By Charlotte Webster-
Doctors have hailed a “new era” of medicine after a study showed for the first time that a drug can slow the debilitating symptoms of Alzheime
Millions of people suffer from Alzheimer’s, which sees proteins build up and form abnormal structures in the brain, killing nerve cells and brain tissue progressively.
Researchers have been developing a promising drug called lecanemab, and the results of its phase 3 trial show the drug reduces the amount of protein buildup in the brain, which could effectively slow down the onset of dementia.
Results from the clinical trial also revealed that the drug lecanemab cleared clumps of a protein called amyloid – thought to be a key cause of the most common form of dementia – from patients’ brains.
The data, published at a conference in San Francisco, has led to optimism from scientists, many of whom had spent decades trying to understand what leads to the disease and find a treatment.
There is debate among scientists and doctors about the “real world” impact of lecanemab.
The slower decline with the drug was noticed using ratings of a person’s symptoms. It’s an 18-point scale, ranging from normal through to severe dementia. Those getting the drug were 0.45 points better off.
Prof Spires-Jones said that was a “small effect” on the disease, but “even though it is not dramatic, I would take it”.
Dr Susan Kohlhaas, from Alzheimer’s Research UK, said it was a “modest effect… but it gives us a little bit of a foothold” and the next generation of drugs would be better.
There are also risks. Brain scans showed a risk of brain bleeds (17% of participants) and brain swelling (13%). Overall, 7% of people given the drug had to stop because of side effects.
A crucial question is what happens after the 18 months of the trial, and the answers are still speculation.
Dr Elizabeth Coulthard, who treats patients at North Bristol NHS Trust, says that people have, on average, six years of living independently once mild cognitive impairment starts.
Slow that decline by a quarter and it could equate to an extra 19 months of independent life, “but we don’t know that yet”, she says.
It is even scientifically plausible that the effectiveness could be greater in longer trials. “I don’t think we can assume that this is it,” says Dr Kohlhass.
The emergence of drugs that do alter the course of the disease asks big questions of whether the health service is ready to use them.
The drugs have to be given early in the disease before too much damage to the brain is done, whereas most people referred to memory services are in the later stages of the disease.
That requires people coming forward at the earliest signs of memory problems and doctors being able to send them for amyloid tests – either brain scans or spinal fluid analysis – to a determine if they have Alzheimer’s or another form of dementia. At the moment only 1-2% of people with dementia have such tests.
The Alzheimer’s Society says more than 850,000 people in the UK have some form of dementia. More than half have Alzheimer’s, but everyone would need testing.
“There’s an enormous gulf between current service provision and what we need to do, to deliver disease modifying therapies,” said Dr Coulthard.
She said that, currently, only those living near big medical centres or paying privately were likely to benefit.
Scientists also stressed that amyloid was only one part of the complex picture of Alzheimer’s disease and should not become the sole focus of therapies.
Immune System
The immune system and inflammation are heavily involved in the disease and another toxic protein called tau is the one that’s found where brain cells are actually dying, Prof Spires-Jones.
She added: “I’m very excited we’re on the cusp of understanding enough to get a hold of the problem and we should have something that will make a bigger difference in a decade or so.”
Results were “wonderful and hope-filled” – adding: “At long last we have gained some traction on this most terrible and feared disease and the years of research and investment have finally paid off.
“It feels momentous and historic. This will encourage real optimism that dementia can be beaten and one day even cured.”
The manufacturers of the drug released top-line results in a news release earlier in the autumn, but many doctors held back from celebrating until full results were released at the Clinical Trials on Alzheimer’s Disease conference.
They showed that lecanemab slowed the decline in memory and mental agility by 27% in patients with mild Alzheimer’s.
Critically, the drug removed so much of the amyloid protein that the patients wouldn’t have had enough evidence of Alzheimer’s disease on their brain scans to actually qualify for entry to the trial.
The study strongly suggests that the drug only starts to have a clinical effect once amyloid is reduced to low levels in the brain.
Results after 12 months of treatment suggested it was ineffective – but after 18 months, the effect was significant.
Doctors are optimistic that continued treatment will lead to even better results.
Professor Nick Fox, director of the Dementia Research Centre at University College London, said: “It confirms a new era of disease modification for Alzheimer’s disease, an era that comes after more than 20 years of hard work by many, many people, with many disappointments along the way.”
Lecanemab is not a cure. But even slowing the progression of Alzheimer’s disease would be game changing, delaying the need for specialist care and allowing people to spend more time with their families.
Side Effects
One in eight patients suffered brain swelling and other changes, probably as a result of removing the amyloid protein. But most only had evidence of problems on brain scans. Fewer than one in 30 had actual symptoms such as headaches or confusion.
Some patients had bleeding in the brain, though deaths were no higher in those receiving treatment than those given a dummy drug.
Nevertheless, it underlines the need for careful monitoring of those on treatment.
Prof Fox said: “Any risk is clearly important, but I believe that many of my patients would be very willing to take such a risk.
Doctors warned that lecanemab will be a massive challenge for the NHS, not just because the drug is given through an intravenous infusion every two weeks.
Most Alzheimer’s patients are currently diagnosed when they have moderate symptoms – too late for treatment with lecanemab. And just 1% have their diagnosis confirmed by a brain scan or lumbar puncture, a biopsy of their spinal fluid.
Susan Kohlhaas, director of research at Alzheimer’s Research UK said: “It’s safe to say that the NHS is not ready for a new era of dementia treatment.
“We estimate that unless there are drastic changes in how people access specialist diagnostic tests for Alzheimer’s disease, only 2% of people eligible for drugs like lecanemab will be able to access them.”
Until now there have only been drugs that treated symptoms rather than the underlying cause. But if lecanemab is licensed for use on the NHS then delays in treatment will result in brain cells dying and the disease progressing.
Prof John Hardy, from the UK Dementia Research Institute in London said the drug had been “a long time coming”.
He added: “I truly believe it represents the beginning of the end.
“The first step is the hardest, and we now know exactly what we need to do to develop effective drugs. It’s exciting to think that future work will build on this, and we will soon have life-changing treatments to tackle this disease.”