The drug, Donanemab, otherwise known as Kisunla, represents a significant step forward in the management of Alzheimer’s disease, as it is one of the first licensed treatments that can slow down the progression of the disease. The drug is now offering hope to those in the early stages of this challenging condition.
However, due to the way it works and potential side effects, it will not benefit everyone and as a result, patients need to meet certain criteria before they can be offered this therapy.
It is also important to stress that Donanemab may slow the progression of cognitive decline, but it is not a cure for Alzheimer’s disease.
Consultant neurologist Cath Mummery has provided an outline of the drug and the very strict eligibility criteria for patients.
How does Donanemab work?
Donanemab is a disease-modifying therapy which targets amyloid-beta protein plaques in the brain. These plaques accumulate in the brains of people with Alzheimer's disease and affect the way the nerve cell messages get through, interfering with memory and other cognitive functions. Donanemab is an antibody that recognises and attaches to amyloid which forms these plaques; it then induces the removal of these plaques leading to a lowering of levels of amyloid in the brain. This has been shown to slow down the progression of Alzheimer's Disease to some degree, although it should not be seen as a cure.
Patients need to have an intravenous transfusion of the drug every 4 weeks for the course of treatment.
In a proportion of patients, side effects may occur. Patients will be monitored with regular MRI brain scans and clinical checks to ensure there are no issues. Usually these side effects, known as ARIA (focal brain swelling or small brain bleeds) do not cause any symptoms and resolve after the drug is paused for a few weeks. However, occasionally symptoms can occur and on rare occasions a patient might need to be admitted for treatment.
Eligibility criteria for Donanemab
Because of the way the drug works and its specific effects on the body, not every Alzheimer’s patient is suitable for this treatment option. Patients will need to meet very strict criteria in order to be eligible.
Donanemab is intended for individuals in the early stages of Alzheimer’s disease, including those diagnosed with mild cognitive impairment (MCI) due to Alzheimer’s, or mild dementia due to Alzheimer’s disease. This stage usually presents as noticeable, but not severe issues with memory loss. The patient may also have difficulties completing some daily tasks, but the challenges are not significant enough to get in the way of day-to-day living.
Patients must have confirmed evidence that there are signs of amyloid-beta plaques in their brain. This can be detected via brain scans (amyloid PET) or through the analysis of their spinal fluid via a lumbar puncture As Donanemab targets amyloid protein specifically, the drug will not be effective if there is no evidence that the amyloid-beta protein is present.
Patients should not have other significant neurological disorders that could interfere with the diagnosis or treatment of Alzheimer’s disease. Conditions such as Lewy body dementia, frontotemporal dementia, or cerebrovascular diseases may require different treatment options in their own right, and the drug would be unlikely to be of benefit.
APOE4 is a gene which is increases the risk for developing late-onset Alzheimer's disease. For patients who have inherited two copies of the gene, the risk is even higher and therefore considered not suitable as risks of treatment outweigh the benefit. All patients will be screened for APOE4 (blood test) as part of the eligibility decision-making process.
Patients with a history of large brain haemorrhages are at a higher risk of negative side effects like brain swelling if they take Donanemab.
Donanemab is not suitable for patients who take medicines to reduce the risk of, or prevent blood clots from forming.
Uncontrolled high blood pressure can also cause complications in patients if they use Donanemab, so it is important that this is well controlled before the drug can be prescribed. Negative effects can include an increased risk of brain swelling and small brain bleeds.
Donanemab requires close monitoring. Regular MRI scans and clinical assessments are needed to check on side effects and any impact on the brain. Patients will need to commit to these regular hospital trips.
At the current time, Donanemab has been successfully trialled in patients aged 60 to 85. For older patients in particular, overall health would need to be taken into consideration as well. Patients who are dealing with a significant amount of other health issues or who are generally frail might not be suitable for this drug as there are additional risks associated with the side effects.
As with all medical treatment, patients and their caregivers will need to give informed consent to ensure that they understand the benefits, risks and limitations of their treatment, and this conversation will need to take place with a chosen consultant before the drug can be administered.
If you think you or your loved one would fit the criteria for Donanemab and you would like to enquire about treatment, please email the team at uclh.
