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7 Things to Know About New Alzheimer’s Drug Kisunla

By | July 15th, 2024

Expert-backed information about Eli Lilly's new Alzheimer's disease treatment Kisunla, from how it works, to how well it works, and more.

A new drug for Alzheimer’s was just this month approved by the FDA for use in the United States, in people in the earliest stages of the disease. It’s a monoclonal antibody called Kisunla, by drugmaker Eli Lilly, and it’s part of a new generation of Alzheimer’s drugs designed not only to ease symptoms, but to actually treat the disease pathology itself as it spreads through the brain. Over the past four years, clinics around the world have been conducting extensive phase 2 and then phase 3 clinical trials of Kisunla under its generic name, donanemab. Here are seven key things to know about Kisunla: how it works, how well it works, and more.

1. Kisunla is part of a new category of Alzheimer’s drugs called monoclonal antibody (mab) anti-amyloid drugs.

Monoclonal antibody drugs (we call them “mab” drugs for short) are in use for the treatment of many diseases, including cancer. These therapies are designed to bind to a single antigen — for example, a cancer cell protein — and can be used alone or to deliver other substances to the cells they’re looking for.

Some mab drugs are considered immunotherapies, because they help the immune system recognize and destroy certain target cells.

In the landscape of Alzheimer’s treatment, scientists have harnessed this technology to seek out beta-amyloid protein cells: Alzheimer’s best-known and longest-targeted (though little understood) biomarker. Amyloid proteins build up in the brains of people with Alzheimer’s, causing clumps that interrupt the work of brain cells, and eventually cause cell death. Some scientists think this clumping protein process is what causes Alzheimer’s disease to progress. Whether or not it’s the cause, it is certainly one of the disease’s most widely shared pathological traits.

These Alzheimer’s anti-amyloid mab drugs are the disease’s first disease-modifying drugs, because they don’t just put a band-aid on the drug’s symptoms: They work at a pathology level to prevent the buildup of these amyloid plaques in the brain. Leqembi attaches to beta-amyloid before it forms plaques and Kisunla attach to beta-amyloid once it has formed the plaque.

The latter approach was also the approach of Aduhelm (aducanumab), the world’s first mab drug, which was conditionally approved by the FDA in 2021 but which underperformed and was discontinued by the drugmaker in 2024.

2. Kisunla is for people in the earliest stages of Alzheimer’s, when symptoms are still mild.

Like its predecessor -mab drugs for Alzheimer’s, Kisunla was approved specifically for people in the earliest stages of Alzheimer’s, before symptoms are deeply disruptive of everyday life. In the phase 3 trials, the approximately 1,736 participants were split into groups based on how much of another biomarker protein, tau, was tangled up in their brains. Participants in the control group who had medium levels of tau in their brain benefited most, while patients with high levels of tau overall benefitted least.

On the label, the drug is described as “an amyloid-targeting treatment for people with mild cognitive impairment (MCI) as well as people with mild dementia stage of early symptomatic Alzheimer’s disease, with confirmed amyloid pathology.”

Not all MCI will progress to Alzheimer’s or another dementia, and some cases have other underlying causes that can be treated. But if amyloid is present, there is a higher chance the MCI is the symptomatic manifestation of the earliest phase of Alzheimer’s.

The earlier in their course of disease that the participants received the drug, the more improvement they experienced in the trials — a case, experts say, for the need for more accurate, more accessible diagnostics that can catch Alzheimer’s earlier, ideally before symptoms even appear.

3. Kisunla isn’t designed to cure Alzheimer’s disease.

Kisunla might help slow the progression of Alzheimer’s disease, but it’s not a cure.  The Phase 3 trial found the drug did not stop cognitive decline, but appeared to slow the progress of the disease in the early stages, and lowered the risk of progressing to the next stage of Alzheimer’s: Over the course of a year, one in six patients who received the drug progressed to the next stage of the disease compared to one in four in the placebo group.

While Kinsunla did appear to reduce cognitive symptoms in trial participants, it had showed only a fraction-of-a-point benefit (on two different scales) for the control group (people who were taking the drug) over the placebo group (people who thought they were taking the drug, but weren’t).

Both groups saw their symptoms worsen progress over the course of 18 months, but those taking the drug declined a little bit slower than the placebo group. Based on the trial data, Eli Lilly estimates that this drug may delay progression on average of about 7.5 months, as compared to the placebo.

For some patients, that fraction-of-a-point difference is tangible: In one account, from an FDA advisory committee hearing about Kisunla in June 2024, in the lead-up to its approval, one spouse of a person with Alzheimer’s, Sandra Carlino, spoke on behalf of her husband George who had participated in the Kisunla (donanemab) trial: “Our experience in this trial has been life-changing,” she said. “We understand that his disease may never be cured, but his progression has slowed down immensely that to the point of a casual observer or acquaintance they would not know he has this condition.”

How Do Alzheimer’s Clinical Trials Work? And Other FAQs

 

4. You’ll need to visit a specialty infusion center at least once per month to receive Kisunla.

Easier and more accessible drug formats for a new generation of disease-modifying Alzheimer’s treatments are in development. (For example, a pill to treat Alzheimer’s is currently in trials.) But for now, the mab drugs on the market are administered by IV infusion. (The earliest, Aduhelm, before it was taken off the market, was infused via spinal infusion — so IV is a step in the right direction.)

Currently, Leqembi and Kisunla are both infused intravenously. According to the label, Kisunla is administered intravenously every four weeks, at a dose of 700 mg for the first three doses and 1400 mg thereafter. (Side effects related to infusion are noted as a possibility.)

For some patients, it may not be so easy to access one of these specialty centers.

Alzheimer’s Rates Are Highest In These Counties—But No Leqembi Access

5. ApoE4 carriers should be aware of higher risks when taking Kisunla and other Alzheimer’s mabs.

The Alzheimer’s risk gene variant ApoE4 did not affect how well the drug worked. But, it did seem to influence a person’s vulnerability to side effects. This is similar to what has been seen in earlier mab trials.

Like most drugs, this class of Alzheimer’s drugs comes with a risk of side effects, including one known as ARIA, amyloid related imaging abnormalities. There are two types of ARIA, brain swelling or tiny brain bleeds. Most of the time, this side effect doesn’t lead to any symptoms, meaning there are no outward signs of it at all.

In rare cases, ARIA can be serious. During the drug trials for Leqembi (which was referred to during trials by its generic name, lecanemab), at least one of the three patients who died had signs of ARIA in their brains. The participants who took Kisunla (donanemab) had a slightly higher mortality rate: 2 percent, compared with 1.7 percent in the placebo group. Three active donanemab trial participants died after developing ARIA.

The risks are significantly higher for carriers of a genetic variant called ApoE4.

“The prevailing thought at this moment is that amyloid deposits in the blood vessels called cerebral amyloid angiopathy and APOE4 carriers tend to have more cerebral amyloid angiopathy,” Dr. Marwan Sabbagh, a neurologist at the Barrow Institute, told Being Patient in a conversation about ARIA and Kisunla’s predecessor mab drug, Leqembi, which is also on the market. “And that because you have more amyloid in your blood vessels, when you bind those blood vessels with these monoclonal antibodies, that, or at least the amyloid, you make them leaky. And that’s what’s causing the ARIA.”

According to Sabbagh, for people who do not carry APOE4, the risk of ARIA while on Leqembi is about 5 percent. If you have a single copy of the gene, that risk rises to 15 percent, two copies, 33 percent.

Neurologist Daniel Gibbs, the author of A Tattoo on My Brain, spent 25 years caring for Alzheimer’s patients before he was diagnosed with Alzheimer’s disease himself. He’s a carrier of two copies of ApoE4 and experienced ARIA during a clinical trial for the now discontinued Aduhelm.

6. When Kisunla has done its job, you can stop taking it.

According to the label, when Kinsunla has cleared the plaque from the brain, a patient can stop taking it. This isn’t the case with Leqembi as of now: There is no label recommendation on Leqembi to stop taking the drug at any point. In the phase 3 trials, half participants taking Kinsunla went off the drug after a year after amyloid plaques were cleared from their brain. More widespread and longer-term use will mean more data to understand the long-term effects of the drug.

7. Insurance coverage for Kisunla should be less of a headache for patients than previous mab drugs for Alzheimer’s.

There was a time as recently as a year ago that Medicare declared it wouldn’t cover this new class of drugs for Alzheimer’s. Luckily for patients, that soon changed, with the full FDA approval of Kisunla’s predecessor, Leqemebi. Medicare and Medicaid will cover the cost of the drug, in line with its coverage policy as of June 2023. Those who would pay out of pocket will have some big bills to field: A year on the drug would cost $32,000.

According to a press release from the drugmaker, the total cost of Kisunla for a patient depends on how long a patient’s course of treatment lasts, and this can vary person to person. Again, in the trials, about half of patients stayed on the drug for one year. Eli Lilly is fielding patient questions directly about coverage and coordination.

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6 thoughts on “7 Things to Know About New Alzheimer’s Drug Kisunla

  1. Is it also true that being on blood thinners increases the risk of ARIA, as it does with the other -mab drugs?

    1. Hi Leslie, thank you for reaching out. Anticoagulants may increase the risk of brain bleeds, so some doctors might not prescribe people on anticoagulants anti-amyloid drugs and others might be extra cautious about it. We hope that helps!

  2. I was in the aduhelm trial and received 34 monthly infusions that were given intravenously not via spinal infusions.

  3. Do you have any information as to whether it is recommended that patients who have been taking Leqembi for a long time should switch to Donanamab. My wife has been taking Leqembi for over a year now with no end in sight, it seems.

    1. Hi Robert, thank you for reaching out. As of now, we are still unsure and they might not be able to if there’s no amyloid left in the brain. We will continue to research this topic and report on our findings. Take care!

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