Results from trials of lecanemab, a drug that targets amyloid buildup in the brain, are a step forward, but it’s not clear whether this treatment will actually help people affected by Alzheimer’s disease.
September 28, 2022
The results of the trial of a new drug to treat Alzheimer’s disease have been described as a historical breakthrough and in unequivocal victory for those with the condition. Its developer, the Japanese firm Eisai, has even said the results “prove” the hypothesis that the disease is caused by a buildup of a protein called amyloid in the brain.
The results are certainly promising, not to mention surprising, but it is an exaggeration to present them as an unequivocal victory for patients, and the amyloid hypothesis has yet to be definitively proven.
For decades, it has been widely held that Alzheimer’s disease is caused by amyloid buildup that contributes to brain cell death, leading to memory loss and confusion. Unfortunately, many drugs that were designed to remove amyloid have not shown a benefit in trials.
The new drug, called lecanemab, is an antibody that binds to amyloid, causing the immune system to remove it from the brain. The latest study compared lecanemab infusions given once every two weeks with placebo treatment in nearly 1,800 people. with Alzheimer’s disease in a randomized, 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, the symptom scores of those who received the real treatment had decreased 27 percent less than those of the placebo group, according to a Summary of results published online today.
This may sound impressive, but the difference in 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 significant difference in people’s lives, any treatment would need to improve scores by a little more than that, between 0.5 and 1.0 points, he says. Robert Howard at University College London, which was not involved in the study.
It is possible that if people were given the treatment for longer, the effect size would increase, but this is not certain. It’s also possible that lecanemab’s side effects caused some people to assume they had received the real drug, which would have potentiated any placebo effects seen by them or their caregivers, Howard says.
If so, the drug would appear more effective than it really is. We can’t know if 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 percent of those who received lecanemab and 9 percent of those who received the placebo.
This level was “within expectations,” says Eisai. But in practice, this could mean that people taking the treatment would need regular brain scans to check for safety.
Eisai says it plans to apply for regulatory approval for lecanemab in the US, Europe and Japan in March of next year. In the UK, there would be an additional hurdle: treatment would only be offered through health services if its benefits are calculated to outweigh its costs. This is by no means certain what could be a difference in symptoms so small that those affected and their families would not even notice it.
Tellingly, 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 was highly controversial as trials did not show that it caused any improvement in symptoms, just that it helped clear amyloid.
Aducanumab causes brain swelling and bleeding in 4 out of 10 recipients. The latest results from lecanemab suggest that these symptoms could be a typical effect of anti-amyloid drugs.
Despite all these caveats, the latest results, if confirmed, would be a step forward for Alzheimer’s research, as lecanemab is the first disease-modifying Alzheimer’s treatment to have a positive effect on symptoms, even if it’s a very small one. It may be that, in the future, a better balance between desired effects and side effects can be achieved by lowering the dose, using the drug in combination with another drug, or adjusting the mechanism, says Howard.
So the results could reasonably be seen as good news for those researching Alzheimer’s disease, but not so much for current sufferers.
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