Lecanemab and Donanemab: Hype or Hope? An Essential Update

Lisa Skinner: 00:00:00

Hey, everybody. Welcome to a brand new episode of the Truth Lies and Alzheimer's show. I'm Lisa Skinner, your host. And as promised many times, I came across another new article about the Lecanemab and Donanemab. And I promised everybody that I would keep you updated on every bit of information I can share with you. And one of the reasons why I feel so strongly about keeping you informed is if we all can kind of reflect back on COVID. And all of the information that we received during the years that before the vaccinations came out. And it just seemed that, to me anyway, and this is my personal opinion, that we were being told what they wanted us to know, and what they wanted us to hear, regardless of whether or not it was accurate information or not. I personally would have preferred that if they didn't know something, they should have just been straight with us and transparent, and said, you know, we don't have all the information about this. But you know, we are feverishly working on it. But that never happened. It seemed like they were just making stuff up as they went along. And I think a lot of the information that we got during that period of time, was not always very accurate. And I don't want that to be the case for all of you on these, what they're calling Game Changer medications. Because every time I read a new update on it, it seems like the efficacy and the status of these drugs are changing significantly. So I'm sharing this with you today. Because I know some of you have loved ones out there who are on these medications, going through the infusions. And I want you to be informed on every thing new that comes out about it. So you can talk to your doctors about the information that comes out. All right, so this was written March 18 of 2024. And it's an article on big thing.com. And the title of this article to me, and this is what caught my eye is compelling. Don't buy the hype, a new breakthrough Alzheimer's treatments. That's the title of this article. Here we go. The sober reality behind the effectiveness of two new drugs touted as Alzheimer's breakthroughs, like Lecanemab, and Donanemab. These are the key takeaways, like beacons of light in the dark and I'm quoting two drugs have emerged over the past two years as the first disease modifying treatments for Alzheimer's disease. However, these drugs are expensive, complicated to administer, because we know now they do not penetrate the blood brain barrier and cause can cause dangerous side effects. Most importantly, numerous researchers think the drugs benefits will be imperceptible to patients and their families. So rather than grasping for a nebulous medical solution, many experts say it's better to focus on prevention. roughly 40% of dementia cases could be delayed or prevented by addressing lifestyle and environmental factors. This was written by Ross Pomeroy and he goes on to say the quest to find effective treatments for Alzheimer's disease has historically been a lost cause. We know this, a field littered with failed drugs and dashed hopes. According to a recent systematic review between 2003 and 2022. Researchers have tested 100 compounds against The devastating cognitive disease in phase one and three trials. Only two drugs made it through the rigorous gambit of pharmaceutical science. Their beneficial effects were too small to make a meaningful difference to patients. Then, like beacons of light in the dark. Two drugs emerged from phase three clinical trials as the first disease modifying treatments for Alzheimer's disease ECI and Biogen sulla Canna Mab burst onto the scene first, with data suggesting that it slowed cognitive decline by 27%. eli Lilly's Dinanath Mab followed with a more impressive result, slowly decline by 35%. scientists and journalists use words like breakthrough and revolutionary to describe these findings. Both drugs were given to older adults in the very early stages of Alzheimer's in trials lasting 18 months. A disease modifying treatment is one that delays slows, or reverses the progression of a disease by targeting its underlying cause until Lecanemab and Donanemab treatments for Alzheimer's only less than the debilitating symptoms, which include memory loss, paranoia, difficulty focusing, etc. These two drugs however, slow the disease's progression while removing aggregated clumps of misfolded beta amyloid proteins. Such plaques have long been theorized as a potential cause of Alzheimer's, as they are highly prevalent in three quarters of sufferers brains, first developing in areas that deal with memory and other cognitive functions. Just over two thirds of participants receiving Lecanemab actually had their brains effectively cleared of amyloid plaques. More than 80% of those given Donanemab did as well. But this is where the drugs start to lose their sheen. So listen to this, like Lecanemab and Donanemab removed the amyloid plaques get the Alzheimer's patients in the trials continued to decline. Remember, the drugs only slowed the disease, they did not stop it. This suggests that beta amyloid buildup is likely not the primary cause of Alzheimer's disease, hinting that the drugs overall effectiveness will be limited over the long term. Derek Lowe has worked on drug discovery for over three decades, including on candidate treatments for Alzheimer's. He writes sciences in the pipeline blog covering the pharmaceutical industry. amyloid is going to be has to be a part of the Alzheimer's story. But it is not cannot be a simple. amyloid causes Alzheimer's, stop the amyloid and stop the disease he

Lisa Skinner: 00:08:43

told big thing. Lowe is just one of many commentators who has also noted that the drugs beneficial effects would likely be imperceptible to family and friends. Data from the trials back those dour opinions. Although the effect of the drug will be described as being about a third, it consists on average of a difference of about three points on 144 Point combined scale of thinking and daily activities. Professor Professor Parrish Malhotra, head of the division of Neurology at Imperial College in London said of Donanemab , what's more, Lecanemab only improved scores by point four five points on an 18 point scale assessing patient's ability to think, remember and perform daily tasks. According to him, that's a minimal difference and people are unlikely to perceive any real alteration in cognitive functioning. That's a quote from Alberto s Bay at Professor of Neurology at the University of Cincinnati, College of Medicine, as he told kff health news. At the same time, these potentially invisible benefits come with the risk of visible side effects. Both drugs caused users brains to shrink slightly more over as many as a quarter of the participants suffered inflammation and brain bleeds and some very severely. Three people in the Donanemab trial actually died due to treatment related side effects. And then there's the steep costs with limited benefits, the time and costs associated with actually administering the drugs. Before taking one perspective, patients must receive a PET scan to look for amyloid plaques. They also must undergo genetic testing to confirm they don't have specific genes that would make them more susceptible to side effects. And once they start the treatments, patients require regular injections every two weeks for Lecanemab and every four weeks for Donanemab in a clinical setting. They also require frequent scans to watch for brain inflammation and bleeding. All of this takes time and money. The Institute for Clinical and Economic Review, tabulated the annual cost for Lecanemab, which is FDA approved by the way, they came to roughly $109,000 per patient per year included word the $26,500 list price, as well as costs for actually administering the treatment. These are done through infusion also convened a panel of 15 experts and ask them to assess the treatments value for the money. All 15 voted that the value is low. The Nano Mab has yet to receive FDA approval, but it should arrive this year. When it does. Experts expect the value to be similarly unimpressive. Medicare and Medicaid patients will comprise most of the market for the new treatments for Alzheimer's, so taxpayers and other beneficiaries will end up putting the sizable bill. But should a car called cost benefit analysis be the only way to analyze the Lecanemab and Donanemab in written comments to big think Chuck Dinnerstein medical director at the American Council on Science and Health presented a different perspective. While much has changed over the last few decades with respect to medicines tools. At some point, medical options are exhausted, and the physician can only offer one of our older tools, which is hope. The importance of Hope should not be underestimated. For those of a scientific bent, consider hope like a placebo, which works 30% of the time, these novel treatments undeniably constitute Alzheimer's patients best source of hope in decades. Patients and families will be pushing very hard to get this drug and they are not going to be objective when it comes to determining its value. Maybe mom has a few better days a month and can recognize you and chat with you for a few minutes. Dinnerstein added roughly 6.5 million Americans suffer from Alzheimer's dementia today. And that population is projected to double by the year 2050. So you can bet that many of them and their family members will consider $100,000 a pittance if it means slowing the disease even just for a few months. Will there come a time when treatments for Alzheimer's are clearly cost effective? There are many who thinks that Lecanemab and Donanemab collectively represent a solid start down that path. The success of these drugs is likely to spawn and guide years of subsequent research. Yale neurologist Steven Novella wrote at science based medicine, but others aren't so sure, again, these drugs target beta amyloid plaques, and they were very good at clearing them yet. The beneficial effects were compare Are Tim flea paltry? Some researchers say that we just have to get patients these drugs earlier and clear the plaques more quickly before they grow widespread. The hope is that very early treatment will slow progression enough that people will not live long enough to ever develop severe dementia novella wrote, This may lead to screening for Alzheimer's disease in asymptomatic individuals, especially if there is a family history. But lo is skeptical? That answer has been eroding as these trials have tried to catch people earlier and earlier in the disease progression. I honestly don't know what else you do give people the drugs before they're diagnosed with Alzheimer's. That's not going to be possible, he said. And what if the primary cause of Alzheimer's disease isn't beta amyloid? I think it's quite possible that the plaque hypothesis is backward. He says that the plaques are a result of something that has already happened to affect the brain not the cause of the disease. That was a statement that I quoted to you from Josh bloom, who's the director of Chemical and Pharmaceutical Sciences at ACS age as he told Big Think, if this is true, then it doesn't much matter what antibody or drug is used to dissolve the plaques, it's already too late.

Lisa Skinner: 00:16:50

It would be like trying to treat a wound by getting rid of the scab. Other theorized causes of Alzheimer's disease include tangles of another protein called tau, or possibly a viral infection. Unfortunately, I am not optimistic about any drug or antibody, putting much of a dent in this horrible disease. This is just too much that doesn't make sense about what's really going on Blum said, so, prevention versus treatment, rather than grasping for a nebulous medical solution. Many experts say it's better to focus on prevention. roughly 40% of dementia cases could be delayed or prevented by addressing lifestyle and environmental factors, according to a report published in The Lancet. And I actually read that report to you. Because I remember that statistic roughly 40% of dementia cases could be delayed or prevented by addressing lifestyle and environmental factors. These factors include exposure to air pollution, and excessive alcohol consumption goes on to say maintaining a healthy blood pressure might be the single best preventative measure. Researchers at Johns Hopkins have found that people using blood pressure medications lowered their risk by about 1/3. Moreover, studies suggest that learning a second language could delay the onset of Alzheimer's symptoms by five years on average, that relates to the parts of the brain that are used when you're translating one language to another. So very, very powerful brain activity and stimulation. The other thing I have researched is another, the other really powerful hobby you could take up that is as effective as learning foreign languages learning a musical instrument. So in conclusion, while treatments for Alzheimer's aren't that effective, yet numerous preventive measures are so there you have it. And again, I want you to be as absolutely informed on all the new information that's coming out on these drugs. So when if and when you do have this conversation with your loved ones, primary care physician, neurologist, whomever, and the topic of the Lecanemab or Donanemab infusions comes up you'll be equipped to ask really good questions to see if it's the right decision for you or your loved one. So I hope that this has been really helpful. I will keep you updated moving forward. As often as I run across these updates on these medications. It seems like the fingers are pointing directly at lifestyle choices so we can revisit that topic in upcoming episodes. I've done episodes on that in the past, I think maybe it's time to to do a recap on that modifiable risk factors non modifiable risk factors, lifestyle choices, so we'll be I'll be presenting that for you in the upcoming episodes so we can revisit that. I hope you all have a great week, and take good care of yourselves and your loved ones. And I will be back with another new episode of the truth lies in Alzheimer's show with your host Lisa Skinner next week. Bye bye