This series of bite-sized episodes contains important information you need to navigate the evolving world of Alzheimer’s disease (AD) research. Dr. Marc Agronin and Dr. Richard Isaacson discuss the recent advances in AD and provide practical approaches for prevention, diagnosis, and treatment.
What Is Immunotherapy?
Advancing Alzheimer’s Disease
What Is Immunotherapy?
What Is Immunotherapy?
What Is Immunotherapy?
Welcome to CME on ReachMD. This episode is part of our MinuteCME curriculum.
Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements as well as the learning objectives.
This is CME on ReachMD, and I'm Dr. Marc Agronin. I'm here today with my colleague Dr. Richard Isaacson.
Dr. Isaacson, there's been a lot of talk about disease-modifying treatments for Alzheimer's disease, more specifically, what we call immunotherapy. Can you tell us in general, what is immunotherapy? How did it start? Where are we going? And let's have a good discussion about what's going on now with these particular treatments.
Sure. So immunotherapy targets specific pathologic proteins that build up in the brains of people with Alzheimer's. And the anti-amyloid antibodies have been developed over decades now, believe it or not, decades. There's a variety of them from solanezumab to gantenerumab to aducanumab, donanemab, lecanemab, there's just many, many. And basically, these drugs are given usually through the IV and given over a long period of time and target amyloid and try to reduce amyloid buildup in the brain. And then you can actually track amyloid and track cognitive function to try to understand whether these drugs may or may not be effective.
Now, in terms of the history of these anti-amyloid drugs and immunotherapy, in the past, decades ago, when people got the drugs, we actually didn't have a biomarker to test for amyloid, so people with a clinical diagnosis of Alzheimer's were getting these anti-amyloid drugs. And some people may have had an effect and other people didn't. But when we ended up looking at the data later, when the Alzheimer's biomarkers came to fruition, many of these people, you know, 20%, 30%, 40% – up to 40% in some studies – people didn't even have amyloid, so the targeting of the anti-amyloid drug really wasn't the right thing to be done in that patient.
So basically, where the field is gone is to do an assessment, does the person truly have amyloid, and then we can deploy an immunotherapy, either in monthly or bimonthly infusions, or also sub-Q injections that were also studied but didn't come to fruition just yet. And then basically, people can be followed through their cognitive function, their PET scans, and then, you know, once their amyloid is low or gone, maybe then we would stop these drugs. And it's, you know, these are really important questions.
So that's a general overview. But, it's really been quite a field and a lot of developments, including 1 that was FDA-approved within the last year and then 2 that have been submitted to the FDA.
Sure, and now we've also been researching anti-tau immunotherapy as well. The question over time will be, do we do one or the other? Do we do both? And that's where research is heading.
The controversy comes in as is that we aren't seeing people even when there's a significant reduction of amyloid, as an example. We're not seeing people getting better. But we are seeing, in general, a slowing of the disease process. And so really leads to this question of what's a meaningful outcome for this? And we're seeing with data that there's variability in terms of who's getting it, what is their genetic background? What dosing are they getting? So for instance, with aducanumab, which, garnered an FDA approval, we know that with especially certain individuals, who are getting the higher dose, had a significant slowing and their disease course. And so the question is, how do we track that over time? When we roll these out in terms of actual market products, how does that play out? We need to educate people in terms of the role of these. So exciting developments. And, Richard, where do you think we're heading with these treatments?
Yeah, I think we're headed to kind of a new frontier where these drugs, you know, some people may think they're, you know, terrific, and they're great. And other people say, “Oh, they only slow decline by 27% over a period of time; that's not really worth it.” Well, you know, I think patients and their physicians need to really have these honest discussions. And you know, these drugs can be expensive, they're time consuming. There are also safety issues, which need to be kind of monitored. But, you know, I think whether one believes that X period of slowing of decline versus Y, I think there’s going to be a lot of learning that needs to be done. I also think we're entering an area of personalized medicine where different people with different genes are going to have higher or lower likelihood of side effects. So I think personalized medicine in Alzheimer's is now arriving. And I'm excited for the years to come with these therapies.
Sure, I agree with that. I guess one key takeaway that we tell individuals is that, especially if there's early symptoms of what may be Alzheimer's disease, to get a comprehensive diagnosis and then explore whether immunotherapy is an option, either through a clinical trial or through an agent that's on the market. But if there's an opportunity, especially in an early stage, to slow this disease down, that can make all the difference over time.
So this has been a brief but a great discussion. Unfortunately, our time is up. To everyone, thank you for listening.
You have been listening to CME on ReachMD. This activity is provided by Prova Education and is part of our MinuteCME curriculum.
To receive your free CME credit, or to download this activity, go to ReachMD.com/Prova. Thank you for listening.
Disclosure of Conflicts of Interest
In accordance with the ACCME Standards for Integrity and Independence, Global Learning Collaborative (GLC) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any ineligible company. GLC mitigates all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational programs.
Marc E. Agronin, MD
Senior Vice President, Behavioral Health
Chief Medical Officer, MIND Institute
Miami Jewish Health
Consulting Fees: Eli Lilly and Company, Otsuka America Pharmaceuticals Inc.
Contracted Research: AgeneBio, Alzheon, Inc, Avanir Pharmaceuticals, Inc, Eli Lilly and Company, F. Hoffman La-Roche Ltd, Janssen Global Services, LLC, Sage Therapeutics, Inc.
Richard S. Isaacson, MD
Director, Center for Brain Health
Florida Atlantic University
Boca Raton, FL
No relevant relationships reported.
- Cindy Davidson has nothing to disclose.
- Amanda Hilferty has nothing to disclose.
- Nick Lombardi has ownership interest in Vertex Pharmaceuticals.
- Libby Lurwick has nothing to disclose.
- Colleen Resnick has nothing to disclose.
After participating in this educational activity, participants should be better able to:
- Contrast how the slowing of Aβ plaques, as shown in recent clinical trial endpoints of slowing cognitive decline with immunotherapies, differs from current standard of care results in Alzheimer’s disease (AD)
- Recognize the positive impacts of earlier identification of AD in slowing the course of the disease
- Analyze how the mechanisms of action of newer investigational therapies relate to the molecular mechanisms that drive AD progression
- Analyze biomarkers for functional impairment, neuronal loss, and protein deposition that are assessable by neuroimaging or cerebrospinal fluid analysis for diagnosis, staging, and treatment outcomes
- Compare the monoclonal antibodies currently under study to treat AD
- Evaluate new agents that may be appropriate for patients with mild cognitive impairment (ie, the role of imaging)
This activity is designed to meet the educational needs of neurologists, primary care physicians, and other healthcare professionals that diagnose and treat patients with Alzheimer’s Disease.
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Global Learning Collaborative (GLC) designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
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