The New Alzheimer's Drugs (Leqembi, Kisunla): What They Do | Philadelphia

TL;DR30-second take

Lecanemab (Leqembi) and donanemab (Kisunla) are the first drugs shown to change the course of Alzheimer's disease. They are antibodies, given by infusion, that clear amyloid, the protein that builds up in the Alzheimer's brain. In large trials they slowed the decline of memory and function by roughly a quarter to a third compared with placebo, a genuine milestone, though the difference is modest and its everyday noticeability is debated. They carry a notable risk called ARIA, brain swelling or small bleeds seen on MRI, and they require regular scans, amyloid testing, and gene testing. They are only for early Alzheimer's with confirmed amyloid, they slow the disease rather than stopping or reversing it, and they are not a cure.

TL;DR: Lecanemab (Leqembi) and donanemab (Kisunla) are the first drugs proven to change the underlying course of Alzheimer's disease, rather than only easing symptoms. They are antibodies, given by infusion, that clear amyloid, the protein that clumps in the Alzheimer's brain. In large trials they slowed the decline of memory and daily function by roughly a quarter to a third versus placebo over 18 months, a genuine scientific milestone. But the benefit is modest: the gap is small, and experts debate how much a patient or family would notice it. The drugs carry a serious risk called ARIA, brain swelling or small bleeds usually caught on MRI but occasionally dangerous, and they demand regular scans, amyloid confirmation, and gene testing. They are only for early Alzheimer's with confirmed amyloid, they slow the disease rather than stopping or reversing it, and they are not a cure.

What are the new Alzheimer's drugs?

For decades, Alzheimer's had no treatment that touched the disease itself; the available drugs only softened symptoms for a while. That changed with lecanemab and donanemab, two antibodies that target amyloid, a sticky protein that accumulates into plaques in the brains of people with Alzheimer's. Given by infusion, these drugs bind amyloid and prompt the immune system to clear it, and in doing so they modestly slow the disease's progression. That makes them the first disease-modifying treatments for Alzheimer's.

Lecanemab, sold as Leqembi, received full FDA approval in 2023 and is given as an infusion every 2 weeks. Donanemab, sold as Kisunla, was approved in 2024 and is given monthly. Both are for people in the early stages of Alzheimer's, and both work the same basic way, by removing amyloid, though they differ in details covered below. An earlier drug in this class, aducanumab, was withdrawn from the market, leaving these two as the approved options.

How well do they work?

This is where care in framing matters most, because the answer is mixed: a clear scientific success and a modest clinical effect at the same time.

In its pivotal trial, CLARITY-AD, lecanemab slowed the decline of memory and daily function by about 27% over 18 months compared with placebo.¹ Donanemab, in its trial TRAILBLAZER-ALZ 2, slowed decline by roughly 22% to 36%, with the larger figure in patients whose disease was caught earliest.² Both cleared most of the amyloid from the brain, confirming that the drugs do what they are designed to do.

The catch is in the size of that slowing. A 27% relative slowing sounds substantial, but the underlying difference was small: on the main 18-point rating scale, the lecanemab group declined by about 0.45 points less than placebo over 18 months. Both groups still got worse; the treated group just got worse a little more slowly. Put another way, donanemab bought patients roughly 5 additional months before reaching the same level of decline. Whether a gap that size is something a patient or family would notice is a genuine and unsettled debate among specialists. The fair summary is that these drugs do slow Alzheimer's, and that the amount they slow it is modest.

The main risk: ARIA

The defining safety concern with these drugs is a side effect called ARIA, short for amyloid-related imaging abnormalities. As the drugs strip amyloid out of the brain, including amyloid in blood vessel walls, they can cause two problems visible on an MRI scan: swelling of brain tissue, and small spots of bleeding.

Most ARIA causes no symptoms and is found only because patients get regular MRI scans while on treatment; it usually appears in the first few months, is mild, and resolves. But it is not always benign. A minority of people develop symptoms like headache, confusion, or dizziness, and rarely, ARIA can be serious or even fatal, particularly in people on blood thinners or with certain genetic risk. ARIA is the reason these drugs require a schedule of monitoring MRIs and careful patient selection, and it is why they are prescribed through specialists rather than routinely. With lecanemab, some form of ARIA appeared in about one in five people in the trial; with donanemab it was somewhat higher, though a newer, slower dosing schedule approved in 2025 has lowered that rate.

Who can take them, and the role of the APOE4 gene

Eligibility is narrow, and getting it right is central to using these drugs safely.

They are approved only for people with early Alzheimer's, meaning mild cognitive impairment or mild dementia caused by Alzheimer's, and only when the presence of amyloid has been confirmed, historically by a PET scan or spinal fluid test and now increasingly by a newly cleared blood test. They are not approved for moderate or advanced Alzheimer's, for memory loss from other causes, or for preventing Alzheimer's in people without symptoms. Someone with significant memory decline may assume these drugs can help, but if the disease is past the early stage, or if it is not Alzheimer's, they are not an option.

Before starting, patients are tested for a gene called APOE4. People who carry two copies of this gene, one from each parent, face a substantially higher risk of ARIA, including its more serious forms. This does not automatically rule them out, but it changes the conversation: the higher risk has to be weighed carefully against the modest benefit, with clear informed consent. Gene testing before treatment has become a standard part of deciding whether these drugs make sense for a given person.

The practical reality, and the cost

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Beyond the biology, these are demanding treatments to undergo. A typical course involves confirming amyloid with a scan or test, genetic testing, infusions every 2 or 4 weeks at an infusion center, and a series of MRI scans to watch for ARIA, above all in the first months. The drugs are expensive, with lecanemab priced around $26,500 a year, and the scans, testing, and infusion visits add substantial cost and time on top of that.

The field is moving quickly, and some of that burden is easing. In 2025 an at-home subcutaneous injection version of lecanemab was approved for maintenance dosing, reducing infusion-center visits. Donanemab can be stopped once its scans show the amyloid has been cleared, which can shorten the course. And the arrival of a blood test for amyloid, cleared by the FDA in 2025, is making the diagnostic step simpler. These are meaningful improvements over the original picture, even as the core trade-off of modest benefit against notable risk and cost remains.

The bottom line, and where prevention fits

So how should you think about these drugs? As a genuine milestone that is also a modest treatment. They prove, for the first time, that removing amyloid can slow Alzheimer's, which is a scientific achievement and a foundation for better drugs to come. For a person with early, amyloid-confirmed Alzheimer's who understands the trade-offs, wants to act, and has low bleeding risk, they are a reasonable option that may buy some time. For many others, the modest benefit, the ARIA risk, the monitoring, and the cost will tilt the decision the other way. It is a deeply personal choice, made with a specialist, and there is no single right answer.

What these drugs do not do is prevent Alzheimer's, and that keeps the focus on the levers that lower risk before symptoms begin. Trials testing whether clearing amyloid in people without symptoms can prevent the disease are underway, but they have not reported. In the meantime, the proven prevention levers remain the ones to act on: blood pressure and blood sugar control, physical activity, hearing, sleep, social connection, and, as an unusually easy addition, the shingles vaccine, which is linked to lower dementia risk. Our cognitive health guide covers that fuller picture.

Guidance from the Clinic

"When a family asks me about Leqembi or Kisunla, I try to give them the whole truth rather than the headline in either direction. These are a true achievement, the first drugs that touch the disease instead of just the symptoms, and I do not want to dismiss that. But I am equally careful not to oversell them. They slow the decline modestly, they do not stop or reverse it, they carry a brain-swelling risk that demands MRI monitoring, and they are a major commitment of time and money. For the right person, caught early, with eyes open, they can be worth it. For many, the balance falls the other way. What I never want is for the excitement about these drugs to pull attention away from the prevention that helps many more people: protecting the heart, the metabolism, the hearing, and the sleep, long before any of this is on the table."

Key Takeaways

Lecanemab (Leqembi) and donanemab (Kisunla) are the first disease-modifying Alzheimer's drugs, antibodies given by infusion that clear amyloid and modestly slow the disease.
In trials they slowed decline by roughly a quarter to a third over 18 months, a scientific milestone, but the absolute difference is small and its everyday noticeability is debated.
Their defining risk is ARIA, brain swelling or small bleeds seen on MRI, usually without symptoms but occasionally serious, which requires regular monitoring scans.
They are only for early, amyloid-confirmed Alzheimer's; they do not apply to advanced dementia, other causes of memory loss, or prevention; APOE4 gene testing helps gauge the risk, and two copies raise it substantially.
They slow the disease rather than curing it, they are costly and demanding, and they do not replace prevention, which remains the larger lever for the brain.

The Shingles Vaccine and Dementia - a prevention lever linked to lower dementia risk
Cognitive Health and Dementia Prevention - the fuller picture of protecting your brain
Hearing Loss and Dementia Prevention - another modifiable dementia-risk lever
Family History and a Prevention Plan - building prevention around your inherited risk
The Four Horsemen - where dementia fits the longevity picture
Should You Test for APOE4? - the risk gene that shapes both your odds and these drugs' safety
The Alzheimer's Blood Test (p-tau217): What It Means - the blood test that confirms amyloid before these drugs, and who should get it

Scientific References

van Dyck CH, Swanson CJ, Aisen P, et al. "Lecanemab in Early Alzheimer's Disease." New England Journal of Medicine. 2023;388(1):9-21.
Sims JR, Zimmer JA, Evans CD, et al. "Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial." JAMA. 2023;330(6):512-527.

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Frequently Asked Questions

Common Questions

They are the first drugs proven to change the course of Alzheimer's disease, rather than only treating symptoms. Both are antibodies, given by infusion, that clear amyloid, the protein that builds up in the Alzheimer's brain. Lecanemab is given every 2 weeks and donanemab monthly. Both are approved only for early Alzheimer's with confirmed amyloid, and both slow the disease modestly rather than curing it.

In their trials, they slowed the decline of memory and function by roughly a quarter to a third over 18 months compared with placebo. That is a genuine effect, but the size of the difference is small: patients still declined, just more slowly, gaining something like a few extra months before reaching the same stage. Whether that is enough to notice is debated among experts. They are a scientific milestone with a modest clinical benefit.

ARIA, or amyloid-related imaging abnormalities, is the main side effect of these drugs: swelling or small bleeds in the brain, seen on MRI, that happen as amyloid is cleared. Most cases cause no symptoms and are found only through the routine MRI scans required during treatment, and they usually resolve. But some cases cause symptoms, and rarely ARIA can be serious or fatal, more so in people on blood thinners or with two copies of the APOE4 gene. It is the reason these drugs require careful monitoring and specialist oversight.

Only people with early Alzheimer's, meaning mild cognitive impairment or mild dementia due to Alzheimer's, whose amyloid has been confirmed by a PET scan, spinal fluid test, or the newer blood test. They are not approved for moderate or advanced dementia, for memory loss from other causes, or for people without symptoms. Doctors also test for the APOE4 gene beforehand, since carrying two copies raises the risk of side effects.

Lecanemab is priced around $26,500 a year, and donanemab is comparable, though its ability to be stopped once amyloid is cleared can lower the total. On top of the drug, there are costs for amyloid confirmation, gene testing, infusions, and the series of MRI scans to monitor for ARIA, which together add substantial expense and time. Coverage varies, and the full burden is a significant part of the decision.

Deep-Dive Questions

Because a percentage can make a small absolute difference sound large. The trials measured decline on rating scales, and the treated groups declined by a small margin less than the placebo groups, for example about 0.45 points less on an 18-point scale over 18 months. Expressed as a share of the placebo group's decline, that becomes 27%, which sounds impressive, but the underlying gap is narrow, and both groups clearly worsened. This is why specialists debate whether the benefit is large enough for patients and families to perceive in daily life. The drugs work in a measurable, statistical sense; the question is how much that translates into a difference someone would feel.

Because amyloid is part of the story rather than the whole story. The amyloid hypothesis holds that amyloid plaques are a key driver of Alzheimer's, and these drugs, by clearing amyloid and slowing decline, support that idea. But Alzheimer's also involves another protein called tau, along with inflammation, vascular damage, and other processes, and removing amyloid does not undo those. That is likely why clearing most of the amyloid only slows the disease modestly rather than halting it. It suggests amyloid is one lever among several, and that future treatments may need to target more than one at once.

It depends on symptoms and goals, and it is a decision to make with a doctor. For someone with early memory symptoms, confirming whether Alzheimer's and amyloid are present can guide whether these drugs are an option, so testing has a clear purpose. For someone without symptoms who is simply worried, the calculus is different: amyloid and APOE4 testing can reveal risk, but since the drugs are not approved for prevention and carry their own risks, a positive result may bring anxiety without a clear action. Some people still want to know, to plan and to focus on prevention. It is a personal choice best made with counseling about what the results would and would not change.

It sits downstream of prevention, which is where most of the leverage still lies. These drugs treat Alzheimer's once it has begun and been diagnosed; they do nothing for the years before, when risk is being built or lowered. The proven ways to lower dementia risk act in that earlier window: controlling blood pressure, blood sugar, and cholesterol, staying physically active, treating hearing loss, sleeping well, staying socially connected, and getting the shingles vaccine, which is linked to lower dementia rates. For most people, those levers will do more for their brain over a lifetime than any amyloid drug, which is why prevention remains the foundation even in the era of disease-modifying treatment.

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