective and logistically doable. So that's what we are looking at, and if you ask me, first active immunotherapy by 2029. 

[00:05:04] Richard Lui: Okay, you heard it, ladies and gentlemen, 2029. Why do you say 2029 though? Is that because you feel that the energy, the research that we're at now, this cusp of what we're about to see, we've reached it, finally.

[00:05:17] Andrea Pfeifer: I think we have medication, medicines in development, which fulfill the requirements of safety, looking at the specificity of these pathological proteins. Predicting potentially the efficacy based on what we know from the antibodies, so we have learned all of that. So there are molecules now available, including ours, and what is even equally important is that we have now diagnostic means.

Because if you cannot, as George said, diagnose the people at risk, pre-symptomatic, when we have not achieved as much as we should to achieve the 60, 70, 80 percent of slowing of a disease, or if I could dream, prevent a disease.

[00:05:58] George Vradenburg: So what's so exciting here, Richard, is that these new active immunotherapies are actually in clinical trials today. J&J just announced in December, a major phase two trial of an active immunotherapy, tau targeting, developed by AC Immune licensed by J&J. But Andrea herself has vaccines in clinical trials.

And so that's why there's a merging sense of both we can do this and that they are safe. Because if you're going to immunize 100 million people around the world against Alzheimer's, which may be the volume we'd like to be able to do, you want to make sure that immunotherapy is truly safe. And we need if you're thinking of solving this disease globally, you have to have a very low cost, very easy to administer, very safe mechanism for doing so, and the world has gotten a great deal of experience with vaccines in pandemics and infectious disease, so the world has an experience of administering vaccines globally around the world. 

[00:07:02] Richard Lui: How does one benchmark fuel an another benchmark in this space? Because we have not had one in two decades.

So this, in the last couple of years, now with your research as well, is it all together happening? Is it random firings that are now coming together? How would you describe it for those who are not in the space of research that you're in? 

[00:07:25] Andrea Pfeifer: I think we are really at a crossroad between, symptomatic treatment and pre-symptomatic treatment, we're at a crossroad because we finally have the tools available for early diagnostic, which we didn't have.

We can now speak about precision medicine, and I'm coming from a cancer field. It took us years and years to reach this level, and there was definitely a breakthrough during the last two years in actually establishing even plasma and blood markers in order to predict who is at risk before clinical symptoms.

That's absolutely extraordinary. And that is the basis to link that to a safe and efficacious, active immunotherapy where you can actually provide maybe one shot, maybe two shots per year in order to prevent the disease. And just imagine if you could prevent this disease, what it would do in terms of social impact, in terms of economic impact.

And, you know, we are talking a lot about vaccination and all this different things, but there is a huge impact for society, for humanity. But just for economics, one patient costs 120,000 to 150,000 $ per year. If you could prevent each of that with a one shot of a vaccine, it would revolutionize the health system.

And finally, we would not speak anymore about the payers being willing or able to pay. It is affordable. 

[00:08:49] Richard Lui: Yeah, and one of the discussions certainly has been, and the two of you are right in the middle of it, is the chicken or egg when we talk about diagnostics versus immunotherapies, and I imagine now with the last year, on the diagnostic side, they're all going, this is great. We now have a market, because we can actually treat it. 

[00:09:06] George Vradenburg: Yeah, but right now, the market is PET scans, which are very expensive and very rare in the world, and neurologists, which are very rare and packed up. So right now, we've had Leqembi, the Eisai drug, on the market in the United States, and there are probably fewer than a thousand people on that drug, because of the backup there.

But I would say, your question about what is triggering this sense of optimism, is the fact the United States government policy, a regulatory policy and payer policy, demonstrates to people who want to invest in companies that there is a path to market. Now this drug, Leqembi drug, the one that just got approved this year, has now been approved, last year, you're right, 2023, now been approved in Japan and just two weeks ago in China. So this drug has now been approved for a population base of 2 billion people. And so that says to an innovator, that says to the big pharmas, that says to great biotechs like AC Immune, hey, there is a path to market here.

[00:10:07] Richard Lui: Talk about biomarkers and those who might be good candidates for these immunotherapies.

[00:10:13] Andrea Pfeifer: George mentioned already. Gold standard is still what we call the PET imaging, which is very expensive and not frequently available in particular in low and middle income countries.

And not even in countries like Switzerland, for example, you have it in every clinic. It's a very expensive methodology and it will remain the gold standard for some time for final diagnosis of patients. But before that, for recruitment purposes, inclusion criteria, etc., etc., there are now plasma and serum markers available and CSF markers, which allow you to do that faster and cheaper.

So, I have a big hope that we can expand what has been established in America and the sort of rich countries to the other parts of the country because there are these cheaper solutions. Now, this of course requires that you have also access to medication which is globally available and can be globally distributed.

[00:11:12] George Vradenburg: There are traditionally viewed amyloid and tau proteins in the brain that are viewed as the biomarkers for the disease. But now we're beginning to understand, that there are other, potential genetic biomarkers, and what's so exciting about the work that Andrea does is she's now working on alpha-synuclein biomarkers, alpha-synuclein vaccines.

So this means you can extend to other dementias, you can extend other things. So, she's got work in the Down's community, for example. So, this notion of precision medicine, because not everybody has the same mix of dementias as the next person, and particularly the Down's community has been one that we know that most Down's victims will eventually get Alzheimer's.

And here it is that we haven't been testing drugs in those people because we were so sensitive about them. 

[00:12:01] Richard Lui: So a perfect segue into good partnerships and collaborations. Tell us about what have been the most efficacious for you. 

[00:12:08] Andrea Pfeifer: Well, there are different dimensions, right? The private pharma partnerships and one of the partners we are working with now since quite some time and are launching the first prevention study with an active immunotherapy is Johnson & Johnson,

which has started last year, and it's the first clinical trial in a preclinical population, so presymptomatic population. It's a relatively large clinical trial with 500 patients we treat for four years. And we really want to prove a hypothesis that with such an active immunotherapy, you can actually stop the spreading and the seeding of what we call the tau protein.

So that's certainly one of them. But then there are other dimensions. I'm very much, appreciating the collaboration with George on the DAC. I was a little bit involved in the initial phase. Because I felt, in fact, I think the first meeting in Davos, we organized at WEF because I really, really strongly felt that Alzheimer's should be on the agenda of WEF.

It finally is, mediated, supported, driven by George and his people. So I'm super happy, so that's very important. And then there's also the CUI initiative and the CUI initiative has now vaccine group, which again, excites me a lot because we need global harmonization. We need to work with regulatory agencies,

we need to work with governments because the governments have to help us to implement what we have learned from COVID. And this is my biggest concern right now, how do we convince the different governments to actually almost update their national plans to include nationwide diagnosis, to include, registries so that we have actually access to this people. So that has to come. 

[00:13:53] Richard Lui: How do they do that? 

[00:13:55] Andrea Pfeifer: Not yet, but by talking to them. 

[00:13:58] Richard Lui: By talking to them. 

[00:14:00] George Vradenburg: Andrea referenced the global CEO initiative, which is sort of the corporate roundtable of the patient community. And that roundtable workgroup on vaccines includes eight companies. It includes four regulators from around the world, and it's going to include scientists, both basic scientists and clinical trialists, as well increasingly with payers. Because each one of those groups has got to say, this is a problem which we would like to solve together.

Each of us has a different role. Regulators have to approve the drugs, payers have to pay for the drugs. But there are issues at each stage of this. And as we know from our history with COVID, there's vaccine hesitancy, and whether people would adhere to a vaccine through time is in order to get the payoff Andrea described financially and economically and socially, this is going to take a team effort.

So from a patient's point of view, we want government, scientists, industry, and patients all to be at the table with a common goal with their different rules. 

[00:15:04] Richard Lui: With this new injection of interest in energy with, at least within the research community, how's that translated here at WEF this year, and the benchmark would be 2023 versus 2024. How would it compare?

[00:15:18] Andrea Pfeifer: You see more and more initiatives, you see more and more meetings taking place, more and more invitations also to me, for example, by private industries, by investors, etc., etc., by foundations. So I think there is a certain readiness to go to the next step, which is absolutely needed.

And by the way, the 2029 is only possible if everybody is on one table and we are all going in one direction. And COVID has shown it, in Alzheimer's we are not yet there. 

[00:15:46] Richard Lui: I was going to ask you what you look forward to, but I guess you're looking forward to 2029. 

[00:15:50] Andrea Pfeifer: Yes. and before. 

[00:15:53] Richard Lui: And before. Yeah, let's talk about the steps in between. Yes. 

[00:15:56] Andrea Pfeifer: No, but as George said, before we have the first readouts from our phase 2 clinical trial on the antiviral vaccine. So this would be if you like, the modeling of what has happened to the antibodies. And we see some readouts in Q1s, some readouts later in the year. And if they're positive, we can actually go straight into an accelerated development, which of course would assure the 2029 deadline.

And it's really what I'm focused on.

[00:16:22] George Vradenburg: I would say the next two years is going to be driving blood based plasma markers into the clinical field. So the doctors, even primary care doctors, begin to take blood tests and we can ascertain who is at risk for this disease. So that making things less expensive, more accessible and get more primary care.

Even community health workers that we work on in rural settings in Kenya can take blood tests. Or we're trying in Kenya to see whether you can do it with a saliva swab and get the same result. So we're trying to lower the cost, increase the accessibility of the means of screening, which are going to be essential to getting widespread use of innovative medicines.

[00:17:03] Andrea Pfeifer: And by the way, just to follow up on what George said, our vaccination or active immunotherapy needs exactly this information. We need to have access to this registry service, patients or people at risk in order to really do what we need to do, because we need to have large access to people with the risk of Alzheimer's. So the work, which is going on here in the community etc., etc., has to happen so that we can bring to a patient, prevention, of course, better quality of life. 

[00:17:37] George Vradenburg: I say one thing this year in Davos, is everyone's talking about the brain. And talking not just about suppressing disease, but how do you increase the capacity and resilience of the brain, because we now know increasingly that there is a great plasticity to the brain at all ages. And so prevention is now on the scale. How do we basically deal with all the risk factors associated with the future dementia? Cardiovascular disease, diabetes, obesity and lifestyle. And so that is on, so the whole notion of preventing disease that way, as well as how do you enhance brain health in employer settings by employers, by governments, how do we have national policies to regard brain as a brain capital item as something to invest in? In terms of expanding, everyone, there's a lot if you go up and down the street now in Davos, you see nothing but artificial intelligence.

We want to enhance Actual intelligence. 

[00:18:32] Richard Lui: That's what AI means, actually. Actual intelligence. 

[00:18:36] Andrea Pfeifer: Yeah, and if I just may add one point to this, my sort of hobby besides my real job is actually to really look into this non-pharmacological, as we call it, changes, which you can do, lifestyle changes, George mentioned it, in order to actually keep the brain health.

And I think we have to really start thinking how the pharmacological, so medication and non-pharmacological, work together and both together actually we enhance brain health. So that's really what we want to achieve. 

[00:19:05] Richard Lui: Where are we at from 1 to 10 as we finish up our conversation? If 10 is great and exactly where we want to go, and 1 is where we don't want to be at all, where are we?

[00:19:16] Andrea Pfeifer: I'll let George start. 

[00:19:18] George Vradenburg: I would say 2, but I can see 10.

[00:19:21] Richard Lui: You can see 10, okay. 

[00:19:23] Andrea Pfeifer: I would go maybe a little bit higher because, I see a lot of very good specific medication now coming up and the diagnostic field is being revolutionized. So maybe, I would go to a 3 or 4.

[00:19:37] George Vradenburg: Hope is the main logic. 

[00:19:38] Richard Lui: There you go. I'm totally with both of you on hope as well as real results. So Davos Alzheimer's Collaborative, great to be here at WEF as we sit here on the promenade here in 2024 with a great view on what we've seen in research recently and how to look forward to 2029. 

So thank you both. I really appreciate it. 

[00:19:56] George Vradenburg: Thank you, Richard. 

[00:19:57] Andrea Pfeifer: Thank you, thank you.

[00:19:58] Richard Lui: We'll see you next time.

[00:19:59] Dan Kendall: Thanks for tuning into the Brain Health News Podcast. Be sure to visit healthunmuted.com for more podcasts and information about brain health. Please also visit www.davosalzheimerscollaborative.org for more information about the work they're doing to shape the future of brain health on a global scale.