25.1 New Alzheimer's Drugs Are Deadly: Intro with Michael Shuman, PharmD

[00:00:00] Yeah, I mean, we're as an American public, what we're being sold is hope. Yes. Right? We're not being sold drugs that are proven to be effective. I mean, I'm talking about newer drugs, newly approved drugs. We're being sold hope. The pharmaceutical industry is preying on Americans hope. Somebody get this guy some help.

[00:00:34] Disclaimer. This podcast is for informational purposes only. The information provided in this podcast and related materials are meant only to educate. This information is not intended as a substitute. For professional advice. While I am a medical doctor, many of my guests have extensive medical training and experience. Nothing stated in this podcast, nor materials related to this podcast, including recommended websites, texts, graphics, images, or any other materials should be treated as a substitute for professional medical or psychological advice, diagnosis, or treatment. All listeners should consult with a medical professional, licensed mental health provider, or other health care provider if seeking medical advice, diagnosis, or treatment. Or put more simply. If you need help like this guy, call your own doctor. I am hyped tonight. We got Michael Shuman back. Really good to be back. I'm excited about this topic.

[00:01:03] Michael's been back several times and I think that we'll never run out of drugs to talk about. New drugs come out and there's new things to gripe about with them. Yep. And somehow they just keep getting approved, even when they don't work and they're not safe.

[00:01:19] But that's why we're here to talk to you about these things and really kind of an extension of direct to consumer advertising and the harms that it causes because you're giving information to the general public that really needs to be read with a fine tooth comb by people who have a lot of years of education tailored directly towards understanding medicine and pharmacology.

[00:01:47] And it just creates a situation that is very ripe for these companies to present things one way when in reality it is a much different picture of actual safety and efficacy. Yeah, there's one psychiatrist and I remember the time he even talking about a lot of what we call high level journal articles. The idea that some of them are just glorified advertisements.

[00:02:09] We have to have a level of discernment as we're looking through and assuming that these are produced as the ads are to generate income. And first and foremost, that is the goal. So we have to have that critical eye to make sure that we're looking to ensure that what we're being told is accurate and that it applies to the population in which we are intending to use it.

[00:02:31] Right. And one of the things that really got me, I mean, I've always I've been teed up on adacanumab in particular, the monoclonal antibody approved in 2021 for Alzheimer's disease. I've been keyed up on that for a long time. I mean, I've been railing against that for as long as I've been doing this podcast. Oh, I believe you. Yes.

[00:02:53] But in preparing to talk about adacanumab and its successors, lacanumab and donanumab, and in actually another podcast, it came to my attention in talking to Taylor Beckman, who is now in his cardiology fellowship down in Tennessee, about this 2022 science article that came out about a,

[00:03:15] neurologic or neurodegenerative disease lifetime researcher named Sylvain Lesney, who was found to have doctored or manipulated all of these images that in part laid the groundwork for the beta amyloid hypothesis of Alzheimer's.

[00:04:02] Wow. I was taught in medical school, you know, 10, 12 years ago. I was real about the fact that at least in academia, this time is replicating research is not a sexy thing. Nobody gets tenure because they say, hey, I'm going to check your work and make sure it's legit. But that is so important. If somebody has a recipe for doing something, you know, the example I always go to is looking at nitro press slide for schizophrenia. There's this big study out of Brazil in, I think, 2013.

[00:04:31] It came out right when I was starting into my faculty role, and that was the next big thing for schizophrenia. But finally, at that point, somebody tried to replicate it, and they couldn't. And so that kind of fell by the wayside because it was an amazing, groundbreaking paper. But if somebody else can't bake your recipes and this is the best cookies I've ever made, but nobody else can use that recipe, it's hard to trust that you actually got what you made from that. If we're not checking each other's work and ensuring that others can come to the same conclusion, we're putting a lot of trust in building everything from that foundation.

[00:05:01] And then if it turns out that one person had too much of a say, and then we find out later on that it's all built on the house of cards, it goes falling, and what are we left with? Right. People are probably getting annoyed at the repetition here, but the FDA is supposed to be that independent regulatory body. They should be replicating studies. Their budget should not be tailored to starting up a venture for a new drug. They should let the pharmaceutical industry handle that.

[00:05:30] Their job should be to independently try to replicate the findings of big pharma. And what they would find in the market today is that they're not able to replicate so many of the findings. We're going to talk about what are called monoclonal antibodies for Alzheimer's disease. Alzheimer's is the most common form of dementia, tends to affect people after the age of 65.

[00:05:57] But overall, it kind of progresses. One of the first kind of clinical signs symptoms that you tend to see revolves around short-term memory loss and dysfunction in what's called the hippocampus or the memory center of the brain. But it's very important to point out, and most people probably know this because a lot of us have seen or dealt with Alzheimer's in family members or certainly if you're in the medical community, you've seen it.

[00:06:26] It's a long and progressive disease. It's not something that typically kills somebody in a couple of years. It usually takes close to 10 years from the time the person is diagnosed. And really, probably from the time the process starts, probably closer to 20 years. So this is not something that is life-threatening in an acute time frame. And that's really important to consider for a couple of factors.

[00:06:53] One is if you have a drug that's not safe, I don't want my grandma to have a drug that'll cut the 10 remaining years of her life off at the potential benefit of adding maybe a few months or a year. And that's if she's the lucky one that gets that benefit versus one of the people who dies the second time they get an infusion of one of these drugs from a brain bleed or brain swelling.

[00:07:22] The other important consideration here is that these drugs, adacanumab, licanumab, donanumab, they all got accelerated approval. You're talking about accelerating the approval of a drug that we're not going to know whether it's effective or not for another 10 years.

[00:07:42] Because with a disease like Alzheimer's, you've got to have 10 or even 15 years worth of data on a drug to prove the most important outcome, which is how long somebody lives and how functional they are in the long term. You need that time frame to be able to prove that a drug for Alzheimer's works. This idea about functional outcomes is even a new thing.

[00:08:09] For years and years, that was not something that was regarding medications. Sadly, it is fairly new about using disability rating scales or looking at functional outcomes. The other thing I think that is important to notice about that is this is also a very emotional subject. And that's the one thing I think that sometimes we have to be careful of with some of these approvals. If this gives my loved one a chance, it's worth it.

[00:08:33] And so I think sometimes that emotional argument then maybe also gets people to buy into medications that even if there isn't the data, it's the idea is if this could work, I want it. Almost that you're treating the family, not the person is the idea that if we don't use this medicine, we're acknowledging we have nothing to do and we're acknowledging we can't fix this. And nobody wants to acknowledge that. So there's a let's at least try the medication.

[00:08:57] So I think those things then lead to maybe an acceptance of some of those risks you mentioned that kind of flies in the face of objective data. Yeah. I mean, we're as an American public. What we're being sold is hope. Yes. Right. We're not being sold drugs that are proven to be effective. I mean, I'm talking about newer drugs, newly approved drugs. We're being sold hope. The pharmaceutical industry is preying on Americans hope.

[00:09:28] Despite the emotional content, there is have a critical appraisal of, OK, you know, are there unintended consequences of giving into this hope, if you will? Yeah. And hopefully over the course of all the different examples that we bring up, our listeners or our viewers come to the conclusion that this is just continues to happen repeatedly. Repeatedly. We've got to stop falling victim to these essentially mind games.

[00:09:53] Now, I want to kind of give a brief introduction of some of the problems and then we'll kind of expand on those throughout our conversation. Michael mentioned the use of a surrogate marker.

[00:10:05] What that means is specifically for this class of drugs, a surrogate marker that allowed the adacanumab and lacanumab and donanimab to be FDA approved was the fact that all of these drugs have shown that they have the ability to remove a protein that is implicated as a potential cause of Alzheimer's called beta amyloid. And so this drug removes beta amyloid from the brain.

[00:10:35] The point that Michael and I are making is that the primary outcome should always be morbidity, mortality related. What would you say if I say I make the tastiest cake, we have a thousand participants to then test the cake. What should be the primary outcome? And they should probably like it. There should be some sort of enjoyment factor with this. Right. And so you could imagine that instead of taking the reports of a thousand people and calculating the data and saying, you know, this was the best cake.

[00:11:04] Instead, I just said, well, how many chocolate chips does each cake have on it? And the one with the most chocolate chips is going to be the best as determined by me. Right. Because we know that people like chocolate chips. So that is our surrogate endpoint for deliciousness. Exactly. So a drug removing beta amyloid, it's promising, but that theory is maybe not as sound as we thought.

[00:11:27] So adacanumab was approved by the FDA given this conditional or accelerated approval in 2021. It paved the way for lucanumab and donanumab to get the same type of approval. And this is notable for several reasons. One is that they only require one positive clinical trial in order to get this accelerated approval.

[00:11:52] And then they have to show after the fact, provide more data that the drug is safe and effective. But what it does is it buys them time. Then when their confirmatory trials shows what many scientists and clinicians were skeptical about in the first place, that the drug either does not work or is not safe, the company can just withdraw the drug from the market and either doesn't have to make the results of their confirmatory trial public,

[00:12:20] or they just don't really do a confirmatory trial. This drug was approved despite the FDA's own scientific advisory board voting 10 to 0 against it. There was one person who said that they were uncertain. There were three people of those 11 who resigned from the FDA board. It's also notable because of the manipulation of the way the data has been presented to Americans.

[00:12:48] Giving us this report of what's called relative risk or the difference that the drug shows compared to a placebo, as opposed to the absolute risk, which is typically what patients and what providers want to know. How much will this decrease my progression of symptoms over the time of the study? It's also extremely dangerous. These medicines, our first iteration of it, the adacanumab,

[00:13:18] was causing up to 40% of its participants to have brain swelling. And some of those develop brain bleeds, which can be fatal and have been fatal in the clinical trials. We'll talk a little bit about how this accelerated approval is being misused, something that maybe makes more sense for a condition like ALS,

[00:13:41] which is extremely severe, progressive in a rapid timeframe and universally fatal. And then we'll talk a little bit about, you know, primary outcome measures, secondary outcome measures. Does removing beta amyloid or tau protein actually improve cognitive symptoms? We'll touch on a bunch of different drugs. We'll talk about adacanumab and lacanumab and donanumab.

[00:14:08] But we'll also dive into some of the original research that laid the groundwork for these drugs even coming to market. We'll take a little brief pit stop on a drug called semufilam, another drug called presinezumab for Parkinson's disease, and also briefly touch on a drug for something called thalassemia,

[00:14:34] which can be a really severe blood disorder called deferaprone, as well as talk just a brief little bit about the statins, which are the drugs that were created in the 60s, I think, to help lower cholesterol. Yeah. So just a small little workload for tonight. Exactly. Exactly. A couple last little bits, you know, we're talking about meds that are extremely expensive.

[00:14:59] $56,000 a year for adacanumab when it came out, not covered by insurance. So that is primarily out of pocket. And the reality is these companies act like we have no effective treatments for Alzheimer's. And no, there's not something that reverses the course, even though I think that they kind of try to insinuate to the American public that this drug removing beta amyloid may reverse the progression.

[00:15:28] But the reality is that we're learning more and more about the pathology behind Alzheimer's every day. And something that big pharma or big hospital systems don't want you to know is there's a lot of things that you can do now that will drastically lower your lifetime risk of ever developing Alzheimer's disease. But they're not very lucrative. You know, I'm talking about things like vitamin D,

[00:15:57] things like a really healthy diet that doesn't have a bunch of processed food, that doesn't have a bunch of added sugar, good amount of physical activity, positive social interactions, other supplements or medications that reduce inflammation. And all of that is not even including the drugs that work just as well in terms of efficacy,

[00:16:22] donepezil and memantine for reducing or slowing down the progression of Alzheimer's that have been around for decades. And we know the safety profiles. We know that their side effect profile is nothing even close to major. Yeah. The other thing too is just simply from the pharmacist hat is the idea that we have so many medications we sometimes do use that are problematic. And sometimes the first step we can do is get rid of the other medications that are contributing to cognitive impairment.

[00:16:51] You know, we've talked about benzodiazepines in the past. It's in a number of patients I see who are on acetylcholinesterase inhibitor, but then also on an anticholinergic medication. So sometimes the first thing you do is get rid of the junk that's counterproductive, and then we can reevaluate where we're at. For their tardive dyskinesia? Oh yeah, or just for whatever, or for allergies or that, or for sleep. You know, throw any one of them. Everybody's on Cogentin. Yeah. It's like, oh, if I'm going to give you a dopamine blocking antipsychotic, I'm going to cover my ass.

[00:17:19] I don't know if this is just Louisville psychiatry or if it's national psychiatry. Oh no, it's been other places. That's one of my favorite things is, all right, can we lower the dose? It's been five days. Let's lower the dose. Let's make it PRN. Let's just get rid of it. Or we can use another antipsychotic. Oh my God. I mean, I cannot believe how many patients I saw in residency who were on a milligram of Cogentin twice a day in perpetuity. Yeah, the fact that you need that should be a clue you need to make a change. Yeah.

[00:17:44] Just for the background on that, Cogentin or Benztropine is a medicine that's extremely anticholinergic. In medicines that are anticholinergic or substances that are anticholinergic, they slow our brains down. In patients with dementia, they already have a balance between acetylcholine and dopamine that is thrown off. And when you add an acetylcholine blocker to that, you're going to get bad results.

[00:18:14] Their cognitive impairment is going to worsen in the temporary timeframe, if not the permanent timeframe, if they're on them long enough. Yeah. Things like delirium get thrown about. Sometimes it gets interchanged with dementia, even though they're totally different. But yeah, the idea is that we can do some addition by subtraction first. Before we go down the road of I need to use a pro-cognitive medication, let's at least get rid of the anti-cognitive ones. Right.

[00:18:38] Several months ago, a long-term patient of mine with prominent memory loss, but otherwise healthy, was attempted to be enrolled in one of the ongoing clinical trials for lacanumab, a medication approved for Alzheimer's dementia in the United States in 2023 due to its ability to remove beta amyloid from the tissue of the brain. With a faulty jump to the conclusion that this would translate into a clinical benefit of

[00:19:08] slowing the progression of Alzheimer's or even reversing its course. Unfortunately, not everything in science that theoretically should work actually works in clinical practice. But the drug industry and its regulators are increasingly preying on the hope and sometimes

[00:19:29] gullibility of the American public that technological advances will continually arrive with all benefit and no risk. That is certainly not the case with the three drugs approved through a non-traditional FDA pathway for Alzheimer's disease since 2021. Adicanumab or adju-helm, lacanumab or lakembi, and donanumab or casunla.

[00:19:58] Marketers even try to prey on people like me, who tout the need for us to find root causes of disease instead of just masking symptoms by labeling these drugs as disease modifying. Yes, they may modify the disease in a way that increases its progression to death in some. Beyond this alarming outcome, these beta amyloid removing drugs also do not outperform existing

[00:20:26] medications for dementia, therefore not offering much of anything outside of excess side effects and making Americans' wallets and bank accounts significantly lighter. I had already been on a crusade against the original 2021 accelerated approval of adicanumab as it was one of the sketchiest approvals in the FDA's history.

[00:20:51] It was approved despite the FDA Scientific Advisory Panel voting 10-0 against its approval, with three people resigning after the vote. It was approved despite an almost 2 out of 5 or 40% risk of brain swelling. And it was another clear indication that the FDA of today is essentially a subsidiary of Big Pharma.

[00:21:19] But when you start fucking with my patients, putting them at risk for severe side effects and death, when they not only have 10 plus years of life left to live, but also years of functional life left, that really grinds my gears. Honestly, it pisses me off. You don't have to be some devout theologian to see that it's just not right.

[00:21:49] And if non-medical persons have access to this information, presented in a way that they can understand, they'll also realize it's not right. Little did I know that the corruption goes much deeper than the bullshit accelerated approvals of lacanumab and adacanumab for a condition that is mostly preventable and people can live with for more than 10 years.

[00:22:14] There is also rampant evidence of manipulated research going back decades with some of the most prominent names in neurodegenerative research's work being called out for manipulating and faking some of the research that paved the way for the eventual development of these dangerous drugs. What are we doing to ourselves in this country? Or better said, what are we allowing our regulatory bodies

[00:22:44] and the businesses they're supposed to regulate do to us? We're given highly processed food with boatloads of added sugar, taught to fear anything and anybody that may be different than us through our news media. We're addicted to everything from our phones to our prescriptions, to our Netflix, to meth and fentanyl. And act like the structure of our society doesn't have anything to do with us having 20% of the world's overdose deaths,

[00:23:14] despite constituting less than 5% of the global population. All of these and so many more create vicious cycles of inflammation from our guts to the fear, anxiety and memory centers of our brains. Inflammation drives this inability to clean out our systems and eventually overt diseases like Alzheimer's invade.

[00:23:42] Then, once we have the disease, our only hope for a way out involves some miracle cure that does not exist in reality, that will bankrupt us. The classic Ponce de Leon story in his unascertainable quest to find the so-called fountain of youth. Luckily, my patient had me to educate them on the dangers associated with these drugs.

[00:24:12] They did not fall victim to the potential side effects of missing out on plenty of good times and experiences with their families and friends over the next 10 years. But I fear so many others may not be properly educated on how this system works and who it preys upon. That's why this series is so damn important to me. I cannot watch the same movie play out again and again and again

[00:24:42] from Oroflex to Oxycontin to Vioxx to Makenna to Deferoprone. The list of drugs that have promised cures or incredible results at little to no side effect cost is seemingly endless. The definition of insanity is letting history continue to repeat itself, doing that same thing over and over again.

[00:25:11] We've got to do something different. This, outside of my direct clinical practice, is how I try to move the needle. We've got to stop being victims. We've got to educate ourselves so we can stop participating in a system of direct-to-consumer advertising that is killing Americans every year while it promises that it's helping them. I hope you enjoy this series, but even more so,

[00:25:41] I hope you do something about this. Talk to somebody about it, not in a demeaning or a demonizing way, but from a place of caring, from a place of love for humanity and people, regardless of who that somebody is, what that somebody looks like, or what that somebody stands for. We are being duped. We are dying earlier in more frail conditions, even though these supposed technological advances

[00:26:11] and disease-modifying therapies promise longer and more vigorous lives. Join me in this intellectual and scientific fight to get back to promoting progress over profits in science. Buckle up for a month's worth of discussions on these new drugs and the research and the faulty research that paved the way for their approvals. Hope you enjoy.

[00:26:41] Thanks again for watching and or listening. If you're passionate about the subjects that I discuss on the channel, do me a favor and like, comment, subscribe. Do whatever you can to make your voice heard that these are problems that must be addressed in our society. If you have any questions, comments, or concerns, I want to hear them. Feel free to reach out on social media

[00:27:10] or email us at renegadesyke at gmail.com. And if you'd like to be a guest of the show or you have a connection to somebody that you think would be a good guest, let us know. Thanks again for listening.