Kisunla

Approved Indications

Kisunla is used to treat Alzheimer's disease in patients who are in the early symptomatic stages of the condition. This includes individuals diagnosed with:

• Mild cognitive impairment (MCI): A stage where memory or thinking issues are noticeable but have not yet caused significant impairment in daily functioning.
• Mild dementia: The early stage of Alzheimer's disease where symptoms begin to interfere with some daily activities.

Clinical Requirements

Treatment with Kisunla is only appropriate for patients who have confirmed amyloid plaques in the brain. Healthcare providers must verify the presence of these plaques through diagnostic testing, such as a PET scan or a lumbar puncture (spinal tap), before starting the medication.

Goals of Treatment

The primary purpose of Kisunla is to slow the progression of cognitive and functional decline in people with early Alzheimer's. By targeting and removing amyloid plaques, the medication aims to help patients maintain their independence and cognitive abilities for a longer period.

Limitations of Use

Kisunla has not been studied and is not indicated for patients in the more advanced stages of Alzheimer's disease, such as moderate or severe dementia. It is specifically intended for those in the earliest symptomatic phases of the disease.

Targeting Amyloid Plaques

In people with Alzheimer's disease, a protein called amyloid-beta clumps together to form plaques in the brain. These plaques are believed to interfere with how brain cells communicate and contribute to the loss of cognitive function over time.

How the Medication Works

Kisunla is a monoclonal antibody, which is a type of protein designed in a laboratory to recognize and bind to specific targets in the body. This medication specifically targets the amyloid-beta plaques that have already formed in the brain. Once Kisunla attaches to these plaques, it helps the body's immune system identify and remove them.

Slowing Disease Progression

By reducing the buildup of amyloid plaques, Kisunla is intended to slow the decline of memory and thinking skills. It also aims to help patients maintain their ability to perform daily activities for a longer period. The treatment is specifically for individuals in the early stages of Alzheimer's disease, including those with mild cognitive impairment or mild dementia.

Unlike some other treatments, Kisunla may be stopped once brain imaging shows that a significant amount of plaque has been cleared from the brain.

Common Side Effects

The most common side effects reported by people taking Kisunla include:

• Headache
• Infusion-related reactions, which may cause symptoms like nausea, vomiting, sweating, or changes in blood pressure

Serious Side Effects

A serious side effect associated with Kisunla is Amyloid-Related Imaging Abnormalities (ARIA). ARIA most commonly presents as temporary swelling in areas of the brain or small spots of bleeding on the brain's surface. While ARIA often does not cause symptoms, it can sometimes be serious or life-threatening. Symptoms of ARIA may include:

• Confusion or disorientation
• Dizziness
• Vision changes
• Nausea
• Seizures
• Difficulty walking

Other serious side effects can include severe allergic reactions during the infusion. Patients are typically monitored for signs of a reaction, such as hives, rash, or trouble breathing, during and after the administration of the drug.

Amyloid-Related Imaging Abnormalities (ARIA)

Kisunla can cause amyloid-related imaging abnormalities, or ARIA. This condition involves temporary swelling in areas of the brain (ARIA-E) or small spots of bleeding in or on the surface of the brain (ARIA-H). While many people do not experience symptoms, ARIA can be serious or even life-threatening.

Symptoms of ARIA may include:

• Headache
• Confusion or disorientation
• Dizziness
• Vision changes
• Nausea
• Difficulty walking
• Seizures

Healthcare providers typically perform MRI scans before starting treatment and periodically during the first several months of therapy to monitor for ARIA. If ARIA is detected, treatment may need to be paused or discontinued depending on the severity.

Genetic Risk Factors

People who carry two copies of the ApoE ε4 gene allele have a higher risk of developing ARIA compared to those who do not. Testing for this gene is recommended before starting Kisunla to help assess the risk of these complications.

Infusion-Related Reactions

Some people may experience reactions during or after the intravenous infusion. These reactions can range from mild to severe. Symptoms may include:

• Chills or shivering
• Redness or flushing of the skin
• Nausea or vomiting
• Changes in blood pressure
• Shortness of breath
• Anaphylaxis (a severe, life-threatening allergic reaction)

If an infusion reaction occurs, the healthcare provider may slow or stop the infusion and provide appropriate medical care.

Pregnancy

It is unknown whether Kisunla can cause harm to an unborn baby. Because Alzheimer's disease primarily affects older adults, there is no information from clinical trials about the drug's effects on pregnant individuals. If you are pregnant or planning to become pregnant, you should discuss the potential risks and benefits of this treatment with your healthcare provider.

Breastfeeding

It is not known if Kisunla passes into human breast milk or if it has any effect on a nursing infant. Because many medications can be excreted in breast milk, it is important to talk to your doctor about the risks and the best way to feed your baby while receiving this medication.

Available Forms

Kisunla is supplied in the following form:

• Intravenous Injection: A sterile, clear to opalescent, colorless to slightly yellow solution provided in a single-dose vial.

This medication is administered as an infusion into a vein. It is provided as a concentrate that must be diluted by a healthcare professional before it is given to the patient.

FDA Approval Status

The U.S. Food and Drug Administration (FDA) approved Kisunla in July 2024. It is indicated for patients with early symptomatic Alzheimer’s disease, which includes individuals with mild cognitive impairment or those in the mild dementia stage of the disease. Treatment is appropriate only for patients with confirmed amyloid pathology in the brain.

Boxed Warning

Kisunla includes a Boxed Warning regarding Amyloid-Related Imaging Abnormalities (ARIA). ARIA most commonly presents as temporary swelling in areas of the brain (ARIA-E) or small spots of bleeding in or on the surface of the brain (ARIA-H). While ARIA often does not cause symptoms, it can lead to serious or life-threatening events. Symptoms may include headache, confusion, dizziness, vision changes, or seizures.

Monitoring and Safety Requirements

• MRI Monitoring: Healthcare providers must obtain a baseline brain MRI before starting treatment. Periodic follow-up MRIs are required during treatment to monitor for the development of ARIA.
• ApoE ε4 Genotyping: Testing for ApoE ε4 status should be performed prior to initiation. Patients who are homozygous for the ApoE ε4 allele have a higher observed incidence of ARIA compared to heterozygotes and non-carriers.
• Infusion Reactions: The FDA labeling includes warnings for infusion-related reactions, which can include flu-like symptoms, nausea, vomiting, and blood pressure changes.

Clinical Trial Basis

The approval was supported by data from the TRAILBLAZER-ALZ 2 clinical trial, a double-blind, placebo-controlled study. The trial demonstrated that Kisunla significantly slowed clinical and functional decline in patients with early symptomatic Alzheimer’s disease compared to those receiving a placebo.

Withdrawal and Discontinuation

There is currently no evidence that Kisunla (donanemab-azbt) causes withdrawal symptoms or physical dependence. Monoclonal antibodies used for Alzheimer's disease do not typically lead to physical cravings or illness when the medication is discontinued.

A unique aspect of Kisunla treatment is that it is not necessarily intended to be lifelong. Clinical trials showed that treatment could be stopped once amyloid plaques in the brain reached very low levels, as measured by PET scans. Your healthcare provider will monitor your progress and determine when it is appropriate to pause or end the infusions.

If you miss a dose or decide to stop treatment, you should contact your healthcare provider. While stopping the drug does not cause a withdrawal syndrome, it will stop the medication's effect on clearing amyloid plaques from the brain.