Whoops, not for me. With my damaged brain already running with millions to billions less neurons I'll pass on more brain shrinkage.
YIKES! FDA Approves Lecanemab Against Alzheimer’s
For decades the news about Alzheimer’s disease [AD] has been dismal. No medication has been shown to actually delay or reverse the symptoms of AD. The FDA gave the latest anti-amyloid drug, lecanemab (Leqembi), accelerated approval status. Many neuroscientists have hailed this drug as an important advance against dementia. The media has made it seem as if the drug is a breakthrough.
Anti-Amyloid Drugs and Brain Shrinkage?
But there is a new and disturbing fly in the ointment. A study published in the journal Neurology (March 27, 2023) reveals that anti-amyloid drugs like lecanemab can cause brain shrinkage. The researchers call this accelerated “brain atrophy.” Such a reduction in brain volume is usually linked to worsening dementia.
We reported this unexpected complication after reading an article in Science (Dec. 7, 2022) titled “Brain Shrinkage As A Side Effect.” The author refers to an article in STAT (Nov. 29, 2022) titled “Anti-amyloid drugs and the mystery of treatment-associated brain shrinkage.”
The neurologist who wrote this article works at the National Institute on Aging. He was reporting on early Phase II clinical trials of lecanemab:
“The acceleration of brain shrinkage — also known as atrophy or reduction in brain volume — has been described in clinical trials of other anti-amyloid antibodies, including aducanumab (now FDA-approved as Aduhelm) and donanemab. It’s important to fully understand this phenomenon and its long-term implications, because in people with Alzheimer’s disease, brain shrinkage, typically measured on MRI scans as a reduction in brain volume or an increase in the volume of the brain’s fluid-filled spaces (known as ventricles), has been consistently associated with progression of the disease rather than slowing of symptoms.”
Researchers often perform autopsies on patients diagnosed with AD. That’s because the best way to prove someone actually died of Alzheimer’s disease is to look at the brain. Brain shrinkage can be measured by looking at ventricles. The bigger the ventricles the more atrophy there is in the brain. As shrinkage increases, AD tends to get worse (Brain, Sept, 2008).
A Systematic Review and Meta-Analysis of Anti-Amyloid Drugs:
The most recent study comes from scientists at the Institute of Neuroscience and Mental Health at the University of Melbourne, Australia (Neurology, March 27, 2023). They reviewed brain volume changes after patients were exposed to anti-amyloid drugs.
The authors analyzed data from 31 clinical trials of 14 anti-amyloid drugs. Both aducanumab and lecanemab were included in the analysis. The results of the study are startling! The researchers report that their data:
“…reveal the potential for anti-Aβ [amyloid beta] therapies to compromise long- term brain health by materially accelerating brain atrophy and provide new insight into the adverse impact of ARIA [Amyloid-Related Imaging Abnormalities].”
The authors note that all of the drugs that reduce amyloid in the brain cause detectable “imaging abnormalities.” In other words, the structures within the brain are changed and not necessarily in a good way. As they report:
“…loss of brain tissue is the proximate cause of cognitive dysfunction in AD and volume changes are supportive and objective evidence of disease progression.”
There are many unanswered questions about anti-amyloid drugs and the long-term benefits or risks of such medications. The authors of this research call for drug companies to release data from clinical trials so that other investigators can analyze the impact of brain shrinkage on clinical outcomes over time.
How Effective Are Anti-Amyloid Drugs Like Leqembi?
A lot depends upon how you define “effectiveness.” Drug companies and the FDA probably define drug effectiveness differently than you do.
Most of the news articles about the Leqembi emphasize that it “modestly” slows the decline of mental deterioration. What exactly does that mean and why did the FDA grant this drug “accelerated approval” status?
Accelerated Approval?
The FDA has a special category for drugs that might help hard-to-treat conditions.
It describes the process this way:
“The FDA instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and fill an unmet medical need based on a surrogate endpoint. A surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit but is not itself a measure of clinical benefit. The use of a surrogate endpoint can considerably shorten the time required prior to receiving FDA approval.”
There is a huge problem with surrogate endpoints, though. Modifying them with a drug does not always produce the desired clinical outcome.
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