Donanemab (Kisunla) 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.

Donanemab is an antibody that targets these protein deposits in the brain: It binds to the beta-amyloid protein and is thought to break down deposited protein with the help of the immune system.

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

Donanemab is only suitable for people who have early-stage Alzheimer's disease. It is not approved for people whose disease has already progressed further.

The main signs of early-stage Alzheimer's disease are problems with memory and thinking. The forgetfulness can be mild and have hardly any (or no) effect on everyday life. The medical term for this is mild cognitive impairment (MCI). But it may already be worse, making it harder to live an independent life. Then it is considered to be mild Alzheimer's dementia.

Before starting treatment with donanemab, people must have an MRI scan ( magnetic resonance imaging scan) in order to rule out other problems such as swelling or bleeding in the brain. If you would like to have treatment with donanemab, you can only do so if you agree to other conditions, too:

• You must allow your data to be collected in a European registry.
• You must agree to have regular MRI scans to see if there are any signs of problems like swelling in the brain.

Because of the possible serious side effects and special aspects of treatment with donanemab, your doctor must give you particularly thorough information. The manufacturer has produced detailed written information for this purpose. This includes a special card for patients (“Patientenpass” in German) with the most important information on donanemab and the associated risks: It is given to all people who are planning to have treatment with this medication, before the treatment starts. You should always carry the card with you and show it every time you go to a doctor's practice. The doctor will also give you the package insert for donanemab.

Doctors diagnose Alzheimer's disease if the person clearly has the typical symptoms (memory and thinking problems) and other causes are unlikely. Various standard questionnaires are used to assess memory and thinking skills.

In addition, the person must be shown to have the typical protein deposits in their brain. This is done using biomarkers. It often 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.

Donanemab can only be used in people 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 donanemab. 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 variant to their child. Depending on which variant they 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 carry the gene as well. These relatives could also have a higher risk of developing Alzheimer's disease later in life. So knowing that you have the gene can have consequences for other members of your family, too. Because of this, the doctor has to tell you all about this before you have the genetic test.

The following table shows the examinations and tests that are needed to find out whether someone can have treatment with donanemab.

In each case, you have to talk to a doctor beforehand – to discuss the potential disadvantages and risks, too. The table lists important aspects that you can talk about during that appointment:

Donanemab is given as an infusion (a drip) every four weeks. The infusion takes at least 30 minutes. After the infusion, you will be monitored for at least another 30 minutes to see if you have any negative reactions to it.

The first infusion contains 350 mg donanemab, the second contains 700 mg, the third contains 1,050 mg, and all infusions after that contain 1,400 mg donanemab.

The person must have MRI scans during treatment with donanemab: before the 2^nd, 3^rd, 4^th and 7^th infusion. The scans are done to look for signs of swelling or bleeding in the brain. People who have risk factors (like a copy of the ApoE4 gene variant, or previous swelling or bleeding in the brain) also have an MRI scan before their 12^th infusion (one year after the start of treatment). More MRI scans are done if there are symptoms such as headaches, confusion, nausea, vision problems, dizziness or difficulty walking.

Treatment with donanemab should not last longer than 18 months. It ends sooner if no more amyloid plaques can be found in the brain.

Treatment with donanemab 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 regularly, along with other signs of Alzheimer's.

Doctors will also consider temporarily or permanently stopping the treatment if there is any swelling or bleeding in the brain during the treatment.

In 2026, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into whether donanemab has advantages or disadvantages (compared to the previous standard treatments) in people with early-stage Alzheimer's disease who meet the necessary criteria to be able to have treatment with donanemab.

The standard treatment for mild cognitive impairment is active surveillance (a "wait-and-see" approach with check-ups). For people with mild Alzheimer's dementia, treatment with the medications donezepil, galantamine or rivastigmine is recommended.

But the manufacturer didn’t provide any suitable data with which to do the assessment.

This information summarizes the main results of a review produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The review was commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of this review and the hearings received, the G-BA will pass a resolution on the added benefit of donanemab (Kisunla).