‘Best ever’ Alzheimer’s drug can halt disease

Breakthrough delays mental decline by third and may stop symptoms worsening for a year

THE drug hailed as the best ever for Alzheimer’s disease has been found to slow decline by a third, in a breakthrough that ushers in a new era of treatment for dementia.

Eli Lilly, the US pharmaceutical company, announced yesterday that its drug donanemab delayed the worsening of symptoms by 35 per cent, a result described as “remarkable” by experts.

In half of patients, the drug halted mental decline for more than a year.

British scientists hailed the trial results as “hugely exciting” and the Alzheimer’s Society said it signalled “the beginning of the end of Alzheimer’s”.

“This result confirms we are now entering the treatment era of Alzheimer’s disease,” said Dr Cath Mummery, a consultant neurologist at University College London Hospitals NHS Foundation Trust.

“We are now entering the time of disease modification, where we might realistically hope to treat and maintain someone with Alzheimer’s disease, with long-term disease management, rather than palliative and supportive care.”

Existing drugs boost chemical signals in the brain, or treat symptoms such as insomnia or depression, but cannot stop progression.

However, use on the NHS is probably a long way off as the new treatment, given once a month by infusion, would need to be approved by the Medicines Healthcare and Products Regulatory Agency (MHRA), and the National Institute for Health and Care Excellence (Nice), a process which can take years.

The number of people living with dementia, mainly Alzheimer’s, is expected to increase to more than one million by 2030.

The condition costs the country £34.7billion annually and is now the leading cause of death.

Donanemab is the second Alzheimer’s drug to prove successful in the past year after Eisai/biogen’s lecanemab was shown to slow decline by 27 per cent.

Donanemab works by clearing the brain of sticky amyloid plaques that stop brain cells communicating.in recent years, scientists have doubted whether removing amyloid was the correct strategy, after the failure of several trials of drugs to break up the plaques.

However, John Hardy, professor of Neuroscience at University College London (UCL), said the trial results should “dispel any lingering doubts” that the way to treat Alzheimer’s was to remove amyloid from the brain.

The study involved 1,182 patients with early Alzheimer’s.

As well as postponing a worsening of symptoms, the drug allowed patients to continue to perform daily activities for longer. The study also enrolled 552 people who were at a later stage, and results showed it slowed down disease progression by up to 29 per cent.

Eli Lilly said it would apply to the US Food and Drug Administration (FDA) for approval this quarter, and “proceed with global regulatory submissions as quickly as possible”.

British experts called on regulators to quickly license the therapies here. Lecanemab received FDA approval in January, but has yet to be granted MHRA approval.

Dr Richard Oakley, associate director of research at Alzheimer’s Society, said: “We need decisions as quickly as possi- ble from MHRA and Nice.

“But that’s not the end of the story – we can’t end up in a situation where there are new drugs being approved but people can’t get access to them early in their dementia journey when they work best – we need more accurate, earlier dementia diagnosis in the NHS.”

Dr Tom Russ, director of the Alzheimer Scotland Dementia Research Centre at the University of Edinburgh, added: “The NHS is not ready to implement an infusion-based therapy such as donanemab or lecanemab should they become licensed treatments in the UK.

“There needs to be significant support for struggling dementia assessment services which are still emerging from the Covid-19 pandemic to continue to diagnose, treat, and support people currently presenting.”

It has taken decades of research and billions of pounds, but suddenly the dark veil of Alzheimer’s appears to be lifting. In the past nine months, two drugs which slow down the progress of the disease have succeeded in clinical trials, the first time anything has offered a lifeline for people drowning under a diagnosis of dementia.

Where once scientists were ultracautious about giving false hope, now there is genuine optimism in the field. Expert reactions yesterday to trial results were infused with words like “remarkable”, “exciting” “impressive” and “breakthrough”.

The Alzheimer’s Society, known for its measured response to clinical findings, even enthused: “This could be the beginning of the end of Alzheimer’s disease.”

In the same way that cancer is no longer considered a death sentence,

Alzheimer’s looks set to become a treatable disease, rather than a punishing and irrevocable stripping of self ahead of a premature death.

But while the results are promising there are still reasons to be cautious. Scientists are still waiting to see the full-trial data, which has not yet been published or peer-reviewed. There also appear to be significant and worrying side-effects linked to the new drug. In the latest Eli Lilly trial, around one quarter of the 1,182 patients experienced brain swelling or microbleeds. Three died.

It will be up to regulators such as the Medicines Healthcare and Regulatory Agency to decide whether such risks outweigh the benefits. There may also be longer-term effects that won’t become apparent for several years.

And these drugs are likely to be very – possibly prohibitively – expensive, requiring monthly infusions and regular brain scans to monitor amyloid levels as well as to check for brain swelling and bleeds. NHS dementia assessment services are already struggling amid a growing number of diagnoses and many believe the Health Service is simply not ready to implement such advanced treatments.

What is hopeful, however, is that we finally seem to know at least the cause of dementia and how to set about tackling it. The “amyloid hypothesis” was suggested decades ago, after brain scans showed the sticky plaques increased as cognition declined. Yet trials of drugs to get rid of amyloid continually failed until recently.

The new trial proves scientists were right all along. Dramatic and rapid amyloid removal in the brain was accompanied by slowing of cognitive decline. Now we have a good target, we should be able to build increasingly effective, cheaper and safer weapons.

Undoubtedly we are standing on the cusp of a first generation of treatments for Alzheimer’s disease, a situation that many thought impossible even just 10 years ago. Perhaps one day we will be celebrating a drug that does not just slow down Alzheimer’s but stops it altogether. Now that will be a day to remember.

Undoubtedly we are standing on the cusp of a first generation of treatments for the illness