The Alzheimer’s drug donanemab (trade name Kisunla) has been given the green light by the Committee for Medicinal Products for Human Use (CHMP). The expert committee of the European Medicines Agency (EMA) has recommended approval of the active substance for the treatment of Alzheimer’s disease in people in the early stages of the disease. However, approval is to be restricted to patients with no more than one copy of the ApoE4 gene variant. The background to this is that patients with a double ApoE4 copy have a higher risk of side effects. This makes Kisunla the second Alzheimer’s antibody, alongside Leqembi, that is expected to be approved as a drug in the EU.

In March, the committee had still spoken out against the active substance – citing excessive side effects. The manufacturer, Lilly, then applied for a re-examination. The final decision on approval lies with the European Commission.

In April, the European Commission approved the active ingredient lecanemab (trade name Leqembi), which has a similar effect to Kisunla. Both active ingredients have now been approved for the treatment of early-stage Alzheimer’s patients in countries including the USA, Japan, China and the UK.

Statement by Dr. Anne Pfitzer-Bilsing (Head of Science at the non-profit Alzheimer’s Research Initiative AFI):

“Following the approval of Leqembi, the CHMP’s vote on Kisunla comes as no surprise. This is a good decision for science and research. It is also good news for a small group of patients. However, Kisunla does not provide a cure either, but can only delay the course of the disease by a few months. Even if the effect of Kisunla is somewhat greater than that of Leqembi, we are still talking about a small effect. This is certainly not what people with Alzheimer’s ultimately hope for from a new drug. Nevertheless, we are of course delighted for patients who have been given a few valuable months of time with Kisunla.

Unfavorable risk-benefit ratio

The minor effect is offset by potentially serious side effects. Almost 37 percent of the test subjects experienced brain swelling and cerebral hemorrhages, some of which were severe. This means that Kisunla performed worse than Leqembi in terms of side effects. Fatalities were reported for both active substances in connection with the approval studies. We therefore expressly welcome the Committee’s recommendation to exclude patients with a double ApoE4 gene because they have a higher risk of side effects. The Committee’s recommendation that access to Kisunla treatment should be via a central registry will also contribute to the safety of the treatment.

Only a small group of people are eligible for treatment

It is important that we do not give patients false hope. Only a very small group of patients can benefit from the treatment. Kisunla is only suitable for patients at a very early stage of the disease who have only suffered very mild mental impairment. People with advanced Alzheimer’s disease or other dementia are not eligible for treatment.

The therapy is complex. Various preliminary examinations are necessary to determine whether Kisunla can even be considered. Regular MRI examinations are required to detect possible side effects at an early stage. Patients must therefore be mobile and physically resilient.

Important progress for research

Despite the aforementioned limitations in practical application, the development of the two antibodies donanemab and lecanemab represents an important step forward in Alzheimer’s research. For the first time, the two active substances successfully attack one of the possible causes of the disease. They eliminate the harmful deposits of amyloid-beta, which are associated with the death of nerve cells in Alzheimer’s disease. Until now, Alzheimer’s could only be treated symptomatically with so-called anti-dementia drugs.

If donanemab is also approved after lecanemab, we can now gather practical and further scientific experience. This could help us to further develop the active substances and perhaps also get a better grip on the side effects. Nevertheless, this will not be enough. Alzheimer’s disease is very complex and we must therefore continue to research other possible causes of the disease.

Alzheimer’s cure through combination therapies

In order to cure Alzheimer’s, a combination therapy will be needed that is tailored to the individual clinical picture of the patient. Another therapeutic target could be deposits of tau proteins, which also contribute to the death of nerve cells in Alzheimer’s disease. We also see promising research approaches in inflammatory processes in the brain, metabolic or circulatory disorders, genetic changes or the intestinal microbiome. Unfortunately, the road to a cure is still long – despite the latest research successes.”

The most important questions and answers:

Who is Kisunla suitable for?

Treatment with Kisunla is probably only an option for a small group:

• People with mild cognitive impairment (MCI) with Alzheimer’s disease
• People in the early stages of Alzheimer’s dementia
• Patients who have at most one copy of the ApoE4 gene
• As the treatment is time-consuming and involves extensive examinations, patients must also be mobile and sufficiently resilient.

Who cannot be treated with Kisunla?

• Patients with a double copy of the ApoE4 gene (higher risk of side effects)
• Patients in an advanced stage of Alzheimer’s disease
• People with other dementias

Which examinations are carried out?

Whether treatment is an option must be decided on an individual basis together with the doctor. The following examinations are likely to be used, among others:

• Nerve fluid examination and imaging:

In order to detect the harmful beta-amyloid deposits in the brain, either a cerebrospinal fluid examination or special imaging (amyloid PET) is carried out.

• Genetic test:

A blood test is used to check whether no or at most one copy of the ApoE4 gene is present.

How is the treatment likely to proceed?

Because the therapy is only effective at an early stage, patients must be diagnosed as early as possible. Treatment can probably only be carried out in university hospitals and specialized practices that have the necessary expertise and technical equipment.

• How and how often is the medication administered?

Kisunla is administered intravenously as an infusion every four weeks. The administration itself takes about 30 minutes.

• How long does the treatment take?

The duration of treatment varies from person to person and is continued until sufficient amyloid plaques have been removed from the brain. In medical studies, this took between six and 18 months.

• How are the side effects monitored?

Regular MRI examinations are planned in order to detect possible side effects such as brain swelling or bleeding at an early stage. If serious side effects occur, treatment must be suspended.

Further information:

Kisunla | European Medicines Agency (EMA)

Alzheimer’s disease (Alzheimer’s disease) | Alzheimer Forschung Initiative e.V. (AFI)

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Gender note. The personal designations used in this text always refer equally to female, male and diverse persons. Double/triple references and gendered designations are avoided for the sake of better readability ected.