Understanding Leqembi and Kisunla: A Guide to New Alzheimer's Treatments

These new therapies represent a paradigm shift—they are the first treatments that actually target the underlying disease process rather than just managing symptoms.

But they also raise important questions:

• Is modest slowing of decline worth the risks and costs?

• How do we ensure access for those who could benefit?

• What does "success" look like in Alzheimer's treatment?

These are the conversations most family caregivers will be having. By understanding the science behind these drugs—how they work, who they're for, and what the evidence shows—they'll be better equipped to have those conversations with their doctors and their families.

Disclaimer: This article is for educational purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider about treatment decisions.

A "Cellular Custodial Crew": A Framework for Understanding

Before we talk about the drugs themselves, let's set up a mental picture we can carry through the rest of this article.

Imagine your brain is a grand, historic library. For decades, the shelves have been accumulating a sticky, unwanted substance—amyloid plaques. Think of these like wads of old gum that have been pressed into the carpet and between the bookshelves. They're not supposed to be there, and over time, they make it harder for the librarians (your brain cells) to do their jobs.

Your brain has its own custodial staff—special immune cells called microglia. These cells are the library's cleaning crew. They patrol the aisles, and they can see the gum (the plaques). But for reasons scientists are still working to understand, the cleaning crew in an Alzheimer's brain doesn't grab the gum and throw it away.

They just look at it and keep walking.

Leqembi and Kisunla are not gum dissolvers. They are high-tech "work orders" that finally tell the custodial crew, "This gum? Right here? Take it out."

Here is how that work order is written and delivered.

Understanding Leqembi and Kisunla: A Guide to New Alzheimer's Treatments

If you or someone you love is navigating early Alzheimer's disease, you may have heard about two new treatments generating both hope and questions: Leqembi (lecanemab) and Kisunla (donanemab) . These are the first therapies that actually target the underlying biology of the disease rather than just managing symptoms.

Let's walk through what they are, who they're for, how they work, and what the evidence shows—in plain language.

What Are These Medicines?

Both Leqembi and Kisunla belong to a class of drugs called monoclonal antibodies. Think of them as specially designed "search-and-destroy" proteins. They are custom-built in a lab to find and attach to one specific thing in the body: amyloid plaques in the brain.

Amyloid plaques are sticky protein clumps that build up between nerve cells in Alzheimer's disease. For decades, scientists have known these plaques are a hallmark of the disease, but until recently, we didn't have drugs that could effectively clear them.

• Leqembi (lecanemab-irmb) was first approved by the FDA in July 2023 for early Alzheimer's disease.

• Kisunla (donanemab-azbt) received FDA approval in July 2024

Who Qualifies for These Treatments?

This is one of the most important things to understand: these are not for everyone with dementia. They are specifically for people in the early stages of Alzheimer's disease—which means:

• Mild cognitive impairment (MCI) due to Alzheimer's

• Mild dementia due to Alzheimer's

Before treatment can begin, doctors must confirm two things:

1. You have Alzheimer's disease, not another form of dementia. This is done through biomarker testing—either a PET scan that shows amyloid plaques in the brain or a spinal fluid (CSF) test.

2. You are in the early stage of the disease, meaning your symptoms are still mild.

Doctors will also run blood tests and genetic testing (for the APOE gene) because certain genetic profiles affect both the risk of the disease and the likelihood of side effects.

Key takeaway: These drugs treat Alzheimer's disease by targeting its defining feature—amyloid plaques. They do not treat other types of dementia like vascular dementia or frontotemporal dementia.

Is It Covered by Medicare and Medicaid?

Yes, but with conditions.

Medicare Part B covers both Leqembi and Kisunla for eligible patients who:

• Meet the prescribing criteria (early-stage Alzheimer's with confirmed amyloid pathology)

• Are enrolled in a qualifying patient registry or study

However, coverage isn't automatic. Here's what that means in practical terms:

• Traditional Medicare typically pays 80% of the cost. You may be responsible for the remaining 20% plus your yearly deductible (which is $283 in 2026).

• A Medigap (Medicare Supplement) plan can help cover your share of costs.

• Medicare Advantage plans vary—you'll need to check your specific plan benefits.

Medicaid coverage is also available in some states. For example, Kisunla became a benefit of Medicaid and CHIP in Texas starting January 1, 2025, though prior authorization is required.

Commercial insurance is a mixed picture. Some private insurers cover these drugs, while others have denied coverage. It's essential to call your insurance provider directly to understand your specific coverage.

Cost considerations:

• Leqembi's list price is about $27,439 per year** for a patient weighing 165 pounds receiving IV treatment twice monthly. A newer at-home injection formulation (Leqembi Iqlik) has a market price of **$19,500 for a year's treatment.

• Kisunla's manufacturer has announced a yearly price of $32,000.

Most patients don't pay the full list price due to insurance coverage and manufacturer assistance programs.

How Long Are Patients Expected to Be on Treatment?

This is where Leqembi and Kisunla differ significantly.

Leqembi: Ongoing Treatment

Leqembi is designed as a long-term therapy:

• Initial phase: IV infusion once every two weeks for 18 months.

• After 18 months: Patients have two options for maintenance:

  1. Continue IV infusions once every four weeks

  2. Switch to a weekly at-home injection (Leqembi Iqlik) using an autoinjector

Why continue treatment? Because Alzheimer's is a progressive disease. Even after plaques are cleared, the underlying neurotoxic process continues. Data shows that stopping treatment leads to a gradual return of amyloid in the brain, while continuing treatment helps maintain the benefits.

Kisunla: Limited-Duration Treatment

Kisunla takes a different approach—it's designed as a finite course of therapy:

• Monthly IV infusion, with each session lasting about 30 minutes.

• Treatment continues until amyloid plaques are reduced to minimal levels, as confirmed by PET scans.

• Some people may complete treatment in as little as 6–18 months.

• The maximum treatment duration is 18 months.

Once plaques are cleared, treatment stops. The manufacturer reports that after completing treatment, amyloid plaque reaccumulation remains slow.

The key difference: Leqembi is like ongoing maintenance—you keep taking it to keep the disease in check. Kisunla is more like a course of treatment—you take it until the plaques are cleared, then you stop.

How Do These Drugs Actually Work? (The "Under the Hood" Explanation)

Now let's get to the heart of your question: the mechanism of action. I'll keep this as accessible as possible.

The Problem: A Brain Full of "Gum"

Imagine your brain is a beautifully organized library. Over decades, a sticky substance—amyloid plaques—has been accumulating between the shelves. Think of these like wads of gum pressed into the carpet. They don't belong there, and over time, they make it harder for the librarians (your brain cells) to do their jobs.

Your brain has its own custodial staff—special immune cells called microglia. These cells are the library's cleaning crew. They can see the gum, but for reasons scientists are still trying to understand, they don't pick it up. They just walk past it.

The Solution: A "Work Order" for the Cleaning Crew

Both Leqembi and Kisunla are monoclonal antibodies—lab-made proteins that act like high-tech work orders. They don't clean up the plaques themselves. Instead, they tag the plaques and finally tell the cleaning crew: "This gum? Right here? Take it out."

Here's how it works, step by step:

Step 1: The Searchlight
Each antibody has a business end—a part that scans the brain, finds amyloid plaques, and locks onto them. This is like the part of the work order that says, "This is the gum that needs to be removed."

Step 2: The Handle
The other end of the antibody is a handle that the microglia (the cleaning crew) can grab onto. When the microglia grab that handle, they are activated. They shift into a different mode of operation.

Step 3: Cleanup Mode
Once activated, the microglia engulf the tagged plaque and break it down. Scientists call this phagocytosis—literally, "cell eating." The plaques are cleared from the brain.

The Difference Between Leqembi and Kisunla

Both drugs use the same basic system. The difference is in what they target:

• Leqembi targets protofibrils—smaller, highly toxic clumps of amyloid that form before they become full-blown plaques. Think of this as finding the gum when it's still fresh and sticky. Recent research suggests Leqembi works in two ways: it clears both these toxic protofibrils and the mature plaques.

• Kisunla targets a specific, modified form of amyloid called N3pG that is found inside already-formed, mature plaques. Think of this as coming in with a work order specifically for the old, hardened gum that's been there for years.

Both get the job done. They just operate at different stages of the mess.

The "Foreign Substance" Question

You might wonder: if these are lab-made proteins, doesn't the body reject them as foreign?

This is where the science gets really clever. Early therapeutic antibodies were made entirely from mouse proteins. When injected into humans, the immune system recognized them as foreign and attacked—creating what's called a human anti-mouse antibody (HAMA) response.

Modern antibodies like Leqembi and Kisunla are humanized—meaning scientists have replaced most of the mouse parts with human antibody sequences. The drug looks mostly like a "self" protein to your immune system, so it's less likely to be rejected. This is why these treatments can be given repeatedly without triggering a major immune attack.

Do Data Show They Actually Work?

This is the question that matters most. The short answer is: yes, they slow cognitive decline—but the effect is modest, and it's not a cure.

Leqembi (Lecanemab): The Evidence

The pivotal study was called Clarity AD, an 18-month Phase 3 trial.

Primary results at 18 months:

• Patients on Leqembi showed 27% less cognitive decline compared to placebo, measured on a scale called CDR-SB (Clinical Dementia Rating-Sum of Boxes).

Longer-term data (up to 4 years):

• At 36 months: 0.95-point reduction in cognitive decline compared to a matched untreated group.

• At 48 months: 1.75-point reduction in cognitive decline compared to the expected decline.

Perhaps most encouraging: among patients with low tau (a marker of less advanced disease), 69% showed no decline on the CDR-SB scale, and 56% actually showed improvement.

Recent data presented at the CTAD 2025 conference suggests that with continued treatment, Leqembi may have the potential to delay disease progression by up to 8.3 years. While this is a model-based estimate, it's generating significant excitement in the field.

Kisunla (Donanemab): The Evidence

The pivotal study was called TRAILBLAZER-ALZ 2, a 76-week Phase 3 trial.

Primary results:

• In the overall patient population: 22% slowing of clinical decline compared to placebo.

• In patients with less advanced disease (low-to-medium tau): 35% slowing of decline.

• Patients treated with Kisunla had up to a 39% lower risk of progressing to the next clinical stage of disease.

Amyloid clearance:

• 61% reduction in amyloid plaques at 6 months

• 80% reduction at 12 months

• 84% reduction at 18 months

• More than 75% of participants reached amyloid clearance within 76 weeks

Longer-term data (3 years):

• Kisunla reduced cognitive decline by -0.6 at 18 months and -1.2 at 36 months on the CDR-SB scale.

• Earlier initiation of treatment reduced the risk of progression to the next stage by 27% compared to delayed initiation.

Putting the Numbers in Perspective

A 27% or 35% slowing of decline might not sound dramatic. But here's what it means in real life: a difference of 0.5 to 1 point on the CDR score represents the difference between slight impairment and loss of independence—such as the ability to be left alone, remember recent events, or participate in daily activities.

These drugs don't reverse Alzheimer's. But they can give people more time—more time with their families, more time to manage their affairs, more time to be themselves.

A Note About Safety

Both drugs carry a boxed warning for ARIA (Amyloid-Related Imaging Abnormalities) —which means swelling or small bleeding in the brain. This is why patients need regular MRI monitoring before and during treatment.

• For Leqembi: ARIA is most common during the first six months of treatment.

• For Kisunla: A new, modified dosing schedule approved in July 2025 has been shown to reduce the risk of ARIA-E (swelling) by 41% at 24 weeks compared to the original dosing regimen, while maintaining the same level of amyloid reduction.

These are serious considerations that patients and their doctors must weigh carefully against the potential benefits.

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