In this solo podcast episode, Lisa Skinner provides a detailed update on the recent FDA decision to delay full approval of the amyloid‑targeting monoclonal antibodies Donanemab, Aducanumab, and Lecanemab. She references a March 24 Guardian article and outlines the original hype surrounding these drugs, the clinical trial data (a modest 3‑point advantage on a 144‑point cognitive‑functional scale over 18 months), and the safety concerns that have emerged, including amyloid‑related imaging abnormalities (ARIA), brain swelling, hemorrhage, deaths in patients on blood thinners, and unexplained brain shrinkage. Skinner reports the high cost of treatment ($26,500‑$40,500 per year), the need for IV infusions every 2‑4 weeks, and extensive monitoring. She cites several experts—Timothy Daly, Sebastian Walsh, Ido Richard, and Ian Scott—who criticize the limited clinical relevance of the efficacy signals and question the focus on amyloid reduction. Daly also warns that the emphasis on drug solutions overshadows broader dementia‑risk factors such as social determinants and systemic oppression. Skinner concludes with practical advice for caregivers on how to discuss these medications with clinicians, encourages listeners to join her Minding Dementia support group, and signals that she will continue to monitor developments.
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Are you caring for a loved one with dementia? You don't have to figure this out all on your own. Welcome to Truth, Lies Alzheimer's, the show that helps you reimagine a new relationship with your loved one, a relationship a little more free of stress and anxiety. Join host Lisa Skinner and her 30+ years of experience as she guides you on a new path to a better relationship with those you care for. Here's Lisa.
Hi, welcome to another brand new episode of The Truth, Lies Alzheimer's Show. I'm Lisa Skinner, your host. And the information that I am bringing to you today is an update on some very controversial medications that we've been talking about. As a matter of fact, a couple of weeks ago, I shared another update with you on these newly approved drugs by the FDA. And since then, just a couple of days ago, there's been a new update on these drugs. It just came out on the 24th of March. In The Guardian, and the name of the article is Alzheimer's Breakthrough Stalls: Why a Much-Hyped Drug Is Facing Approval Delays. So I'm going to share this with you because it's really important to be aware of what they are telling us today. The benefits of drugs such as Donanemab, Akinumab, and Lecanemab are proving harder to quantify than its potential harms, is what the experts are now saying. It was heralded in news articles as a breakthrough, a turning point, a game changer for Alzheimer's disease. Some experts went so far as to call the drug Donanemab the beginning of the end. For debilitating condition. Well, that's all changed. Pharmaceutical company Eli Lilly in May of 2023 released data from a clinical trial they said showed Donanemab slowed cognitive and functional decline in people with early symptomatic Alzheimer's disease by 35%. Percent over 18 months. The findings saw the head of Alzheimer's Research UK and other experts call on drugs regulators to rapidly approve the treatment for use in patients. But despite reports the U.S. drugs regulator was set to approve Donanemab any day— you remember that? The Food and Drug Administration instead announced on March 8th that it has now delayed its decision to give full approval. The FDA said it wants an independent panel to further scrutinize data on the safety and efficacy of Donanemab, with a decision now expected later in 2024. The UK, European, and Australian regulators are also still assessing the drugs. In a statement, the executive vice president of Eli Lilly, Anne White, said, we are confident in Donanumab's potential to offer very meaningful benefits to people with early symptomatic Alzheimer's disease. It was unexpected to learn the FDA will convene an advisory committee at this stage in the review process, but we look forward to the opportunity to further present the trial results and put Donanemab's strong efficacy in the context of safety. She says. We will work with the FDA and the stakeholders in the community to make that presentation and answer all questions. Well, Dr. Timothy Daly, a dementia researcher from Sorbonne University in Paris, says this delay comes at no surprise to him. He says the benefits of Donanemab and similar much-hyped drugs, including Aducanumab and Lecanemab, have proved harder to quantify than their potential harms. Under this narrative of drug success, there are some really strong side effects, Daley told Guardian Australia. These are types of drugs known as novel monoclonal antibodies, and they target amyloid proteins in the brain. That we knew. Many researchers believe the buildup of these proteins contributes to Alzheimer's disease. But the drugs have been shown to reduce amyloid levels in the brain, but around 3 in 10 people taking lecanemab or donanemab in clinical trials developed a condition known as amyloid-related imaging abnormalities. The acronym for that is ARIA, A-R-I-A, a condition which can cause brain swelling and/or hemorrhaging. Mostly these seem to be minor, not come with any symptoms, and follow-up scans show they appear to have resolved, says Dr. Sebastian Walsh, who's a public health director, doctor researching dementia risk reduction with the University of Cambridge in the UK. In a small percentage of participants, it does seem to be much more serious, however. And there have been some deaths, particularly for those on blood-thinning type medications. Some trial participants also experienced brain shrinkage, and the long-term effects of that are still unknown. In the Donanumab trial, patients receiving the drug declined on average by 10 points on a 144-point scale that combined cognitive and functional scores. The placebo group, who were not receiving the drug, declined by 13 points. This data was used by researchers to state that the drug slowed cognitive and functional decline by more than one-third. That's only a 3-point spread. And offered people extra months or up to 1 year of life without further disease progression. Walsh says efforts to translate clinical data into terms more meaningful for people to understand means the effects of the drug have been overblown in media reports. Whilst it is understood that people want to think of other ways to present these numbers, it still needs to be scientifically valid, he says. Those who have reported it being an extra 6 months at higher function are on shaky ground scientifically, he says. These trials didn't measure recognition of a loved one. Ability to drive, any of these things, extrapolating in this way is not really justified by the evidence that they have actually proven. It's pure speculation, he says. A professor of neurology at Radboud University Medical Center in the Netherlands, Ido Richard, told news channel Al Jazeera, the drugs clearly remove amyloid proteins from the brain very successfully, but a reduction in amyloid proteins does not necessarily lead to a slowing of cognitive decline, he said. Research into the disease dating back more than 25 years has found that amyloid proteins are present in the brains of people with dementia. This has been proven through autopsy proceedings. But they are also found in people who don't have dementia and who never go on to develop it. Do you remember me telling you about the Nun study? It's my point. While many drugs trialed in the past have reduced amyloid levels, Donanemab Aducanumab and lecanumab appear to be the first to have also led a change in cognitive decline. But Richard claimed that change was statistically significant, but clinically irrelevant. That's a powerful statement. When the FDA approved aducanumab in 2021, 3 FDA advisory committee members who advised against its approval because of what they believed was a lack of efficacy data resigned. One of the people who resigned described it as probably the worst drug approval decision in recent history. When it came to implementation, The US health insurance program Medicare said it would not cover the drugs, and clinicians have also been cautious with little use of the drug. The Australian regulator, the Therapeutic Goods Administration, in June found, quote, there is no evidence of clinically meaningful efficacy of Aducanumab, end quote. As well as minimal meaningful clinical benefits from Donanumab, patients also need to receive the drugs via an intravenous infusion at a medical clinic or hospital every 2 to 4 weeks at a cost of about US dollars $26,500 or $40,500 a year, plus undergo regular testing. It is also a lot to ask of vulnerable people and their families. The other issue that was— has been brought up before is when it is administered intravenously, it has trouble crossing the blood-brain barrier. Barrier, and they've had to use ultrasound to open up that blood-brain barrier so these drugs can infuse properly. And that was just recently discovered. So they don't have the opportunity to be that effective because they can't cross the blood-brain barrier. It's not in this article, but I have quoted it from another article that I shared with you in the past. The director of internal medical medicine and clinical epidemiology at the Princess Alexandra Hospital in Queensland, Australia published a paper in the February edition of the journal Age and Aging with similar concerns. His name was Professor Ian Scott. He wrote, trials of amyloid-targeting monoclonal antibodies to date quote, do not provide high-quality evidence of clinically meaningful impacts at an affordable cost, end quote. Daley believes that significant focus on the potential of drugs that target amyloid buildup despite a lack of efficacy has been reductive, and it has seen less attention being paid to alternative hypotheses of what is causing the disease and a way to tackle it. Daley says that such findings make it tempting to list lifestyle changes for people that can make or, and reduce dementia risk. But he says this is also too simplistic as it puts the onus on the individuals rather than the government's. Working conditions, forms of oppression, and things that can't easily be seen as a dementia risk are just as important in preventing the disease, he says. There is an iceberg here. Don't just look at the surface at drugs and lifestyle. There are other living conditions and social structures that represent deeper contributions to risk in the population, and interventions targeting these are needed by governments to make our society fairer and more dementia resilient. Walsh says there is understandably a collective desperation among scientists and patients for better treatments and preventive options for Alzheimer's disease. Which is the most common cause of dementia in Western societies, but to date has no cure. But, he says, this cannot cloud objectiveness when we look at the evidence. So there you have it. That is quite a contradiction to what we have seen in the media more recently. I have shared that information with you on some of my shows. And this pretty much contradicts everything we have seen prior to this coming out this last weekend. So, quite disappointing. Quite disappointing. It's like, okay, back to the drawing board. And we were told that the FDA had given its full approval for these drugs. Sounds like they just— they rushed to a judgment where that's concerned. So I will definitely keep you all updated on these drugs because we were really hopeful that this was groundbreaking, that this was the hope we've been praying for for years and years and years. But I guess maybe The gun has been jumped a little too early. So anyway, I hope you found this interesting and valuable. And if the subject comes up with your doctor, you might have a good argument for prescribing these medications until they get this all figured out. All right. So I look forward to bringing you another new episode on the Truth Lies Alzheimer's show next week. Again, I'm Lisa Skinner, your host, and I hope you all have a wonderful, wonderful week. Take good care of you.
Bye-bye. Thank you for listening to Truth, Lies Alzheimer's. We hope you found something in today's episode that helps. We understand that caring for a loved one with dementia can be the challenge of a lifetime, but you don't have to do it alone. If you're ready for exclusive access to even more great content and resources, head on over to Facebook and join Lisa Skinner's Minding Dementia support group. We're a community of like-minded caregivers, and we're here to help.
