Ever since the FDA approved the first anti-amyloid Alzheimer’s drug Aduhelm (aducanumab) on June 7, 2021, there has been a firestorm of controversy. The FDA’s own expert advisory committee voted against approval. The drug company voluntarily withdrew the drug from the market on November 1, 2024. The FDA went on to approve two other anti-amyloid Alzheimer’s drugs in 2024: Leqembi (lecanemab) and Kisunla (donanemab). I have asked a question about such drugs: Breakthrough or Boondoggle?
The New York Times Cracks the Case Wide Open:
On October 23, 2024 Walt Bogdanich and Carson Kessler wrote an amazing article in the New York Times titled:
“What Drugmakers Did Not Tell Volunteers in Alzheimer’s Trials”
This is an extraordinary article. If you do not have access to the New York Times, here is the essence of the investigative journalism.
People who are especially susceptible to Alzheimer’s disease have a gene variant known as APOE4. It is not surprising that pharmaceutical companies would want to test their anti-amyloid Alzheimer’s drugs on people who are at higher risk for this disease. That’s because a high-risk population is more likely to demonstrate benefit from a medication in a shorter period of time.
The NYT article describes the Eisai study of Leqembi:
“In its trial protocol, the company specified that it wanted participants already experiencing mild cognitive decline. ‘No less than 70 percent’ would have the APOE4 gene. Carriers were known to face a higher risk of brain injuries, especially those with two copies.”
And that is the crux of the problem. The company was seeking participants in its clinical trial who were genetically vulnerable to dementia. But, people with the APOE4 gene were also at greater risk for microhemorrhages in the brain while taking anti-amyloid Alzheimer’s drugs. Such brain bleeds are not a good thing.
According to the NYT investigation, the company did not share the genetic information that would alert patients to their higher risk for bleeding while taking the medicine.
The authors of the article went on to state:
“This past July, the agency approved a second, similar drug, Kisunla. In a clinical trial, its maker, Eli Lilly, also chose not to tell 289 volunteers that their genetic profiles made them vulnerable to brain injuries, The Times found. Dozens experienced what Lilly classified as ‘severe’ brain bleeding.”
Clinical Trials and Secrecy:
I have participated in a clinical trial myself. Although I certainly wanted to know my test results, the researchers told me in no uncertain terms that the data was privileged. That is to say, it was a deep, dark secret.
If you get your blood drawn or your doctor orders some other test, you will probably be able to access that data promptly on a website. If, on the other hand, you are part of a clinical trial, the chances are good that your personal data are going to be unavailable, not just during the trial but even after the overall data are published in a journal.
There is a movement that was initiated by my friend “e-Patient Dave” aka Dave deBronkart. It is called:
“Gimme My Damn Data (and Let Patients Help!)
Here is a link to that article in JMIR Publications. And here is a video with e-Patieint Dave singing the Damn Data theme song.
As far as the trial I was involved in, the investigators would have access, and the drug company would have access, but the participants were kept in the dark. I found that beyond disappointing. You might call it outrageous. But it is not unusual.
Anti-Amyloid Alzheimer’s Drugs:
In the case of the two drugs being studied against Alzheimer’s disease (AD), the patients with an APOE4 gene vulnerability to brain bleeds were not told that the medicines being tested could be extra dangerous for them. The article in The Times reveals heart-breaking stories of patients who died after receiving the anti-amyloid Alzheimer’s drugs.
If these medicines were actual breakthroughs against AD, the risk might have been worth it. But as you will read in our articles below, the potential benefits are small at best. These drugs do not reverse dementia.
They do not allow people to resume work. Patients do no better at remembering family members, balancing their checkbooks or avoiding nursing homes. The medicines slow the decline a little bit for awhile. Worth the risk? That’s up to individuals and their families.
One More Problem with Anti-Amyloid Alzheimer’s Drugs:
There is one other complication that most people are totally unaware of when it comes to the anti-amyloid Alzheimer’s drugs. It is what I have described as brain shrinkage or brain atrophy. I wrote about “Anti-Amyloid Drugs and Brain Shrinkage?” in this article:
YIKES! FDA Approves Lecanemab Against Alzheimer’s
If you take a moment to read this post you will discover that researchers discovered this problem a few years ago Science (Dec. 7, 2022). I was especially concerned about a systematic review and meta-analysis published in the journal Neurology (May 16, 2023). It was titled:
“Accelerated Brain Volume Loss Caused by Anti-β-Amyloid Drugs”
The New York Times article notes that:
“Brain atrophy comes naturally with aging, but it occurs faster in Alzheimer’s patients and faster yet in patients on amyloid-lowering drugs, according to neurologists.”
The authors quote Professor Scott Ayton. He is the Director of the Centre of Research Excellence in Enhanced Dementia Diagnosis (CREEDD) and head of the Dementia Mission and the Translational Neurodegenerative Group in the Florey Department of Neuroscience and Mental Health at the University of Melbourne, Australia.
He told The Times:
“‘The shocking results that came from our analysis,’ he said in an interview, ‘is that these drugs, in every class that we looked at, did not preserve brain volume — they accelerate the apparent shrinkage.’”
An Inconvenient Truth: Brain Shrinkage with Anti-Amyloid Alzheimer’s Drugs:
We have been bugging the FDA about this problem for a long time by contacting executives at the agency. So far, we have heard crickets in response to our inquiries. We do not know what the long-term prospects are for these anti-amyloid medications. To date, we have been unimpressed.
We desperately need better, safer drugs to reverse Alzheimer’s disease. And they need to be made available at an affordable price.
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