Monoclonal Antibodies For Alzheimer’s: How Leqembi And Kisunla Work

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Leqembi and Kisunla are FDA-approved antibodies for early symptomatic Alzheimer’s that help the immune system remove forms of beta-amyloid from the brain. Trials found modest slowing of cognitive and functional decline, but the drugs do not restore lost memory, carry risks including brain swelling and bleeding, and their longer-term effects remain uncertain.

Leqembi and Kisunla, the two anti-amyloid monoclonal antibodies approved in the United States for Alzheimer’s, are designed to help clear different forms of beta-amyloid from the brain. Clinical trials found that both drugs modestly slowed cognitive and functional decline in people with early Alzheimer’s, but neither reverses lost memory or cures the disease, and their benefits must be weighed against treatment risks.

Monoclonal antibodies are laboratory-made proteins engineered to bind to a specific target. In Alzheimer’s, Leqembi, whose generic name is lecanemab, binds to amyloid plaques and smaller beta-amyloid groupings called protofibrils. Kisunla, or donanemab, primarily targets a modified form of beta-amyloid found in established plaques. Once attached, the antibodies help the immune system clear amyloid from the brain.

The drugs act on a biological feature associated with Alzheimer’s, rather than directly replacing lost abilities or simply addressing symptoms. In phase 3 trials, both substantially reduced brain amyloid and slowed decline on measures of cognition and daily function. In Leqembi’s trial, participants declined about 27% more slowly over 18 months than people given a placebo. In Kisunla’s trial, participants across the overall study population had a 37% lower risk of progressing to the next clinical stage over 76 weeks than placebo recipients.

Those figures come from separate trials with different designs and time periods; they are not a head-to-head comparison. The source report says the drugs are intended for people in the earliest symptomatic stages of Alzheimer’s. Neither can restore memory already lost, and the size of the measured slowing does not by itself settle how much patients may notice in daily life.

What Slower Decline May Mean

The drugs offer a treatment option that targets a disease-associated process, but the expected effect is a slowing of decline, not recovery. For patients and families, that distinction matters when weighing treatment against its demands and risks. The evidence does not promise that a person will remain stable or experience a noticeable change in everyday activities.

Safety is part of that decision. The report says anti-amyloid antibodies increase the risk of brain swelling and bleeding. A review cited by the report also questioned whether average benefits across the antibody class amount to a clinically meaningful difference, while some Alzheimer’s specialists disputed its conclusions. The disagreement reflects a live question: how trial-scale changes should be interpreted for individual patients, and whether removing amyloid reliably corresponds to greater clinical benefit.

Two Drugs, Different Amyloid Targets

Beta-amyloid can gather into aggregates and plaques between brain cells. Plaques are a hallmark associated with Alzheimer’s, but scientists are still studying how different forms of amyloid contribute to cognitive decline. The antibodies’ distinct targets are one reason their trial results should not be treated as a direct comparison of which drug works better.

Leqembi received U.S. approval in July 2023, followed by Kisunla about a year later. Both are described in the source report as disease-modifying treatments because they act on underlying disease biology and alter the course measured in trials. That label does not mean they stop Alzheimer’s or eliminate its symptoms. Researchers are also investigating antibodies directed at other targets, including proteins on immune cells in the brain.

Evidence outside trials is developing. An Eisai-funded study of 177 people treated with Leqembi for one year reported that 77% had not advanced to the next disease stage and 7% had moved from early Alzheimer’s to mild cognitive impairment. The study lacked a placebo group, so it cannot establish how much of that stability was caused by the drug. Short follow-up also makes longer-term effects hard to assess.

“Existing approved drugs offer some benefit for some patients, but there remains a high unmet need for more effective treatments.”

— Edo Richard, professor of neurology at Radboud University Medical Centre and senior author of the Cochrane review, in a press release

How Much Benefit Patients Notice

It remains unsettled how closely amyloid removal corresponds to slower cognitive decline. The report notes that newer research suggests clearing more amyloid does not necessarily produce more slowing. Researchers also disagree about whether the average effects reported in trials are clinically meaningful for patients’ daily lives.

Long-term real-world impact is not yet clear. Alzheimer’s can progress slowly, while the drugs’ effects are modest, making a year or two of observation difficult to interpret. The cited Leqembi study had no placebo group, and its results cannot show what would have happened to the same participants without treatment. The source report does not provide enough detail to determine individual eligibility, treatment monitoring schedules, or how risks compare for particular patients.

Longer Follow-Up and Patient Selection

Researchers will need longer follow-up and stronger real-world comparisons to clarify how durable the treatment effects are and how they translate into everyday functioning. Continued study is also needed to understand the link between amyloid reduction and clinical outcomes, and to identify which patients are most likely to benefit relative to the risks.

For now, the evidence described supports a measured conclusion: Leqembi and Kisunla can slow decline modestly in early Alzheimer’s, but they are not cures, and their benefit for an individual cannot be inferred from trial averages alone. Decisions about treatment require consideration of a person’s stage of disease, potential risks, and clinical circumstances with qualified health professionals.

Key Questions

How do Leqembi and Kisunla work?

Both are laboratory-made antibodies that bind to beta-amyloid and help the immune system clear it from the brain. Leqembi targets plaques and smaller aggregates called protofibrils; Kisunla primarily targets a modified form found in established plaques.

Do the drugs cure Alzheimer’s or restore lost memory?

No. The source report says neither drug cures Alzheimer’s or restores memory that has already been lost. Trial results indicate that they can modestly slow cognitive and functional decline in people with early disease.

How much did the drugs slow decline in trials?

In separate phase 3 trials, Leqembi was associated with about 27% slower decline over 18 months than placebo. Kisunla was associated with a 37% lower risk of progressing to the next clinical stage over 76 weeks across its overall study population. These are different trial measures and do not establish which drug is more effective.

What risks are reported?

The source report says anti-amyloid antibodies increase the risk of brain swelling and bleeding. It does not give individual risk estimates here. Patients should discuss treatment risks and suitability with a qualified health professional.

Who were the drugs studied for?

The report says Leqembi and Kisunla were studied and approved for people in the earliest symptomatic stages of Alzheimer’s. Individual eligibility depends on clinical circumstances; the supplied information does not specify all eligibility criteria.

Source: rss