Could the tide finally be turning in the hunt for an effective treatment for Alzheimer’s disease? That was the suggestion from a story last week about a new drug, lecanemab, which seems to improve symptoms of early Alzheimer’s.
For decades, scientists have been working on drugs to treat the condition without much success, so understandably there was excitement after the pharmaceutical companies behind lecanemab — Eisai and Biogen — announced that it slowed early Alzheimer’s, specifically cognitive decline, by 27 per cent over 18 months in a trial of 1,795 people.
However, while this was greeted as an ‘historic moment’, the trial data is not yet available for independent scrutiny — and previous experience with similar medicines suggests we should be cautious.
The preliminary lecanemab data is unique as it shows the drug can slow down disease progression
Last year, Good Health reported on aducanumab, the first new medicine for Alzheimer’s in two decades to be approved by the U.S. regulator, the Food and Drug Administration (FDA).
The approval was controversial because despite clearing plaque in the brain (seen as a hallmark of Alzheimer’s), the drug did not significantly improve symptoms.
In addition, more than 35 per cent of the trial participants experienced brain side-effects, including swelling, reported a study in the journal JAMA Neurology earlier this year, which analysed data from a number of trials.
There are also ongoing investigations into a very small number of patients who died after taking aducanumab. Lecanemab works in a similar way to aducanumab (but seems to target a slightly different type of amyloid) — and the preliminary data suggests the rate of side-effects, such as brain swelling or bleeding, was 21.3 per cent in the lecanemab group and 9.3 per cent in the placebo group; something the developers described as ‘within expectations’.
Both aducanumab and lecanemab clear the brain of plaque, formed of a build-up of a sticky protein called amyloid — this has been linked to dying nerve cells.
Until now, most drugs that target the amyloid, including aducanumab, haven’t led to a clinical benefit, i.e. improved brain function or memory.
The preliminary lecanemab data is unique as it shows the drug can slow down disease progression.
However, some experts have said the drug’s ability to slow cognitive decline is modest and it is not yet clear whether patients will find it meaningful.
The approval was controversial because despite clearing plaque in the brain (seen as a hallmark of Alzheimer’s), the drug did not significantly improve symptoms
In the trial, the difference between people who received the drug and those who had a placebo amounted to 0.45 points on the 18-point clinical dementia rating scale, which measures memory and cognitive ability.
As one expert commented: ‘The accepted minimum worthwhile difference ranges from 0.5 to 1.0 point.’
There are other challenges, such as convenience — it’s given as a fortnightly infusion; although a simpler injection of lecanemab is also being tested in early-stage trials.
The developers say the trial results will be presented at a conference on November 29 and published in a peer-reviewed journal, with plans to file for approval in the U.S., Japan and Europe by next March.
However, like aducanumab, lecanemab has been given fast-track status by the FDA which could see it approved in the U.S. in January.
Clearly there is huge interest in a cure for dementia — but what’s not clear is if we’re a step closer to that holy grail.
What the experts say
Professor Tara Spires-Jones, group leader at the UK Dementia Research Institute at Edinburgh University, said: ‘If the data hold up to scrutiny, this is indeed fantastic news. 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 daily activities would still be a huge win.’
Dr Charles Marshall, an honorary consultant neurologist at Queen Mary University of London: ‘The benefits are fairly small and will need to be balanced against the risks of side-effects including inflammation and bleeding in the brain.’
Peter Passmore, a professor of ageing and geriatric medicine at Queen’s University Belfast:‘[clinIcal benefits] seem to be small and the debate will be around how clinically relevant the changes are.’
Masud Husain, a professor of neurology at Oxford University: ‘While the summary of the results seems very encouraging, we have to be cautious until we are allowed to review the data fully. It is also important to bear in mind that the trial results apply only to people with mild Alzheimer’s disease . . . and that there were important side-effects.’
Rob Howard, a professor of old age psychiatry at University College London:
‘This is an unambiguously statistically positive result and represents something of an historic moment.’