Alzheimer’s drug results are promising – but not a major breakthrough

Trial results for lecanemab, a drug that targets amyloid build-up in the brain, are a step forward, but it is unclear if this treatment will truly help those affected by Alzheimer’s disease

By Clare Wilson

Lecanemab targets amyloid build-up in the brain

Science Photo Library / Alamy

Trial results for a new medicine to treat Alzheimer’s disease have been described as a historic breakthrough and an unequivocal win for those with the condition. Its developer, Japanese firm Eisai, has even said the results “prove” the hypothesis that the disease is caused by a build-up of a protein called amyloid in the brain.

The results certainly are promising, not to mention surprising, but it is stretching things to paint them as an unequivocal win for patients, and the amyloid hypothesis hasn’t yet been definitely proven.

For decades, it has been widely held that Alzheimer’s disease is caused by amyloid build-up contributing to the death of brain cells, leading to memory loss and confusion. Unfortunately, many drugs that were designed to remove amyloid haven’t shown a benefit in trials.

The new drug, called lecanemab, is an antibody that binds to amyloid, leading to it being cleared from the brain by the immune system. The latest study compared infusions of lecanemab given once every two weeks with a placebo treatment in nearly 1800 people with early Alzheimer’s disease, in a randomised and blinded trial.

People were assessed for the severity of their symptoms using a battery of memory and other cognitive tests, as well as interviews with their caregivers and doctors. After 18 months, symptom scores for those given the real treatment had declined 27 per cent less than those in the placebo group, according to a summary of the results posted online today.

This may sound impressive, but the difference in the scores between the two groups was small, a matter of 0.45 points on an 18-point scale. Previously, some researchers in this area have estimated that to make a meaningful difference to people’s lives, any treatment would need to improve the score by a little more than that – by 0.5 to 1.0 points, says Robert Howard at University College London, who wasn’t involved in the study.

It is possible that if people received the treatment for longer, the size of the effect would increase – but this isn’t certain. It is also possible that side effects from lecanemab led some people to guess they had received the real drug, which would have enhanced any placebo effect seen by them or their caregivers, says Howard.

If so, the drug would seem more effective than it really is. We can’t know whether this happened until the results are published in full in a peer-reviewed journal.

Another problem is that the drug caused the potentially serious side effects of brain swelling and small bleeds in the brain, seen on brain scans. These occurred in 21 per cent of those given lecanemab and 9 per cent of those given the placebo.

This level was “within expectations”, says Eisai. But in practice, this could mean that people taking the treatment would need periodic brain scans to check on safety.

Eisai says it plans to apply for regulatory approval for lecanemab in the US, Europe and Japan by March next year. In the UK, there would be a further hurdle: the treatment would only be offered through health services if its benefits are calculated to outweigh its costs. This is by no means certain for what could be a difference in symptoms so small that those affected and their families wouldn’t even notice it.

Tellingly, the side effects of brain swelling and bleeding have also been seen with another amyloid-targeting Alzheimer’s drug called aducanumab. This was approved for use in the US last year, but it was highly controversial, as trials had failed to show it caused an improvement in symptoms, merely that it helped clear amyloid.

Aducanumab causes brain swelling and bleeding in 4 out of 10 recipients. The latest results for lecanemab suggest that these symptoms could be a typical effect of amyloid-targeting drugs.

Despite all these caveats, the latest results – if they are borne out – would indeed be a step forward for Alzheimer’s research, as lecanemab is the first-ever disease-modifying Alzheimer’s treatment that has a positive effect on symptoms, even if it is a very small one. It may be that, in future, a better balance of desired effects and side effects is achieved by reducing the dosage, using the drug in combination with another medicine or tweaking the mechanism, says Howard.

The results could therefore reasonably be seen as good news for those who research Alzheimer’s disease – but not so much for those who are affected by it today.