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Alzheimer’s drug Leqembi backed by FDA expert panel for full approval

Breakthrough Alzheimer’s drug Leqembi has received the unanimous support of a US Food and Drug Administration advisory panel – all but ensuring full approval for the first of its class treatment.
The FDA’s Peripheral and Central Nervous System Drugs Advisory Committee (PCNS) voted 6-0 that data showed Leqembi – also known as lecanemab – demonstrated a clinical benefit to patients.
The PCNS came to its decision after reviewing evidence from a Phase 3 Clarity AD clinical trial that showed Leqembi slowed cognitive and functional decline in patients by 27% compared to a placebo at 18 months.
The FDA will decide on July 6 whether to endorse the drug made by Japanese pharmaceutical company Eisai and Massachusetts-based global biotechnology firm Biogen.
Leqembi received accelerated approval from the FDA for the treatment of early Alzheimer’s disease on January 6, 2023 and was launched in the US on January 18 this year.
The accelerated approval which allows for faster consent for drugs for serious conditions that fill an unmet medical need, was based on Phase 2b data that demonstrated that Leqembi reduced the accumulation of amyloid-beta plaque in the brain, a neuropathological hallmark of Alzheimer’s disease.
But this approval restricted Leqembi, which is administered twice a month intravenously, to patients who could either pay $26,500 a year or, in the case of the US Government’s Medicare national health insurance programme for seniors and the disabled, to those who were enrolled on a clinical trial. This even though there are no clinical trials underway.
However, FDA approval would mean that Leqembi would become more readily available through Medicare with the agencies running the programme, The Centers for Medicare and Medicaid Services (CMS), having promised to broadly cover the cost of the drug for patients who are willing to take part in a national data registry to track “evidence about how these drugs work in the real world.
But that listing has yet to be created and the US-based Alzheimer’s Association has described making registry a condition of coverage an “unnecessary and potentially harmful barrier.”
Joanne Pike, the Alzheimer’s Association’s president and CEO, said: “We are in full agreement with the FDA Advisory Committee that Leqembi provides clinical benefit and that this benefit outweighs the risks.
“Now all eyes turn to CMS. Medicare is supposed to be a rock-solid guarantee for Americans, and it is time for CMS to step up and provide Medicare access on the day of an FDA traditional approval.

Alzheimer’s drug Leqembi. Image: Eisai Co.
“Americans living with Alzheimer’s disease deserve access to FDA-approved therapies without barriers, just like people with cancer, heart disease and HIV/AIDS.”
According to the Alzheimer’s Association, 6.5 million Americans are currently living with the disease, which robs patients of their memory and causes other cognitive problems.
The organisation says Alzheimer’s and other dementias will cost the US $345bn this year. That cost is predicted to rise to $11bn annually by 2050 as more people are diagnosed with the condition.
Leqembi, which is an anti-amyloid treatment, changes the course of Alzheimer’s and has been shown to deliver clear clinical benefit for people in the early stages of the disease.
By slowing progression in the early stages of Alzheimer’s, the treatment will give people more time to participate fully in daily life, help make important decisions, and live independently.
This could mean more time for a person to take care of family finances, and engage in hobbies and interests.
Phase 3 data from the Clarity AD global clinical trial published in the New England Journal of Medicine showed Leqembi met both the primary and all key secondary endpoints for the patient population with highly statistically significant results.
As with other anti-amyloid treatments in this class of drugs, Leqembi does have side effects, including brain swelling and bleeding.
Three deaths from brain haemorrhages occurred in the extended part of the trial. The FDA said the patients had a disorder called cerebral amyloid angiopathy, which is the build up of amyloid in small arteries and capillaries in the brain, a condition that can be difficult to detect by imaging tests.
Despite this, Dr Pike has welcomed the FDA Advisory Committee’s decision. She said: “The Alzheimer’s Association welcomes and celebrates this action by the FDA Advisory Committee to support traditional approval of Leqembi for people with early Alzheimer’s.
“With this action we are one step closer to more people living with Alzheimer’s having more time with more of their capabilities intact – to do the things they want to do and love to do best.”
Myra Garcia, a member of the Alzheimer’s Association Early Stage Advisory Group, spoke to the committee hearing and said: “While the thought of a cure for Alzheimer’s disease is certainly part of my optimism, I’d like you to know that for me, more time is enough for now. And that is the promise of treatments like lecanemab.”
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Study shows clear link between CTE and dementia risk

A new study says CTE should be recognised as a cause of dementia, with those in the most advanced stages facing a 4.5-fold higher lifetime risk.
Chronic traumatic encephalopathy (CTE) is a degenerative brain condition seen in some athletes.
Linked to repeated head impacts, it can cause memory loss, mood changes, poor coordination and suicidal thoughts. Diagnosis is only possible after death.
People with the most advanced CTE were 4.5 times more likely to develop dementia during life than people without CTE, researchers found.
Many former NHL and NFL players have been posthumously diagnosed with CTE, including Junior Seau, Frank Gifford and Ken Stabler.
The study from researchers at the Boston University CTE Center provides what the centre describes as the clearest evidence yet linking CTE to dementia risk.
The centre says these findings indicate CTE should be known as a cause of dementia.
“This study provides evidence of a robust association between CTE and dementia as well as cognitive symptoms, supporting our suspicions of CTE being a possible cause of dementia,” said Dr Michael Alosco, an associate professor of neurology and co-director of clinical research at the BU CTE Center.
“Establishing that cognitive symptoms and dementia are outcomes of CTE moves us closer to being able to accurately detect and diagnose CTE during life, which is urgently needed.”
Researchers studied brain tissue from more than 600 donors, the majority men.
The donors, primarily contact sport athletes, had known exposure to repetitive head impacts, but none had Alzheimer’s disease, Lewy body disease or frontotemporal lobar degeneration.
They found that 366 male donors had CTE. After examining the donor brains, they calculated the odds of developing dementia across CTE stages I to IV.
Donors with stages III and IV had the worst cognitive and functional symptoms, regardless of age or history of substance use treatment.
Lower stages were not associated with dementia, cognitive impairment or functional decline.
The team also found no link between less severe CTE and changes in mood or thinking, suggesting observed changes may stem from other effects of repetitive head impacts or unrelated medical or environmental factors.
“Understanding which brain changes drive cognitive decline is essential,” said Dr Richard Hodes, director of the National Institute of Health’s National Institute on Aging.
“This study shows that only severe CTE has a clear link to dementia, which provides an important distinction for researchers, healthcare providers and families.”
The study also found that dementia due to CTE is often misdiagnosed as Alzheimer’s disease.
Both conditions are marked by abnormal tau proteins that build up in brain cells and affect blood vessels, although the tau differs in each disease.
Of donors with CTE who had received a dementia diagnosis during life, 40 per cent were told they had Alzheimer’s disease but showed no evidence of it at autopsy.
A further 38 per cent of families were told the cause of dementia was unknown or could not be specified.
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ATW’s research round-up: new Alzheimer trigger identified, UK university targets longevity. fibre not protein?…and more

A UK university will become one of the first in the country to make improving the health and well-being of the elderly one of its six ‘mission-led’ research priorities.
Bournemouth University’s choice to focus on pensioners is partly the result of the Labour Government’s wish for universities to specialise, whilst also reflecting the area’s demographics – the south-coast city has one of the one of the oldest populations in the world.
“Our demographics are much older than other places – about 10 years older on average compared to the rest of the UK,” explained Tom Wainwright, professor of orthopaedics at Bournemouth.
Vary your exercise
The university’s Orthopaedic Research Institute is already heavily involved in work with the surrounding area and its recently published study, in The Lancet, showed that over-65s with osteoarthritis who undertook group-based cycle classes enjoyed much better outcomes than those receiving one-to-one physiotherapy.
Research published in leading British doctors’ publication the BMJ Journal, which tracked 100,000 people over the last 30 years, has shown that mixed exercise routines can have a significant impact on overall health and longevity.
The study tracked the cohorts exercise habits over three decades and found that participants who engaged in the highest variety of exercises had a 19% lower risk of death, compared to those who engaged in the lowest variety.
Benefits were even bigger when looking at specific causes like heart disease, cancer, and respiratory illness, with risk reductions ranging from 13 to 41 percent.
“People naturally choose different activities over time based on their preferences and health conditions,” says Yang Hu, corresponding author and research scientist in the Harvard TH Chan Department of Nutrition.
“When deciding how to exercise, keep in mind that there may be extra health benefits to engaging in multiple types of physical activity, rather than relying on a single type alone.”
US researchers have identified over five dozen new potential blood-based metabolites which could predict a Type 2 diabetes risk, years in advance.
Key Alzheimer trigger identified
Scientists at Mass General Brigham and Albert Einstein College of Medicine, followed 23,634 participants for up to 26 years and over that time analysed 469 metabolites in blood samples, alongside additional genetic, diet and lifestyle data.
In doing so they identified 235 metabolites associated with higher or lower diabetes risk, including 67 new molecules previously unreported.
The researchers say their work supports a shift toward precision prevention strategies which are more reliable than current indicators such as BMI or family history.
Further research into the Alzheimer’s predicting APOE (apolipoprotein E) gene has left UK researchers with renewed conviction of their ability to develop preventive measures, earlier in life.
Researchers at University College London analysed nearly 470,000 people across four major studies, focusing on participants aged 60 and older with confirmed Alzheimer’s diagnoses and genetic data.
Whilst previous studies had identified the ε4 allele of APOE as the one most predictive of Alzheimer’s development the UCL researchers also highlighted how allele ε3 may also carry a significant risk
Dr Dylan Williams, the study’s lead author, explained that the APOE gene’s contribution to the prevalence of Alzheimer’s has been significantly underestimated for a long time, and that the ε3 allele has historically been misunderstood as having a neutral effect on risk.
He said: “Intervening on the APOE gene, or the molecular pathway between the gene and Alzheimer’s, could have huge potential for preventing or treating a large majority of cases.”
Fibre first
Researchers say that fibre – found in beans, lentils, chia seeds, oats, bran, and certain fruits – is emerging as the ‘new hero’ of nutrition science.
Longevity expert Dr Vassily Eliopoulos, MD, who trained at Cornell, highlights how protein has ruled diet trends for years, but says fibre is now stepping into the spotlight.
“Everyone’s chasing protein, but the next big longevity macro is fibre. And fibre might be the most under-appreciated longevity nutrient that you’re missing daily.”
Explaining why fibre plays such a crucial role, he highlights the connection between gut health and overall well-being.
“Here’s the secret, your gut microbes eat what you don’t digest. These microbes convert fibre into powerful compounds that protect the body. They turn fibre into short-chain fatty acids, which act as your body’s natural anti-inflammatory molecules,”
Dr Eliopoulos highlights how chronic inflammation is closely linked to ageing and disease and he recommends aiming for 30 to 40 grams of fibre a day.
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