FDA approves first at-home starting dosage for subcutaneous lecanemab in Alzheimer’s disease

 

Whoops, lecanemab is not for me. With my damaged brain already running with millions to billions less neurons I'll pass on more brain shrinkage. But I'm not medically trained so don't listen to me.

From this article comes the following paragraphs:

YIKES! FDA Approves Lecanemab Against Alzheimer’s

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.” 

And this from the article means more reason not to do this. Caution is also advised for patients using anticoagulant medications because of an increased risk of intracerebral haemorrhage.

FDA approves first at-home starting dosage for subcutaneous lecanemab in Alzheimer’s disease

The US Food and Drug Administration (FDA) approved a new starting dosage regimen for the subcutaneous (SC) formulation of lecanemab-irmb (Leqembi IQLIK) for adult patients with Alzheimer’s disease. This approval allows individuals to begin treatment via home administration by themselves or a caregiver, marking a significant update from the previous requirement for an intravenous (IV) starting dosage.

Lecanemab-irmb is an amyloid beta-directed antibody indicated for patients at the mild cognitive impairment or mild dementia stage of Alzheimer’s disease with confirmed amyloid pathology. Before this decision, the SC formulation was only authorised as a maintenance option for patients who had already completed 18 months of IV therapy.

Although the SC formulation was not evaluated in separate large clinical outcome trials, its approval was supported by evidence demonstrating that it produced equivalent results in the body and similar reductions in amyloid plaques compared with the IV formulation.

Common side effects include headache, infusion-related reactions, and amyloid-related imaging abnormalities (ARIA). ARIA is a known side effect of amyloid-targeting antibodies and typically presents as temporary brain swelling or small spots of bleeding. While often asymptomatic, ARIA can lead to headache, confusion, dizziness, and nausea, and may infrequently cause life-threatening brain oedema.

The prescribing information includes a boxed warning regarding ARIA risks. The FDA noted that patients homozygous for the ApoE ε4 allele have a higher incidence of serious ARIA compared with heterozygotes and non-carriers. Consequently, testing for ApoE ε4 status should be performed before initiating treatment.

Additional adverse reactions associated with SC administration include injection-site reactions such as redness, swelling, and pain. Caution is also advised for patients using anticoagulant medications because of an increased risk of intracerebral haemorrhage.

The approval was granted to Eisai under a priority review designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

Reference: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-home-starting-dose-alzheimers-disease-treatment 

SOURCE: US Food and Drug Administration

Alzheimer’s Drug Reduces Amyloid but Fails to Restore Brain Waste Flow

 

Whoops, lecanemab is not for me. With my damaged brain already running with millions to billions less neurons I'll pass on more brain shrinkage. But I'm not medically trained so don't listen to me.

From this article comes the following paragraphs:

YIKES! FDA Approves Lecanemab Against Alzheimer’s

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.” 

Alzheimer’s Drug Reduces Amyloid but Fails to Restore Brain Waste Flow

Summary: Researchers found that lecanemab, the Alzheimer’s drug designed to clear amyloid-β plaques, does not improve the brain’s waste clearance system in the short term. In a three-month study using MRI-based DTI-ALPS imaging, scientists observed no measurable recovery in glymphatic function after treatment.

This suggests that once neuronal and clearance system damage occurs, it may be too advanced to reverse quickly. The results emphasize the need for multi-targeted strategies to address Alzheimer’s disease beyond amyloid reduction alone.

Key Facts

• Study Finding: Lecanemab reduces amyloid-β but doesn’t restore glymphatic waste clearance after 3 months.
• Implication: Short-term therapy may not repair established neuronal damage in Alzheimer’s.
• Future Direction: Research will assess long-term effects and age-related factors influencing treatment outcomes.

Source: Osaka Metropolitan University

A group from Osaka Metropolitan University in Japan, led by graduate student Tatsushi Oura and Dr. Hiroyuki Tatekawa, found that treatment using the drug lecanemab to remove amyloid plaques in the brain does not change the waste clearance function in the brains of Alzheimer’s disease (AD) patients in the short term.

This suggests that even after treatment, the AD patients’ nerves are already damaged, and the waste clearance function does not recover in the short term. Their findings show the complexity of the disease and the need to address multiple disease-causing pathways simultaneously in the future.

Their findings add to the complicated process of unraveling AD’s mechanisms. Despite being the most common form of neurodegenerative disease, it is tricky to treat because of its multiple causes.

One cause of the nervous damage common in AD is the accumulation of the protein amyloid-β (Aβ) in the brain. In healthy patients, the glymphatic system moves cerebrospinal fluid along the spaces around the arteries into the brain tissue, where it mixes with interstitial fluid to carry away metabolic waste like Aβ. This is called the ‘glymphatic system’ after the glial cells involved in the process.

However, in AD patients, Aβ builds up, stiffening arteries and reducing the flow from the brain to the cerebrospinal fluid. This blockage triggers a chain of neurodegenerative processes, leading to AD symptoms.

The recently approved therapeutic lecanemab reduces accumulated Aβ. The team from the university’s Graduate School of Medicine evaluated the glymphatic system before and after treatment in patients who received lecanemab therapy, using the DTI-ALPS index.

Contrary to expectations, they found no significant change in the index between pre-treatment and 3 months after treatment.

They concluded that although anti-amyloid therapy can reduce plaque burden and slow further cognitive worsening, it may be insufficient to restore lost function. This suggests that neuronal damage and clearance system deficits have already been well established by the time the patient starts showing symptoms. Their findings show the range of factors involved in the progression of AD, many of which are not easily reversible.

“Even when Aβ is reduced by lecanemab, impairment of the glymphatic system may not recover within the short-term,” Oura said.

“In the future, we want to look at factors like age, the stage of the disease, and degree of lesions in the white matter to further understand the relationship between changes in the glymphatic system due to lecanemab treatment and the outcome of treatment. This will help understand the best way to administer treatment to patients.”

Funding: This study was supported by the Takeda Science Foundation (ROR ID: 02y123g31) and Japan Society for the Promotion of Science (JSPS) KAKENHI (grant number: 25K19115). Data were obtained from the OASIS (OASIS-3, Longitudinal Multimodal Neuroimaging: Principal Investigators: T. Benzinger, D. Marcus, and J. Morris, supported by NIH Grants: NIH P30 AG066444, P50 AG00561, P30 NS09857781, P01 AG026276, P01 AG003991, R01 AG043434, UL1 TR000448, and R01 EB009352).

Amyloid-clearing drug fails to change waste clearance function in the brains of Alzheimer's patients

 

Whoops, lecanemab is not for me. With my damaged brain already running with millions to billions less neurons I'll pass on more brain shrinkage. But I'm not medically trained so don't listen to me.

From this article comes the following paragraphs:

YIKES! FDA Approves Lecanemab Against Alzheimer’s

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.” 

Amyloid-clearing drug fails to change waste clearance function in the brains of Alzheimer's patients

A group from Osaka Metropolitan University in Japan, led by graduate student Tatsushi Oura and Dr. Hiroyuki Tatekawa, found that treatment using the drug lecanemab to remove amyloid plaques in the brain does not change the waste clearance function in the brains of Alzheimer's disease (AD) patients in the short term.

This suggests that even after treatment, the AD patients' nerves are already damaged, and the waste clearance function does not recover in the short term. Their findings show the complexity of the disease and the need to address multiple disease-causing pathways simultaneously in the future.

Their findings add to the complicated process of unraveling AD's mechanisms. Despite being the most common form of neurodegenerative disease, it is tricky to treat because of its multiple causes.

One cause of the nervous damage common in AD is the accumulation of the protein amyloid-β (Aβ) in the brain. In healthy patients, the glymphatic system moves cerebrospinal fluid along the spaces around the arteries into the brain tissue, where it mixes with interstitial fluid to carry away metabolic waste like Aβ. This is called the 'glymphatic system' after the glial cells involved in the process.

However, in AD patients, Aβ builds up, stiffening arteries and reducing the flow from the brain to the cerebrospinal fluid. This blockage triggers a chain of neurodegenerative processes, leading to AD symptoms.

The recently approved therapeutic lecanemab reduces accumulated Aβ. The team from the university's Graduate School of Medicine evaluated the glymphatic system before and after treatment in patients who received lecanemab therapy, using the DTI-ALPS index.

Contrary to expectations, they found no significant change in the index between pre-treatment and 3 months after treatment.

They concluded that although anti-amyloid therapy can reduce plaque burden and slow further cognitive worsening, it may be insufficient to restore lost function. This suggests that neuronal damage and clearance system deficits have already been well established by the time the patient starts showing symptoms. Their findings show the range of factors involved in the progression of AD, many of which are not easily reversible.

Even when Aβ is reduced by lecanemab, impairment of the glymphatic system may not recover within the short-term. In the future, we want to look at factors like age, the stage of the disease, and degree of lesions in the white matter to further understand the relationship between changes in the glymphatic system due to lecanemab treatment and the outcome of treatment. This will help understand the best way to administer treatment to patients."

Tatsushi Oura, graduate student, Osaka Metropolitan University

The study was published in Journal of Magnetic Resonance Imaging.

Source:

Osaka Metropolitan University

Journal reference:

Oura, T., et al. (2025). Unchanged Early Diffusion Tensor Imaging Along Perivascular Space Index After Amyloid‐Targeting Disease‐Modifying Therapy in Alzheimer’s Disease: A Preliminary Study. Journal of Magnetic Resonance Imaging. doi: 10.1002/jmri.70118. https://onlinelibrary.wiley.com/doi/10.1002/jmri.70118

Turn Back Your Brain’s Bioenergetic Clock to Reduce Alzheimer’s Risk

 Whoops, lecanemab is not for me. With my damaged brain already running with millions to billions less neurons I'll pass on more brain shrinkage. But I'm not medically trained so don't listen to me.

From this article comes the following paragraphs:

YIKES! FDA Approves Lecanemab Against Alzheimer’s

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.” 

Now if we could just get our stroke medical 'professionals' to do their jobs on this research and create EXACT PROTOCOLS on this, that would be excellent. But that won't occur; I've never seen any sign of excellence in stroke in the 15 years I've been writing this blog. Excellence is getting survivors to 100% recovery; NOT the tyranny of low expectations your stroke medical 'professionals' try to foist off on you since they incompetently haven't done a damn thing to get survivors to 100% recovery.

Turn Back Your Brain’s Bioenergetic Clock to Reduce Alzheimer’s Risk

Summary: Researchers have discovered that a person’s “bioenergetic age,” reflecting how efficiently cells produce energy, strongly predicts Alzheimer’s risk and progression. High blood levels of molecules called acylcarnitines, markers of aging metabolism, were linked to faster cognitive decline and greater Alzheimer’s symptoms.

However, lifestyle choices like plant-based diets and regular exercise can effectively lower these molecules, reducing bioenergetic age and potentially delaying Alzheimer’s onset. This bioenergetic approach could help identify individuals at risk earlier and provide personalized strategies to maintain brain health without relying solely on medication.

Key Facts:

• Bioenergetic Clock: High acylcarnitine levels indicate an older bioenergetic age, significantly linked to Alzheimer’s risk.
• Lifestyle Benefits: Healthy living, including diet and exercise, can lower bioenergetic age, potentially offering protective benefits similar to Alzheimer’s medications.
• Personalized Prevention: About 30% of study participants with genetic risks but favorable bioenergetic profiles may especially benefit from lifestyle interventions.

Source: Weill Cornell University

A person’s “bioenergetic age”—or how youthfully their cells generate energy—might be a key indicator of whether they’re at risk of developing Alzheimer’s disease, new research from Weill Cornell Medicine shows.

The study, published Feb. 24 in Nature Communications, suggests healthy living can turn back the bioenergetic clock for some people, helping them fend off Alzheimer’s as effectively as a new drug called lecanemab.

The benefit is on par with the Alzheimer’s drug lecanemab. Credit: Neuroscience News

“That’s quite big because it means some people can lower their risk without the uncertain side effects of current treatments,” said senior author Dr. Jan Krumsiek, associate professor of physiology and biophysics and computational genomics in the Institute for Computational Biomedicine at Weill Cornell Medicine. The study’s first author, Dr. Matthias Arnold, is head of the computational neurobiology team at Helmholtz Munich.

The new findings bring us a step closer to solving a long-standing puzzle. One of the early warning signs of Alzheimer’s is that brain cells start losing their ability to produce and use energy efficiently, such as metabolizing glucose (sugar). But some people don’t show disease symptoms for years.

This delay between abnormalities in energy pathways and the onset of symptomatic disease suggests there is a “bioenergetic capacity” that provides a buffer for these individuals. Their bodies and brains are better at keeping energy levels up even when problems start.

“In these cases, people can be unusually healthy when we look at their cognition,” said Dr. Krumsiek, who is also a member of the Englander Institute for Precision Medicine. “They make it to old age without the kind of declines that usually creep in.” 

But could the researchers identify individuals with this beneficial higher bioenergetic capacity and help those without it?

A New Tool to Predict Risk of Alzheimer’s

Dr. Krumsiek and his colleagues turned to a group of molecules called acylcarnitines, which are associated with declining cognition and breaking down or metabolizing fats and proteins for energy.

To test if high acylcarnitine levels in the blood could predict who’s at risk of developing Alzheimer’s, the researchers used data from a large-scale study called the Alzheimer’s Disease Neuroimaging Initiative.

“It was fascinating,” Dr. Krumsiek said.

“Dividing research participants into groups based on their specific acylcarnitine levels highlighted people with more severe Alzheimer’s disease and others with fewer symptoms.”

This led the researchers to define a bioenergetic clock based on acylcarnitines—how old a person’s metabolism acts, compared to actual age. Higher bioenergetic age is linked to higher acylcarnitine levels, worsened Alzheimer’s pathology, cognitive decline and brain atrophy.

The researchers also quantified cognitive decline using a common test called the mini-mental state examination, on which a score below 24 out of 30 points indicates impairment.

They found that people with low acylcarnitine levels to begin with declined more slowly, losing about 0.5 points less per year than people with high acylcarnitine levels. The benefit is on par with the Alzheimer’s drug lecanemab.

To some degree, a person’s bioenergetic clock ticks forward at a rate determined by their genetics, but having a healthy lifestyle—for example, eating a plant-based diet and exercising —can help keep acylcarnitine levels low, which means a younger bioenergetic age, Dr. Krumsiek explained.

They went on to identify a subgroup of participants, about 30% of the Alzheimer’s Disease Neuroimaging Initiative, with older bioenergetic age but favorable genetic background.

These individuals may benefit more from early lifestyle interventions designed to decrease their bioenergetic age and potentially delay or prevent the onset of Alzheimer’s.

Next Steps

Moving forward, Dr. Krumsiek hopes to home in on the lifestyle interventions most effective for lowering bioenergetic age. For example, eating a low-carb diet may help maintain metabolic health, but just how low would carbohydrate consumption have to be for a person to see benefits?

The study also points to an inexpensive, rapid test that could determine a person’s acylcarnitine levels.

“It’s fortunate that these blood tests—originally developed to identify metabolic and mitochondrial disorders in newborns—can also help assess a person’s bioenergetic age,” Dr. Krumsiek said.

“If we can repurpose this technology for older adults, that could provide a way to start personalized treatment earlier.”

About this bioenergetic age and Alzheimer’s disease research news

Author: Barbara Prempeh
Source: Weill Cornell University
Contact: Barbara Prempeh – Weill Cornell University
Image: The image is credited to Neuroscience News

European committee says Alzheimer’s treatment Leqembi shouldn’t get marketing approval

 And this article doesn't even mention brain shrinkage.

Whoops, not for me. With my damaged brain already running with millions to billions less neurons I'll pass on more brain shrinkage. But I'm not medically trained so don't listen to me.

From this article comes the following paragraphs:

YIKES! FDA Approves Lecanemab Against Alzheimer’s

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 latest here:

European committee says Alzheimer’s treatment Leqembi shouldn’t get marketing approval

Shares of Biogen slid Friday after a European regulatory committee said the Alzheimer’s treatment Leqembi should not receive marketing approval.

The European Medicines Agency committee said concerns about the drug’s potential side effects outweigh the impact it has in slowing the fatal, mind-robbing disease.

Japanese drugmaker Eisai developed Leqembi and is co-marketing it with Cambridge, Massachusetts-based Biogen Inc. An Eisai executive said in a statement that company officials were “extremely disappointed,” and they will ask for a re-examination of the decision.

The European Committee for Medicinal Products for Human Use recommended 14 new medicines for approval at its July meeting. Leqembi was the only one to receive a negative opinion.

The treatment already has received approval in the United States, Japan, China, South Korea, Hong Kong and Israel.

Leqembi clears a sticky brain plaque linked to the disease. A large study has shown that it slowed memory and thinking decline by several months in those who received the treatment compared to those who got a dummy drug.

But it also can cause brain swelling and bleeding, side effects that can be dangerous in rare cases.

TD Cowen analyst Phil Nadeau said in a note that he was surprised and disappointed by the committee decision. But he said it does not affect his sales estimates because he assumed any European launch “would be very slow as reimbursement was negotiated and the complicated logistics of diagnosis and treatment were worked out.”

Leqembi received full approval last year from the U.S. Food and Drug Administration. Earlier this month, the FDA also approved another drug that takes a similar approach, Eli Lilly’s Kisunla.

Biogen’s stock fell more than 4% to $216.82 after markets opened Friday, and Lilly shares slipped 1%. The Standard & Poor’s 500 index climbed nearly 1% at the start of trading.

It's the First Drug Shown to Slow Alzheimer's. Why Is It Off to a Slow Start?

 Whoops, not for me. With my damaged brain already running with millions to billions less neurons I'll pass on more brain shrinkage. But I'm not medically trained so don't listen to me.

From this article comes the following paragraphs:

YIKES! FDA Approves Lecanemab Against Alzheimer’s

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 latest here:

It's the First Drug Shown to Slow Alzheimer's. Why Is It Off to a Slow Start?

The first drug shown to slow Alzheimer's disease hit the U.S. market over a year ago, but sales have lagged, major hospital systems have taken months to start using it, and some insurers have rejected coverage.

Doctors also expect some patients will hesitate to take lecanemab (Leqembi) due to its limited impact and potential side effects. They say it will take years to learn how best to deploy the drug and that work must be done to improve diagnosis.

"This is the start of a very exciting journey," said Ambar Kulshreshtha, MD, a suburban Atlanta family physician focused on dementia patients.

More than 6 million Americans, and millions more worldwide, have Alzheimer's disease, the most common cause of dementia. There's no cure, but lecanemab clears a sticky brain protein called amyloid that's a key indicator of Alzheimer's.

Studies showed that it can delay the progression of the disease by a few months when given to people with mild symptoms. Some experts say the delay may be too subtle for patients to notice.

The drug also can cause brain swelling and bleeding. Patients need regular brain scans to monitor for that.

The FDA gave lecanemab full approval last summer for patients with early stages of the disease. The federal Medicare program for people ages 65 and over covers lecanemab and the cost of scans needed to diagnose patients.

The drug's maker, Japan's Eisai, initially expected to have 10,000 patients taking the IV drug by the end of March. Company executives have since backed off that projection, though they say sales are growing.

Hospitals and health systems have needed more time than expected to set up their systems for delivering lecanemab, said Alexander Scott, an Eisai executive vice president.

"It's not like we are adding a drug to an existing system," he said. "They are building the system for the drug."

The Cedars-Sinai health system in Los Angeles started administering the drug in early March. Getting there required months of meetings to iron out a plan to coordinate diagnosis, treatment, and then monitoring for problems.

"We were very careful about it," said Sarah Kremen, MD, a behavioral neurologist.

Banner Health in Arizona also recently started using lecanemab at a couple specialty clinics in Phoenix, a spokeswoman said.

"This is a very phased and staged approach," said Alireza Atri, MD, PhD, a neurologist who has worked as a paid consultant for Eisai. "As we learn more, we'll expand and extend it."

The Mayo Clinic in Rochester, Minnesota, started using lecanemab in October but only for patients who live within a 100-mile radius so it can reach them quickly if they develop side effect symptoms. Doctors evaluate three to five patients every week for potential treatment, said Alzheimer's expert Ron Petersen, MD, PhD.

Health systems are still trying to understand how coverage for the drug, its infusions, and the needed scans works so patients don't get stuck with bills. That's a significant variable for a drug that can cost more than $26,000 a year.

An Eisai spokeswoman said nearly three-quarters of commercial plans in the U.S. cover the drug outside Medicare.

But doctors are concerned that coverage still may be tough for some patients, especially those too young to qualify for Medicare.

Insurance denials delayed Scott Berkheiser's first lecanemab infusion a few months until last December. The 57-year-old Venice, Florida, resident said the drugmaker eventually agreed to give it to him for free while he makes co-payments for the infusions.

"It was a little crazy," he said. "It seemed like it was kind of a game that must make sense for some monetary reason."

Getting treatments started on time remains another challenge.

Texas Neurology had 60 patients screened as possible candidates for lecanemab and on a waitlist when the drug launched last year. Only eight eventually started treatment. The rest either declined to take it or had advanced beyond the mild phase of the disease when they were rescreened, CEO David Evans said.

"That window gets very short very quick," he said.

Doctors say more must be done to quickly identify patients and get treatment started before the disease advances. But that's a murky process.

If people mention memory trouble, doctors must rule out reversible causes like thyroid problems, vitamin deficiencies, medication issues, or depression, Kulshreshtha said. Then memory tests for dementia can take a few visits.

Some patients may be ineligible for lecanemab because it would conflict with medication they already take to prevent strokes.(Ask your competent? doctor what those medications are.)

And then getting in to see a neurologist who prescribes the drug can take months.

Those who make it to the first infusion say the treatment process is manageable. Berkheiser says infusions have gone "like clockwork" since his delayed start.

He fits them in between his work as an engineer and training 6 days a week to compete in an Ironman triathlon.

Charles "Bum" Clegg recently finished his 13th lecanemab infusion. The Salem, Alabama, resident visits a treatment center only 15 minutes from his home.

Clegg and his wife, Carol, say he has had no side effects, and his short-term memory has improved.

"This drug gives you hope," Carol said.

Treatment access may improve over time. The FDA is reviewing another potential treatment that targets amyloid protein, Eli Lilly's donanemab. Eisai is planning to seek approval for an injectable version of lecanemab that would be easier to use. Blood tests may eventually speed up amyloid detection.

But researchers say there's still a long road ahead. It's not clear what causes Alzheimer's disease, and many think combination treatments will be needed to stop it.

"We still have a lot to learn about Alzheimer's," said Eric Widera, MD, a geriatric specialist with the University of California San Francisco. "It's complex, and it's much more than amyloid."

FDA Panel Backs Traditional Approval of Lecanemab for Alzheimer Disease

 

Whoops, not for me. With my damaged brain already running with millions to billions less neurons I'll pass on more brain shrinkage. But I'm not medically trained so don't listen to me.

From this article comes the following paragraphs:

YIKES! FDA Approves Lecanemab Against Alzheimer’s

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 latest here:

FDA Panel Backs Traditional Approval of Lecanemab for Alzheimer Disease

Although lecanemab may have adverse events, such as infusion reactions, amyloid related imaging abnormalities-hemosiderin deposition, and superficial siderosis, it can help in the treatment of AD as an IgG1 monoclonal antibody.

The Food and Drug Administration’s (FDA) Peripheral and Central Nervous System Drugs Advisory Committee (PCNS) voted unanimously (6 “yes” to 0 “no”) that lecanemab-irmb (Leqembi^®) shows clinical benefit as a treatment for Alzheimer disease (AD).

Lecanemab is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta. In January 2023, the FDA granted accelerated approval to lecanemab for the treatment of AD based on data from a phase 2b trial (ClinicalTrials.gov Identifier: NCT01767311). In March 2023, lecanemab received Priority Review for its supplemental Biologics License Application seeking to convert its accelerated approval status to a traditional full approval.

The panel reviewed efficacy and safety data from the confirmatory phase 3 Clarity AD trial (ClinicalTrials.gov Identifier: NCT03887455), which included 1,795 patients with early AD. Patients were randomly assigned 1:1 to receive either lecanemab 10 mg/kg via intravenous infusion once every 2 weeks or placebo. The primary endpoint was the change from baseline to 18 months in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score.

Results showed a statistically significant treatment difference in the CDR-SB score change (-0.45; P =.00005), indicating a reduction in clinical decline of 27% with lecanemab over 18 months compared with placebo. Findings also showed statistically significant improvements in all key secondary endpoints compared with placebo (P <.001), including changes in amyloid levels in the brain (as measured by amyloid positron emission tomography), the AD Assessment Scale-Cognitive Subscale 14 (-1.44 [95% CI, -2.27, -0.61]), the AD Composite Score (-0.050 [95% CI, -0.074, -0.027), and the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (2.0 [95% CI, 1.2-2.8]).

The most common adverse events reported with lecanemab were infusion reactions (26.4% vs 7.4% with placebo), amyloid related imaging abnormalities-hemosiderin deposition (ARIA-H; combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis: 17.3% vs 9.0% with placebo), ARIA-E (edema/effusion: 12.6% vs 1.7% with placebo), headache (11.1% vs 8.1% with placebo), and fall (10.4% vs 9.6% with placebo).

Alzheimer's Drug Wins Full FDA Approval

Whoops, not for me. With my damaged brain already running with millions to billions less neurons I'll pass on more brain shrinkage. But I'm not medically trained so don't listen to me.

From this article comes the following paragraphs:

YIKES! FDA Approves Lecanemab Against Alzheimer’s

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 latest here:

Alzheimer's Drug Wins Full FDA Approval

Decision expands lecanemab's Medicare coverage

by Judy George, Deputy Managing Editor, MedPage Today July 6, 2023

Lecanemab (Leqembi) became the first Alzheimer's treatment targeted at the disease process to win full FDA approval, the agency announced today.

"Today's action is the first verification that a drug targeting the underlying disease process of Alzheimer's disease has shown clinical benefit in this devastating disease," said Teresa Buracchio, MD, acting director of the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research. "This confirmatory study verified that it is a safe and effective treatment for patients with Alzheimer's disease."

Full FDA approval expands the drug's Medicare coverageo, giving more Alzheimer's patients access to the drug.

Reaching this milestone in Alzheimer's disease treatment has been "a long journey," said Babak Tousi, MD, of the Cleveland Clinic in Ohio, an investigator in the lecanemab clinical trials. "We can affect the disease trajectory -- it's a small benefit, but it's still a benefit. We can slow it down."

"This was a big step for us, and it's not just because of the effect of the disease treatment," Tousi noted. "We learned more about the disease and learned how to diagnose it more accurately, and how to look at the process of the disease progression and biomarkers."

In January, lecanemab was approved under the accelerated approval pathway to treat Alzheimer's disease. As part of the accelerated approval, drugmakers Eisai and Biogen were required to conduct a postmarketing trial verifying lecanemab's clinical benefit.

The confirmatory study, the phase III CLARITY AD trial, showed lecanemab led to less decline on cognitive and functional measures in early Alzheimer's disease, but was associated with adverse events.

The primary efficacy endpoint was change on the Clinical Dementia Rating-Sum of Boxes (CDR-SB), a scale that ranges from 0-18, with higher scores indicating worse impairment. From a baseline score of about 3.2 on the CDR-SB, mean worsening at 18 months was 1.21 with lecanemab and 1.66 with placebo, a difference of 0.45 points. All key secondary endpoints were met.

Adverse events included amyloid-related imaging abnormalities (ARIA) with edema or effusions (ARIA-E), which occurred in 13% of people who received lecanemab. ARIA with hemosiderin deposition (ARIA-H), which includes cerebral hemorrhage and superficial siderosis, occurred in 17%.

Three subgroups appeared to have a higher risk of adverse events: APOE4 homozygotes, people with underlying cerebral amyloid angiopathy, and people who require concomitant treatment with anticoagulant agents.

A boxed warning is included in the lecanemab prescribing information to alert patients and caregivers to the potential risks associated with ARIA, the FDA said. The prescribing information states that testing for APOE4 status should be performed before starting treatment to inform patients of ARIA risk, and recommends caution for patients taking anticoagulants or those who have other risk factors for intracerebral hemorrhage.

Several reports indicated that three people died during the lecanemab open-label extension study, though it was unclear what role the drug may have played. Recent research also suggested that anti-amyloid therapies for Alzheimer's disease, including lecanemab, may accelerate brain atrophy.

Last month, an FDA advisory committee unanimously agreed that lecanemab showed clinical benefit in early Alzheimer's disease in its confirmatory trial. In a 6-0 vote, the agency's Peripheral and Central Nervous System Drugs Advisory Committee fully backed the evidence supporting the anti-amyloid monoclonal antibody.

The CLARITY AD findings were "robust on the primary and all the key secondary" outcomes, said FDA advisory committee member Merit Cudkowicz, MD, of Harvard Medical School and Massachusetts General Hospital in Boston. "I was also impressed that the effect was seen relatively early -- in 6 months -- and then it seemed to get bigger with time."

YIKES! FDA Approves Lecanemab Against Alzheimer’s

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

The FDA granted accelerated approval to lecanemab for Alzheimer's. What's the back story? New reports of brain shrinkage are worrisome to us.

YIKES! FDA Approves Lecanemab Against Alzheimer’s

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Alzheimer’s Disease

Joe Graedon

April 18, 2023

29 Comments

FDA Approved words on an orange pill or medicine bottle with long shadow

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.