Experimental Alzheimer’s drug shows promise, but there are still many hurdles to overcome

The first drug that can slow the decline in Alzheimer’s patients has been found. The experimental drug, called lecanemab, is an antibody that targets the toxic clumps of amyloid protein associated with the brain-ravaging disease. While these results are cause for celebration, there are still important questions about its security and rollout.

The full results of the phase 3 trial of lecanemab drugs (the final phase of human testing) have been published in the New England Journal of Medicine. The trial showed that after 18 months of treatment, patients who received the drug had a 27% slower rate of disease progression than those who received a placebo.

In general, this is good news. For the first time, we have a potential treatment that has a demonstrated effect on both the symptoms and the underlying pathology of Alzheimer’s disease. These results are a breakthrough in the search for treatments for this devastating disease and strongly indicate that the course of the disease can be changed.

But the results paint a mixed picture for people with Alzheimer’s disease. On the one hand, this is the first drug that has been shown to have any effect on slowing the progression of the disease. On the other hand, the apparent effects are minor and the risks are not inconsiderable.

About 1,800 people with early-stage Alzheimer’s participated in the global trial. The participants were randomly assigned to receive intravenous lecanemab or placebo every two weeks. The study was “double-blind,” meaning that neither the participants nor the researchers knew who received the experimental drug and who received the placebo until the end of the trial.

Throughout the study, participants’ disease progression was monitored using the Dementia Clinical Rating Scale, which scores the patient on cognition and ability to live independently. Participants’ brains were also scanned for the two proteins commonly associated with Alzheimer’s disease: amyloid and tau.

Alzheimer’s scores in both groups worsened over the 18 months of the study, but the rate of decline was slower in those who received lecanemab. Also, the magnitude of the delay, while statistically significant (probably not due to chance), was small – a reduction of 0.45 on an 18-point scale.

Some experts are concerned that this effect may not be clinically relevant. In a statement to the Science Media Center, Rob Howard, a professor of age psychiatry at UCL, said that “none of the reported outcomes, including the primary outcome, reached accepted levels of improvement to constitute a clinically meaningful treatment effect.”

The success of lecanemab was also measured by the amount of amyloid and tau protein in those taking the experimental drug compared to those receiving the placebo infusion. The results showed a reduction in these proteins in those who received lecanemab.

Indeed, levels of amyloid in the brain were reduced below the threshold necessary for a positive diagnosis of Alzheimer’s disease. However, markers of brain cell death were not affected, indicating that amyloid in Alzheimer’s disease is just one mechanism in a complicated disease landscape.

Clumps of amyloid form on brain cells.
Clumps of amyloid form on brain cells.
nobeastsofierce Science / Alamy Stock Photo


About one in four participants (26.6%) in the lecanemab group experienced brain swelling or bleeding in the brain (which can be either minor or major). STAT, a medical news website, reported that a man died of a cerebral hemorrhage after receiving lecanemab, citing a possible interaction with his blood-thinning medication.

A short time later, Science magazine reported that a test patient had died for a second time, also after being treated for a stroke. However, the drug’s developer, Eisa, told Science, “All available safety information indicates that lecanemab therapy is not associated with an increased risk of death in general or from any specific cause.”

Nevertheless, given the possibility of patients taking the drug for the rest of their lives, more research on safety and interactions with existing drugs is needed.

It’s also important to find out how long the improvements in cognition last and whether the drug continues to slow the rate of decline, or whether the results stabilize — or even decline.

It should be noted that only patients with sufficient levels of amyloid detected in the brain or spinal fluid – requiring a PET brain scan or an invasive lumbar puncture – were eligible to participate in this Phase 3 study. In the UK, Alzheimer’s disease is currently diagnosed through an interview with a doctor. Dr. Susan Kohlhaas, director of research at Alzheimer’s Research UK, says the NHS is not ready for a new era of dementia treatment.

We estimate that unless there are drastic changes in the way people access specialized diagnostic tests for Alzheimer’s disease, only 2% of people eligible for drugs like lecanemab will be able to use them.

Restructuring NHS dementia services to offer routine and timely PET scans or lumbar punctures would be a costly and lengthy process.

Based on previous results, Eisai applied to the US drug regulator (the Food and Drug Administration) for accelerated approval of their drug. A decision is expected by January 6, 2023. If accelerated regulatory approval is granted, these latest results are likely to support an application for full approval.

Uncharted Brain, podcast series

Listen to The Conversation’s Uncharted Brain: Decoding Dementia podcast series to learn about the latest research unlocking clues to the ongoing mystery of how dementia works in the brain. Find all episodes via The Anthill podcast.

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