We have proven that a drug can slow Alzheimer's. Now it should be cheaper

On Thursday morning, almost two years after those results were published, the Medicines and Healthcare products Regulatory Agency (MHRA) announced that lecanemab was “safe and effective” for certain groups, making it the first drug that slows the underlying cause of Alzheimer's to receive a drug approval in the UK.

But the moment was bittersweet, as the National Institute for Health and Care Excellence (Nice) announced at the same time that the benefits were “too small to justify the significant cost to the NHS”: more than £30,000 per patient per year, including staff and scans. This decision, which is expected to save around £2 billion a year, denies the drug to around 70,000 patients in England who would otherwise have been eligible.

Private clinics, however, are not restricted by Nice and will offer the drug. One of these clinics, Re:Cognition Health, says treatments will begin at its London and Bristol sites in October, with four more sites to follow. The Cleveland Clinic in London is currently considering whether to offer the drug.

Private fortnightly treatments are likely to cost at least £50,000 a year, so only the wealthy are likely to be able to afford them.

“There will be a flood of GoFundMe campaigns,” says Hardy. With the European Medicines Agency rejecting the drug last month, British clinics are likely to face increased interest from the continent as well.

But what does this mean for the remaining 600,000 people in the UK who suffer from Alzheimer's, the most common form of dementia? Will scientists have to start all over again?

First flight

Hardy acknowledges that lecanemab, made by pharmaceutical giants Eisai and Biogen, is not perfect. He believes the same is true of the next iteration, donanemab, made by rival Eli Lilly. That drug is awaiting a decision from UK regulators in the next few months and is also expected to be rejected. The effect of both is modest: a 27 percent reduction in cognitive decline with lecanemab corresponds to a mere five-month break; donanemab has a similar effect. Some patients suffer serious consequences, including brain haemorrhages.

“But these drugs clearly work and they point the way to developing better drugs in the future,” says Hardy.

He compares these first-generation treatments to the Wright brothers' first flight in 1903. “Many people said they would never fly. But on that beach in North Carolina they showed that it was possible with what was basically a modified bicycle. Within a few years there were flights across the English Channel. Once you know you can do something, it's much easier to do it better.”

Richard Oakley, deputy director of research at the Alzheimer's Society, puts it differently: “Too often we throw the baby out with the bathwater and give up on goals because the first or second drug doesn't work. Chemotherapy was brutal in the early days – the doses were too high and we gave them for too long. But we haven't given up on it; we've made improvements.”

Combating brain hemorrhages

A major problem with lecanemab and the other anti-amyloid drugs is inflammation of the brain, which occurs in 13 to 45 percent of patients taking these drugs, depending on genetic predisposition. In some patients it causes headaches, in others it leads to brain bleeding. A few have died from it.

Robert Howard, professor of geriatric psychiatry at University College London, who has long been a critic of these drugs, says: “Inflammation is the body's response to a foreign body in the brain. I don't think you can get better results with an antibody against amyloid without getting even worse side effects. I think they have reached the limits of what these drugs can do.”

Hardy disagrees, pointing out that the inflammatory effect occurs in the blood vessels before the drug crosses the “blood-brain barrier,” a membrane that protects neurons but that drugs have difficulty penetrating. One estimate is that out of 3,000 molecules of an anti-amyloid drug administered, only one reaches the brain cells.

The Swiss pharmaceutical company Roche has found a possible solution: a technique it calls “Brain Shuttle.” It uses a “Trojan horse” to transport drugs across the blood-brain barrier. Roche's new drug Trontinemab uses this technology to transport amyloid-eliminating antibodies into brain cells.

“That's the secret sauce,” says Hardy. “You can use much lower concentrations of the antibody, which obviously means you need less of it, and it gets to the brain faster, so it clears the disease more effectively.” If there's less drug in the blood vessels, there should be less inflammation.

New hopes

But amyloid is not the only possibility. Hilary Evans-Newton, chief executive of Alzheimer's Research UK, says: “There are currently over 160 trials worldwide involving over 125 experimental treatments for Alzheimer's, including 30 in advanced trials.”

Of these, only 20 use the amyloid approach. The others target other mechanisms. “It's really just a question of when, not if, new treatments will become available,” she says.

Researchers are also excited about treatments that target another protein called tau, which accumulates in tangles in the brain. One such drug, a pill called hydromethylthionine mesylate (HMTM), is already under review by the MHRA.

Scientists are also studying gene editing, anti-inflammatory treatments and the way cells communicate. Of great interest are stem cell therapies that can stop and even reverse brain damage.

Perhaps the most radical new approach is to try to simply turn off Alzheimer's. The emerging field of gene silencing allows doctors to administer treatments that “turn down” the production of harmful proteins. Initial treatments have been tested on both tau and amyloid.

Hardy says: “If someone had suggested this to me ten years ago in a grant application, I would have said it would never work. But the first results are really convincing. That really gives hope.”

Neglected dementia

The most common form of dementia is Alzheimer's, which affects around 600,000 of the one million dementia patients in the UK, but there are many other forms.

Oakley says we should take a step back and pay more attention to these other diseases. “There are forms of dementia where amyloid and tau are not the triggers: frontotemporal dementia, vascular dementia, dementia with Lewy body syndrome,” he says. “I wonder where the studies are on these diseases? We're not even getting there yet.”

When it comes to Alzheimer's, however, Oakley is confident that an effective drug will soon be available for patients. “Alzheimer's was discovered in 1906, and now, in 2024, we have nothing for most patients. But they don't have to wait long – we're on the right track.”