Oh, No! FDA Delays Approval of Donanemab, Aducanumab, and Lecanemab: Discouraging Update

Lisa Skinner: 00:00:00

Hi, welcome to another brand new episode of the truth lies and 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 Diana Mab, hakuna Mab, and Locanda Mab 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 don't Anna Mab the beginning of the end for debilitating condition. Well, that's all changed. Pharmaceutical Company Eli Lilly in May of 2023. Release data from a clinical trial they said showed dinamika Mab slowed cognitive and functional decline in people with early symptomatic Alzheimer's disease by 35%. 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 US drugs regulator was set to approved banana Mab any day you remember that the Food and Drug Administration FDA instead announced on March eighth that it is 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 Diana Mab. 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 and White said, we are confident in banana maps 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 dynamap 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 de nada Mab and similar much hyped drugs including Abu Cana Mab and Locanda mob, have proved harder to quantify than their potential harms. Under this narrative of drug success, there are some really strong side effects daily 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 believed the buildup of these proteins Is contributes to Alzheimer's disease. But the drugs have been shown to reduce amyloid levels in the brain, but around three in 10 people taking Locanda Mab or de Nonna Mab 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, Dr. 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 denominator trial, patients receiving the drug declined on average by 10 points on 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 drugs slowed cognitive and functional decline by more than 1/3. That's only a three point spread and offered people extra months or up to one 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 six 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 RAD bound 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. Well, many drugs trialed in the past have reduced amyloid levels the anonymous addict can imagine and Locanda Mab appear to be the first to have also led a change in cognitive decline. But Richard claimed that change was statistically significant. But when nicly irrelevant, that's powerful statement. When the FDA approved as you can imagine, in 2021, three FDA advisory committee members who advised against its approval because of what they believed was the lack of efficacy data resigned.

Lisa Skinner: 00:09:54

One of the people who resigned described it as probably the worst First 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 ad you can imagine and quote, as well as minimal meaningful clinical benefits from banana Mab. Patients also need to receive the drugs via an intravenous infusion at a medical clinic or hospital every two to four 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 a vulnerable people and their families. The other issue that was was has been brought up before is when it is administered intravenously. It has trouble crossing the blood brain 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. That'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 and quote, Daly 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. Daily 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 form several pression. 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. Wall 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 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 again, 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 and 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