Leqembi vs Kisunla
How Leqembi and Kisunla compare as anti-amyloid infusions for early Alzheimer's disease.
How they're similar
Leqembi and Kisunla are more alike than they're different. Both are humanized monoclonal antibodies designed to clear amyloid from the brain, and both are approved for the same patient group: people with early Alzheimer's, meaning mild cognitive impairment or mild dementia due to Alzheimer's, with confirmed amyloid on imaging or spinal fluid.
- Both work by binding to forms of beta-amyloid and prompting the immune system to clear it.
- Both are given by IV infusion in an outpatient setting.
- Both require baseline MRI and repeat MRIs during treatment to watch for amyloid-related imaging abnormalities.
- Both carry a boxed warning for ARIA and infusion reactions.
- Both need APOE4 genotyping before starting, since APOE4 homozygotes have a much higher risk of ARIA.
- Both are not appropriate for people with moderate or severe dementia, or for people without confirmed amyloid pathology.
- Both slow cognitive and functional decline modestly. Neither reverses the disease or stops it.
The overall approach is the same. Confirm amyloid, screen for risk factors, start infusions, monitor with MRIs on a schedule, and pause or stop if imaging changes cross a threshold. Whether the modest benefit is worth the burden and risk is a real conversation, and reasonable clinicians and families land in different places on that question.
How they differ
The differences are in target, dosing schedule, duration of therapy, and MRI schedule.
| Leqembi (lecanemab) | Kisunla (donanemab) | |
|---|---|---|
| Manufacturer | Eisai and Biogen | Eli Lilly |
| FDA approval | January 2023 | July 2024 |
| Amyloid target | Soluble amyloid protofibrils | Plaque-specific pyroglutamate amyloid |
| Infusion schedule | Every two weeks | Every four weeks |
| Duration of therapy | Indefinite, or until disease progresses | Can be stopped once amyloid PET shows clearance, often at 12 to 18 months |
| MRI schedule | Baseline and before doses 5, 7, and 14 | Baseline and before doses 2, 3, 4, and 7 |
| Trial that supported approval | Clarity AD | TRAILBLAZER-ALZ 2 |
| Relative slowing of decline on CDR-SB | About 27% | About 35% |
Both drugs target amyloid, but they hit different pieces of it. Leqembi binds preferentially to soluble amyloid protofibrils, which are thought to be an especially toxic form on the pathway to plaque. Kisunla binds a specific modified amyloid found in mature plaques. Whether that mechanistic difference translates into real clinical differences in individual patients is still being sorted out. Kisunla showed a somewhat larger effect on the primary outcome in its approval trial, but the two drugs haven't been compared head to head, and cross-trial comparisons need caution.
The dosing schedule matters for the family logistics. Leqembi is every two weeks, which means about 26 infusions a year. Kisunla is every four weeks, which cuts that roughly in half. Each infusion takes about an hour, plus transport time, waiting room time, and observation time. Over a year, the difference is substantial.
Duration of therapy is the biggest structural difference. Leqembi is intended to be continued indefinitely, as long as it's tolerated and the person hasn't progressed to moderate dementia. Kisunla is unique in that it can be stopped once amyloid PET imaging shows the plaques have been cleared, typically at 12 to 18 months. That's a defined endpoint some families find appealing, since it puts a boundary on the treatment.
The MRI schedules are different because ARIA tends to show up at different points in each drug's course. Leqembi's protocol requires MRIs before doses 5, 7, and 14. Kisunla's protocol front-loads MRIs before doses 2, 3, 4, and 7, since ARIA tends to appear earlier in treatment on Kisunla.
Side effect tendencies
The main safety issue for both drugs is ARIA, which stands for amyloid-related imaging abnormalities. ARIA comes in two flavors. ARIA-E is edema, or swelling in the brain, and ARIA-H is hemorrhage, meaning small areas of bleeding or microhemorrhage. Both are found on MRI, and most cases are asymptomatic. Some people, though, develop headache, confusion, dizziness, visual changes, or seizures, and a small number of cases are serious or fatal.
ARIA risk is much higher in APOE4 homozygotes, meaning people who inherited the APOE4 gene variant from both parents. Rates in that group can exceed 30 percent on either drug. Heterozygotes and non-carriers have lower rates. Because of that, APOE genotyping is now standard before starting either drug. Families are counseled on the added risk if the person is a homozygote, and some homozygotes and their families decide against treatment for that reason.
Infusion reactions are common with both drugs, and more common with Leqembi. Symptoms include fever, chills, nausea, body aches, and changes in blood pressure. Premedication can help, and most reactions are manageable.
Other risks include hypersensitivity reactions and, rarely, hemorrhage that's more than microhemorrhage. Anticoagulation is a real concern. Both drugs carry warnings about the increased risk of serious brain bleeding in people on blood thinners, and the decision to start one of these medications in someone on anticoagulation is complex.
What tips the choice
Family logistics tip the choice more than most people expect. Leqembi's every-two-weeks schedule is a big time commitment, and Kisunla's every-four-weeks schedule is easier on families who are already stretched thin. If a family can only realistically make one infusion trip a month, that alone can decide it.
The endpoint matters too. Kisunla's ability to stop once amyloid is cleared appeals to families who want a defined treatment course. Leqembi's indefinite approach appeals to some clinicians who want ongoing amyloid coverage.
Baseline MRI findings can shift the decision. If someone already has significant microhemorrhages on baseline imaging, some clinicians lean toward the drug with the less aggressive early ARIA profile, but both drugs have clear thresholds where treatment can't proceed safely.
APOE4 status matters. Homozygotes carry the highest ARIA risk on both drugs, and some families decide against either treatment because of that. Heterozygotes are intermediate. Non-carriers have the lowest risk.
Stage of disease is a hard boundary. Neither drug is appropriate for moderate or severe Alzheimer's. Both are for MCI or mild dementia with confirmed amyloid pathology. If someone has already progressed beyond that stage, these drugs aren't an option.
Anticoagulation is a strong caution against either drug. In someone on warfarin, a DOAC, or dual antiplatelet therapy, the bleeding risk needs a careful look.
Cost and coverage are real. Both drugs are expensive, and Medicare coverage requires enrollment in a national registry and use of the drug in accordance with the label. Confirming amyloid pathology, either by PET or CSF, is a required step, and access to those tests varies.
Common questions
Do these drugs actually help? They slow the rate of decline modestly in the trials. Clarity AD showed about 27 percent relative slowing on the CDR-SB scale for Leqembi. TRAILBLAZER-ALZ 2 showed about 35 percent for Kisunla. Whether that's clinically meaningful to any given person and family is a fair question, and there's real debate about it. Neither drug reverses symptoms.
What is ARIA and how worried should we be? ARIA stands for amyloid-related imaging abnormalities. It's a set of MRI findings that come with amyloid clearance and can include swelling or small bleeding. Most cases are asymptomatic and are picked up on protocol MRIs. Some cases cause headache, confusion, or worse, and a small number are serious or fatal. APOE4 homozygotes have the highest risk. The MRI schedules exist to catch ARIA early before it becomes symptomatic.
Can these drugs be given for moderate or severe Alzheimer's? No. Both are approved for early Alzheimer's only, meaning mild cognitive impairment or mild dementia stage. Once someone has progressed to moderate or severe dementia, these drugs are not appropriate. The trials didn't include those patients, and the risk-benefit balance is different there.
Why does APOE genotyping matter? APOE4 is a genetic variant that raises the risk of both Alzheimer's disease and ARIA. Homozygotes, meaning people with two copies of APOE4, have the highest ARIA rates on these medications. Because of that, both drug labels recommend testing APOE status before starting, so families can make an informed decision about risk.
Can I take Leqembi or Kisunla with donepezil or memantine? Yes. The anti-amyloid antibodies work on the disease process, and the symptomatic medications work on cholinergic and glutamate systems. They target different problems and can be used together. Whether a family wants to add more medications is a separate conversation with the prescriber.
Sources
This guide draws on current prescribing information and public health references. It is reviewed for clinical accuracy and updated as guidance changes. This is not medical advice.
- U.S. Food and Drug Administration. Lecanemab (Leqembi) prescribing information.
- U.S. Food and Drug Administration. Donanemab (Kisunla) prescribing information.
- Alzheimer's Association. Anti-amyloid treatments for Alzheimer's disease.
- National Institute on Aging. Alzheimer's disease treatment resources.
Managing a medication needs a prescriber
Any psychiatric medication has to be started and adjusted by a clinician who can follow you over time. If you don't have a prescriber, our guides section explains the options, including in-person care and telepsychiatry, and how to choose between them.