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Is Lecanemab the Drug that can Finally Make the Difference for Dementia?

Tuesday, December 13th, 2022

The dementia world has been stirred by a recent paper reporting the drug Lecanemab’s effect on slowing cognitive decline in people with early Alzheimer’s Disease[1].

In Alzheimer’s disease, two key proteins – tau and amyloid beta – build up into tangles and plaques, and cause brain cells to die. The human body naturally produces antibodies to defend itself from infection. Lecanemab is an antibody that binds to amyloid and stimulates the immune system to destroy it. Many drugs have been designed to clear amyloid, but they have not shown the anticipated corresponding benefit on cognition – until now.

In the recent robust clinical trial, 1795 people aged between 50-90 years old with mild cognitive impairment or early Alzheimer’s disease, were randomly assigned to receive an infusion of Lecanemab once every 2 weeks or a matched placebo. Participants also had to show evidence of amyloid on a brain scan or cerebrospinal fluid testing. Participants were assessed for the severity of their symptoms using a battery of memory, problem-solving, and other cognitive tests, as well as interviews with their caregivers and doctors. After 18 months of treatment, brain studies for those receiving Lecanemab showed a reduction in amyloid and their symptom scores had declined 27 per cent less than those in the placebo group.

Only a modest effect

The results sound promising. However, some question whether the effect is big enough to make a noticeable difference in a person’s symptoms to the naked eye. Lecanemab participants scored, on average, 0.45 points better on the18-point cognitive rating scale than those who received the placebo. Researchers have estimated that to make a meaningful difference to people’s lives, any treatment would need to improve the score to one point on the scale.

Risk versus Benefit

Another problem is safety. People with Alzheimer’s disease have amyloid in their blood vessels as well as their brain. While Lecanemab removes amyloid from the brain, it also removes it from blood vessels in the brain. This can make the blood vessels leaky. Indeed, swelling and bleeding on the brain occurred in 21% of those given Lecanemab versus 9% of those given the placebo.

Reality Check

People can be monitored with periodic brain scans to make sure the swelling does not take off. However, this raises the second issue – cost and feasibility. Many health systems would lack the infrastructure to facilitate fortnightly drug infusions, brain imaging to determine treatment eligibility, plus regular scanning to look out for any brain swelling. It sounds prohibitive for low-income and middle-income countries—where most people with dementia live. Moreover, the drug only targets those in the early stages of dementia with a certain level of amyloid build-up, limiting the number of people who could potentially use the treatment Amyloid is only one component of Alzheimer’s disease too. The detrimental second protein called tau also needs to be addressed.

Watch this space

The US Food and Drug Administration is expected to approve Lecanemab in January. In Australia, the Therapeutic Goods Administration is more cautious[2]. The recent finding that Lecanemab, can slow Alzheimer’s cognitive decline is a long way short of declaring a cure, but it does represent an encouraging qualitative shift in the decades-long search for a treatment. For now, the key public health message for Alzheimer’s disease continues to be, target the modifiable risk factors for dementia—such as hypertension, smoking, diabetes, and obesity—to maintain brain health across the lifespan.[3]