Breakthrough dementia drugs — what went wrong and what happens next?

On September 29, 2022, experts hailed “a historic moment for dementia research” when the world welcomed a long-awaited drug breakthrough. A trial had definitively proven for the first time that a medicine both cleared toxic amyloid protein from the brains of Alzheimer’s patients and significantly delayed progression of symptoms. It felt like a watershed moment in the battle against one of the most feared diseases of old age. However, today — 1,290 days later — almost no UK patients are able to access the treatment.

So what went wrong and what could happen next? The Express has taken a look at the latest dementia drug developments. The trial results that sent ripples of excitement through research circles were for lecanemab, a drug developed by Tokyo-based Eisai and US firm Biogen. The data showed it slowed cognitive decline by 27% over 18 months, described as a “modest but clear” benefit.

One expert declared: « God knows, we’ve waited long enough for this. » Another said that while the drug was not a cure, it heralded “a transformation in outlook for people with the first signs of Alzheimer’s disease”.

But in the months that followed, a debate emerged about just how modest these results were. What does a 27% slowing actually mean for your loved one who is in the early stages of Alzheimer’s?

Some experts began to argue that the drug’s benefits were too small to be noticeable in a real-world setting, outside of a clinical trial where the most subtle changes can be measured.

Meanwhile, there were rare but serious side effects — the rate of brain swelling was 12.5% for patients on the medication, versus 1.7% in the placebo group.

Similar results were unveiled the following year for a second drug, donanemab.

A briefing paper published by NHS England in 2024 showed that the number of patients eligible for disease modifying treatment was estimated to be between 50,000 and 280,000.

Charities called for the health service to prepare for a rollout by boosting diagnosis rates and ensuring more people can access the tests needed to confirm a specific diagnosis.

The Medicines and Healthcare products Regulatory Agency gave the green light to lecanemab in August 2024, deciding it was safe and effective for use in the UK.

But the hopes of thousands of potential patients were immediately dashed when, in a rare coordinated move, the National Institute of Health and Care Excellence (NICE) announced simultaneously that it would not be recommending the drug for use on the NHS.

It said the medication slowed progression of the disease by between four and six months, a benefit ruled “too small to justify the cost”.

NHS drug pricing negotiations are confidential but at the time lecanemab was thought to cost around £20,000 per patient per year in the US. The cost of regular scans and appointments to monitor patients was estimated at a further £19,000.

Dementia charities and campaigners were disappointed. David Thomas, Alzheimer’s Research UK’s head of policy, predicted the ruling would put the drug out of reach for “all but the most wealthy”.

The same ruling — licensed, but not approved for the NHS — followed for donanemab in October 2024.

Today, the small number of UK patients who are accessing the drugs are either paying privately or enrolled in a clinical trial. No reliable data exists on the number but it is thought to fall in the low hundreds.

The Express revealed last month that patients are also travelling from abroad to access private prescriptions in London. Lykke Vestergaard Kastbjerg, 42, who makes the journey from Denmark every month with her father Niels, 73, said: “It’s my dad’s life, it doesn’t have a price for me.”

It would be easy to rage at the injustice of this situation. When a drug exists that can slow a disease as devastating as Alzheimer’s, why can the NHS and government not find a way to provide access, even to a limited group?

However, we must remember that every drug funding decision has consequences. I attended a medical conference in Berlin many years ago where there was a thought-provoking talk on treatment access campaigns.

Heartbreaking appeals from patients desperate to try the latest life-changing therapy can be extremely powerful and compelling, the speaker said. But funding a drug for one person might effectively mean taking a treatment away from someone else. The NHS has a finite pot of cash, which is why NICE must be the arbitrator of cost effectiveness.

Many experts who were bitterly disappointed at the rejection of the two dementia drugs would also acknowledge that these were probably the right decisions.

NICE announced last month that it would review elements of its assessments following appeals from the manufacturers. It admitted, for example, that it did not fully take into account the impact of dementia on unpaid carers.

But this review is not expected to overturn the overall ruling on either treatment. NICE has said the drugs were estimated to cost five to six times more than the threshold it would normally recommend. New thresholds now apply which are even higher.

For the drugs to be approved, one side of the equation would need to shift dramatically; the proven benefit must be greater or the price lower.

Nonetheless, there is hope on the horizon. New trials are investigating whether combining one of these drugs with those targeting other brain pathologies, such as Lewy bodies or tau tangles, produces a better result.

And a second generation of anti-Alzheimer’s drugs is already in development. One example is remternetug, considered the follow up to donanemab and made by the same manufacturer, Eli Lilly.

It is being tested in a phase three trial with more than 1,600 patients aged 60-85, which is expected to complete this year. It can be given via a subcutaneous injection similar to an insulin pen, rather than the intravenous method used in earlier trials, which could bring down administration costs.

A major independent review by the London-based global organisation Cochrane is expected to publish its assessment of the anti-amyloid drugs landscape next week.

Cochrane Reviews, which analyse all the high-quality evidence on a topic, are internationally recognised as the gold standard of evidence-based medicine. They can be highly influential and NICE committees often use these rigorous reports to make clinical recommendations.

Other drugs in development are not targeting amyloid at all, instead focusing on other toxic proteins associated with Alzheimer’s such as tau.

Charities have rightly continued to call for the NHS and ministers to prepare to roll out disease-modifying treatments. Around one million people are living with dementia in the UK but one in three have no diagnosis, creating an immediate barrier.

Professor Fiona Carragher, Alzheimer’s Society’s chief policy and research officer, has warned that “the science is flying but the system is failing”.

She said last summer: “Even if donanemab and lecanemab were made available on the NHS tomorrow, too many patients wouldn’t be able to access them because the health system isn’t ready to deliver them. »

Lecanemab and donanemab may not be the first therapies rolled out on the NHS, but they were breakthrough drugs — the first to move beyond just masking symptoms to actually tackle the underlying disease pathology.

Being a step closer to a widely available NHS treatment may still seem like a step too far away for the thousands of families affected by dementia in the UK.

However, a first-in-class medicine is rarely the best and there is a strong global pipeline of drugs in development. An annual report by renowned US neurologist Dr Jeffrey Cummings found there were 138 Alzheimer’s drugs being assessed in 182 clinical trials in January 2025, up from 127 drugs in 164 trials the previous year.

It may take a little longer than first hoped when that breakthrough was celebrated in 2022, but there is no doubt that we are moving in the right direction.