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‘Momentous breakthrough’: New Alzheimer’s drug lives up to bold claims, with caveats

The new drug isn't a cure, but it extends the functional life of a damaged brain.

The new drug isn't a cure, but it extends the functional life of a damaged brain. Photo: Getty

Last month, a drug company put out a press release claiming that an experimental drug had, for the first time, “unambiguously” slowed  cognitive decline and brain damage in Alzheimer’s patients.

The drug ‘lecanemab’ – developed by Tokyo pharmaceutical company Eisai, and biotechnology firm Biogen in Cambridge, Massachusetts – is a monoclonal antibody that was said to remove clumps of amyloid proteins that are thought to kill brain cells and result in memory loss.

Esteemed neuroscientists, long desperate for good news, fell over themselves to declare this an “historic” moment – while at the same time crossing their fingers and cautioning that the claims needed to be supported by full data from a Phase III clinical trial.

Bingo!

That data was published this week in the New England Journal of Medicine, supporting the claims that lecanemab had reduced cognitive and functional decline by 27 per cent in the trial.

In effect, the drug makers are enjoying a second round of ecstatic headlines – with many news outlets also pretending the news is brand new.

Fair enough. It’s a very big deal.

However, this time round there has been a more immediate focus on side effects, including bleeding on the brain in nearly one-in-five trial participants.

The trial

The Phase III trial involved 1795 volunteers, aged 50 to 90, in the early stages of Alzheimer’s disease.

Half of the participants were given an infusion of lecanemab every two weeks. The other half received a placebo.

The memory and cognitive function of all participants was regularly tested over 18 months.

At the start of the trial, participants from both groups had a ‘clinical dementia rating’ or CDR-SB score of about 3.2 – a score consistent with early Alzheimer’s disease.

Higher scores indicate greater cognitive decline.

By the end of the trial, the CDR-SB score in the lecanemab group was up 1.21 points. In the placebo group, it was up 1.66.

Measuring amyloid beta proteins

Lecanemab works by binding to amyloid beta proteins, considered a diagnostic characteristic of Alzheimer’s.

At the study’s starting point, the average amyloid level in the lecanemab group was 77.92 centiloids. In the placebo group it was lower, 75.03 centiloids.

An Alzheimer’s brain showing amyloid protein clumps (the dark circles).

After 18 months, the average amyloid level dropped 55.48 centiloids in the lecanemab group. In the placebo group it had increased by 3.64 centiloids.

As the authors of the new paper concluded: “Lecanemab reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months, but was associated with adverse events.

“Longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease.”

For an explainer on what the results mean – and an explainer as to why amyloid beta is a complicated measuring tool – see here.

Side effects

During the trial, as reported by Nature, about 20 per cent (one in five) of participants who received lecanemab showed abnormalities on their brain scans that indicated swelling or a small amount of bleeding, “although less than 3 per cent of those in the treatment group experienced symptoms of these side effects”.

However, 9 per cent of those in the placebo group also suffered these side effects.

If the drug is given regulatory approval, and the developers are hoping to see this fast-tracked in the US, Europe and Japan by March in 2023, regular safety scans may be deemed necessary.

Some awkward history

Biogen, the Massachusetts-based developer, in June last year gained controversial approval from the FDA for the drug aducanumab, another monoclonal antibody designed to treat Alzheimer’s – but there was no proven clinical benefit.

As I reported at the time, in one of two clinical trials, the drug, aducanumab, was found to slow the rate of cognitive decline by about 25 per cent in patients with mild cognitive impairment (MCI), a precursor to dementia, or very early Alzheimer’s dementia.

Professor Chris Rowe – a nuclear medicine physician and neurologist – told me that the treatment should have been restricted to these patients.

But in the US, aducanumab was made available to anyone who could afford it.

Professor Rowe said MCI means “you have memory problems, and don’t do too well on testing, but you’re coping with life pretty well”.

He said that the drug – developed over a fraught decade – might give patients with severe dementia a couple of extra months of living. But they would still be unable to feed or wash themselves, the damage to their minds profound and irreversible.

Aducanumab would be of no use to them.

The new drug, lecanemab, is certainly a big step up.

In the next year or so, we will hopefully see new and improved drugs that build on this breakthrough.

A reality check

While a reduced cognitive and functional decline of 27 per cent sounds impressive, the actual clinical improvement is modest. For someone with Alzheimer’s, though, it’s a big something – where for decades there has been no real improvement.

For Alzheimer’s patients and their families, it is a matter of managing expectations.

Last month, Professor Tara Spires-Jones, Group Leader at the UK Dementia Research Institute at the University of Edinburgh, said: “While this is not a ‘cure’ in that it doesn’t bring people back to normal, slowing cognitive decline and preserving the ability to perform normal daily activities would still be a huge win because people could live well for longer with Alzheimer’s disease.”

And that’s worth shouting about more than once.

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