It was hailed as the "beginning of the end" for Alzheimer's disease back in November 2022.

The results of a Phase Three clinical trial published in the prestigious New England Journal of Medicine declared that the drug lecanemab, manufactured by Tokyo-based Eisai, had slowed disease progression by 27% over 18 months when compared to patients on a placebo.

It was the first time that any medicine had been shown to clear amyloid clumps from the brains of Alzheimer’s patients, and appeared to back up the long-running theory that build ups of these sticky protein clusters cause the disease to advance.

It was a historic breakthrough, coming exactly 30 years after the amyloid theory had first been outlined in 1992.

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Excitement over lecanemab was followed in 2023 by news of even better results for a similar drug - Eli Lilly's donanemab - after its Phase Three clinical trial found that it slowed cognitive decline by 35% on average among people in the early stages of Alzheimer's.

Initially, the main obstacle seemed to be the practicalities of rolling out these drugs on the NHS.

Alzheimer's is the leading - but not the only - cause of dementia.

Crucially, other forms of dementia, such as vascular or Lewy-Body, are not associated with amyloid build ups.

Given that lecanemab and donanemab are only effective as treatments for Alzheimer's, and even then only in the earliest stages, it was suddenly crucial to ensure that patients could be identified quickly and accurately.

The NHS had a mountain to climb.

Fewer than 1% of patients currently seen by UK dementia clinics have a precise diagnosis of Alzheimer’s disease.

Until now, there was no incentive to distinguish the Alzheimer's from non-Alzheimer's patients because there was no treatment that could help.

Achieving diagnosis is also complicated.

Currently, it can only be detected by screening spinal fluid extracted during a lumbar puncture, or via a PET scan of the brain.

Currently, accurate diagnosis of Alzheimer's requires invasive lumbar punctures of the spine or PET scans of the brain - but the NHS has far fewer PET machines per head of population than similar European countriesCurrently, accurate diagnosis of Alzheimer's requires invasive lumbar punctures of the spine or PET scans of the brain - but the NHS has far fewer PET machines per head of population than similar European countries (Image: Getty)

Then there was the problem of finding cases early enough, given that the earliest symptoms of Alzheimer's disease (losing things, forgetting names, trouble following a conversation) are unlikely to trigger people to seek a GP appointment.

Most people experience symptoms for around three and a half years before being diagnosed - generically - with "dementia".

Even if all this could be turned around, there was still the difficulty of supplying enough manpower to ensure that all eligible patients could receive their fortnightly intravenous doses of lecanemab, and be monitored for side effects.

For now, these dilemmas are on the backburner. This "game-changing" drug has been rejected for use on the NHS.

On August 22, UK regulator the Medicines and Healthcare products Regulatory Agency (MHRA) announced that it was approving lecanemab for use in the "early stages of Alzheimer’s disease" - but only in certain patients.

One of the key complications associated with the medicine is that some patients develop Amyloid Related Imaging Abnormalities (ARIAs).

Patients receiving lecanemab would have to be monitored for signs of bleeding and swelling in the brain - one of the more dangerous potential side effectsPatients receiving lecanemab would have to be monitored for signs of bleeding and swelling in the brain - one of the more dangerous potential side effects (Image: Getty)

Usually, these are temporary swellings or small spots of bleeding in or on the surface of the brain.

In most cases, these ARIA events are only found by an MRI brain scan and do not cause any symptoms.

However, there were three deaths attributed to lecanemab during the clinical trial and its extension phase.

This would be yet another hurdle for the NHS, as patients receiving lecanemab would have to undergo regular brain scans.

Analysis shows that the risk of developing symptomatic, serious and recurrent ARIA events while receiving the drug varies depending on patients own DNA.

Those with two copies of a gene called apolipoprotein E4 (ApoE4) - around 15% of Alzheimer's patients - had a 45% risk compared to 19% for patients with only one copy, and 13% among those who do not carry it at all.

As a result, the MHRA approved lecanemab only for those with "one or no copies" of the gene variant; among those with two copies, the potential risk outweighed the potential benefit.

That is the function of the regulator: to evaluate the safety of medicines.

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By contrast, NICE - the body which decides which drugs should be made available on the NHS in England and Wales - has to weigh up cost-effectiveness.

Its equivalent in Scotland, the Scottish Medicines Consortium (SMC) has yet to rule on lecanemab, but it is probable it will reach the same conclusion.

On the same day that the MHRA issued its verdict, NICE concluded that the benefits "are too small to justify the costs".

An estimated 70,000 adults in England would have been eligible.

Based on US prices, lecanemab costs around £20,000 per patient per year, but exactly what it would have cost the NHS is unclear (compared to insurance-based systems, drug companies typically negotiate a confidential, lower price with the NHS because it is in their interests to access such a large patient population).

Whatever was offered, however, NICE said that the "relatively small benefits" for patients - delaying the worsening of symptoms such as memory loss by four to six months - "cannot be considered good value for the taxpayer".

It was estimated that 70,000 people in England would have been eligible, had NICE recommended lecanemab for the NHSIt was estimated that 70,000 people in England would have been eligible, had NICE recommended lecanemab for the NHS (Image: Getty Images)

Where we go from here depends on a number of things.

One hope is that new blood tests, currently in the pipeline, will make detecting Alzheimer's much easier.

Increased competition (dozens of similar drugs are still in trials) could also drive down prices.

Most importantly, the benefits have to get much bigger to make the cost worthwhile.

A drug capable of slowing Alzheimer's onset by years - or, the ultimate holy grail, stopping it altogether - could pay for itself in social care savings.

Within the scientific community, opinions are mixed.

Some argue that real-world benefits are probably even slimmer and the risks higher, with severe and sometimes fatal ARIAS perhaps affecting as many as one in 50 patients.

Others remain convinced that the amyloid hypothesis is a dead end; that drugs like lecanemab might slow dementia initially, but do nothing in the medium to late stages of the disease.

The optimistic take is that the next generation of medicines will deliver greater benefits with less risk, and the NHS must get ready for them now.

After all the hype, the outlook is uncertain.