Lecanemab (Leqembi) for early-stage Alzheimer's disease

In Alzheimer's disease, more and more nerve cells in the brain die as time goes by. Deposits of small protein particles (known as amyloid plaques) are also found in the brains of those affected. Some experts suspect that these protein deposits damage the nerve cells.

Lecanemab is an antibody that targets these protein deposits in the brain: It binds to the beta-amyloid protein and is thought to prevent the build-up of further deposits in this way. With the help of the immune system, it is also thought to partially break down protein that has already been deposited.

These effects of the medication are believed to slow down the progression of the disease. But lecanemab cannot cure Alzheimer's or stop the disease from progressing overall.

Lecanemab is only suitable for people who have early-stage Alzheimer's disease. It is not suitable in later stages.

The main signs of early-stage Alzheimer's disease are problems with memory and thinking. The forgetfulness can be mild and have (almost) no effect on everyday life. But it may already be worse, making it harder to live an independent life. Experts distinguish between mild cognitive impairment (MCI) and mild Alzheimer's dementia.

Before starting treatment with lecanemab, people must have an MRI scan ( magnetic resonance imaging) in order to rule out other problems such as swelling or bleeding in the brain. Patients who meet the above criteria can only use lecanemab if they agree to other conditions, too:

• Anyone who uses the medication in Europe must allow their data to be collected in a registry. That way, scientists can find out how often side effects occur, for example. So people who meet the described criteria and would like to have the treatment must agree to have their data passed on to this registry.
• Patients must also agree to have regular MRI scans in order to see if there are any signs of problems like swelling in the brain.

Before lecanemab is allowed onto the market, the manufacturer has to produce written information about the medication, including a special card for patients. This card must be given to the patient before the treatment is started.

Alzheimer's disease is diagnosed if the person clearly has the typical symptoms (impaired memory and thinking problems) and other causes are unlikely.

In addition, they must be shown to have the typical protein deposits in their brain. This is done using biomarkers. It usually involves taking a sample of cerebrospinal fluid through a lumbar puncture (spinal tap). But it can also be done using amyloid positron emission tomography (amyloid PET imaging). Amyloid PET is an imaging technique that uses a weak radioactive substance to see beta-amyloid protein deposits in the brain.

Lecanemab can only be used in patients with early-stage Alzheimer's disease who have a maximum of one copy of a specific version of a gene, known as ApoE4. This is because people who have two copies of ApoE4 (rather than only one copy, or no copies) are more likely to have serious side effects when using lecanemab. These include potentially life-threatening swelling and bleeding in the brain.

We all have two copies of the ApoE gene. It plays a role in fat metabolism. But there are three different versions (variants) of the gene, known as E2, E3 and E4. Each of the parents passes on one copy to their child. Depending on which variants of the gene the parents pass on, their child might have one, two or no copies of the E4 variant.

Doctors can use a genetic test to find out whether the person has any copies of the ApoE4 gene variant – and if so, how many. This is done by taking a sample of blood and examining it in a laboratory. The genetic test is not yet a routine test.

Research has shown that people are more likely to get Alzheimer's disease (at a younger age, too) if they have two ApoE4 genes rather than just one ApoE4 gene and one ApoE3 gene, for example. If someone is found to have the ApoE4 gene, it could be a good idea to find out whether, for example, their children and siblings also carry the gene and have a higher risk of developing Alzheimer's later on. Knowing that you have the gene can also have consequences for other members of the family. So the doctor has to tell their patient all about this before they have the genetic test.

Lecanemab is given as an infusion (a drip) every two weeks. The infusion takes about one hour.

The dosage depends on the person's body weight (10mg of lecanemab per kilogram of body weight). For the infusion, the drug is diluted with 250 ml of saline solution (0.9%).

The person must have MRI scans during treatment with lecanemab: before the 5^th, 7^th and 14^th dose.

These scans are done to look for signs of swelling or bleeding in the brain. More MRI scans are done if there are symptoms such as headaches, confusion, nausea, vision problems, dizziness or difficulty walking.

Treatment with lecanemab is stopped if the disease progresses to middle-stage (moderate) Alzheimer's dementia. To be able to assess this, the person's memory and thinking skills are tested about every 6 months, along with other signs of Alzheimer's.

Doctors will also consider stopping the treatment if there is an increased risk of bleeding in the brain during the treatment. This may be the case, for example, if the person needs treatment with an anticoagulant or a thrombolytic (a drug designed to dissolve blood clots).

In Germany, the pros and cons of lecanemab (compared to treatments that are already being used) will be examined more closely once lecanemab becomes available. This is because new drugs undergo something known as an early benefit assessment after they enter the German market. Here, the Joint Federal Committee (G-BA) commissions the Institute for Quality and Efficiency in Healthcare (IQWiG) to scientifically assess the drug's pros and cons for patients, compared to the current standard treatments. For this purpose, manufacturers must provide all the data they have on a new drug – including previously unpublished research results.

The results of the research on lecanemab are expected to be published in the summer of 2025 and will then be included in this article. These results will help people to make an informed decision about whether or not to have treatment with lecanemab.