How well does Kisunla work?

In studies, treatment with Kisunla significantly slowed Alzheimer's disease clinical decline when compared to a group who received a placebo. People with the least advanced disease experienced the strongest outcomes, with a 35% slowing of decline on the iADRS score, which measures memory, thinking, and daily functioning.

Overview

On July 2, 2024 Eli Lilly announced the approval of Kisunla (donanemab-azbt), an amyloid beta-directed monoclonal antibody used to treat people with early symptoms of Alzheimer’s disease. Treatment with Kisunla should be started in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was studied.

Kisunla (donanemab-azbt) is a humanized IgG1 antibody that targets a modified form of beta amyloid plaque called N3pG. Kisunla is thought to work by helping the body remove the excessive buildup of amyloid plaques in the brain.

Study results with Kisunla

FDA approval for Kisunla was based on the 18 month, Phase 3, placebo-controlled TRAILBLAZER-ALZ 2 study with 1,736 patients with less advanced disease (low to medium tau protein levels) or the overall combined population (low/medium + high tau protein levels).

The patients had confirmed presence of amyloid pathology and mild cognitive impairment or mild dementia stage of disease.

Patients were randomized to receive 700 mg Kisunla every 4 weeks for the first 3 doses, and then 1400 mg every 4 weeks or placebo for up to 72 weeks. At Week 24, Week 52, and Week 76 the treatment was switched to placebo based on a prespecified reduction in amyloid levels measured by positron emission tomography (PET).

Patients were assessed using the Integrated Alzheimer’s Disease Rating Scale (iADRS), which measures memory, thinking, and daily functioning.

Outcomes

• Treatment with Kisunla significantly slowed clinical decline when compared to a placebo at Week 76 in the overall population. People with the least advanced disease experienced the strongest outcomes, with a 35% slowing of decline on the iADRS score.
• The overall population had a 22% slowing on the iADRS score, with both groups having up to a 39% lower risk of progressing to the next clinical stage of disease.
• In addition, in the overall population Kisunla reduced amyloid plaques on average by 61% at 6 months, 80% at 12 months, and 84% at 18 months compared to the start of the study via positron emission tomography (PET).

Dosing was continued or stopped in response to observed effects on amyloid PET imaging. The percentages of patients eligible for a switch to placebo based on amyloid levels at Week 24, Week 52, and Week 76 timepoints were 17%, 47%, and 69%, respectively.

Kisunla is administered as an intravenous infusion over about 30 minutes every 4 weeks. Healthcare providers should confirm the presence of amyloid beta pathology prior to initiating treatment.

Is there a Boxed Warning for Kisuna?

Yes, Kisunla labeling carries a Boxed Warning for Amyloid Related Imaging Abnormalities (ARIA), a common side effect seen with Magnetic resonance imaging (MRI) that usually resolves with time, but rarely can be serious or life-threatening in some patients. ARIA is associated with amyloid beta-directed monoclonal antibodies such as Kisunla and Leqembi (lecanemab-irmb).

Most people who develop ARIA do not have symptoms but some people may experience a headache, dizziness, nausea, difficulty walking, confusion, vision changes, and seizures. If you have any symptoms of ARIA, you should call your healthcare provider, call 911 (in the U.S.) or go to the nearest hospital emergency room right away.

MRI scans are done before and during your treatment to check you for ARIA. You are also more at risk of ARIA if you are a homozygous apolipoprotein E ε4 gene carrier, which is a genetic risk factor. Your healthcare provider may decide to test you for this gene, which involves a simple blood test or cheek swab to test your DNA.

There are 2 main types of ARIA:

• ARIA-E (Edema): swelling in areas of the brain due to fluid and protein leakage.
• ARIA-H (Hemosiderin/Superficial siderosis): small areas of bleeding (microhemorrhage) and iron deposits within the brain. Hemosiderin is an iron-rich pigment associated with red blood cell and ferritin breakdown.

The main difference between ARIA-H (Hemosiderin) and ARIA-H (Superficial siderosis) is the area of the brain where blood leaks are seen. ARIA-H (Hemosiderin) is seen on imaging in the area of the brain known as the parenchyma (the wall of the brain), and ARIA-H (Superficial Siderosis) is blood leakage and hemosiderin build-up in the subarachnoid space near the brain surface.

Serious bleeding in the brain larger than one centimeter in size has occurred in patients treated with this class of medications.

Kisunla can also cause infusion-related reactions. Your healthcare provider can give you medicines before your infusions to help decrease the risk of an infusion reaction, if needed. Warnings and precautions also include injection-site reactions and serious allergic reactions.

Related questions

• What are monoclonal antibodies?
• How do I decide between Leqembi and Kisunla?
• What's the mechanism of action for Leqembi (lecanemab-irmb)?

How often does ARIA occur with Kisunla?

In studies, ARIA was a commonly reported adverse effect when compared to a placebo (an inactive treatment). The percentages of people that received Kisunla and had ARIA-E or ARIA-H, compared to placebo was as follows:

• ARIA-E (24% on Kisunla vs. 2% on placebo)
• ARIA-H microhemorrhage (25% vs. 11% placebo)
• ARIA-H superficial siderosis (15% vs. 3% placebo)

Other common side effects included headache (13% vs. 10% placebo) and infusion-related reactions (9% vs. 0.5% placebo).

This is not all the information you need to know about Kisunla (donanemab-azbt) for safe and effective use and does not take the place of your healthcare provider's directions. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.