New Alzheimer’s drug, donanemab – what is it and how does it work?

Researcher smiling
Researcher smiling

By Emma Taylor | Thursday 04 May 2023

Note: This explainer was updated on 3rd July 2024 in response to the US Food and Drug Administration’s decision to approve donanemab (Kisunla).

In May 2023, pharmaceutical company Eli Lilly & Company (Lilly) released the positive initial results of a clinical trial into a new Alzheimer’s drug, donanemab. You may also hear donanemab be called its brand name, Kisunla.

Like lecanemab – the first drug to successfully tackle Alzheimer’s disease itself – the effects of donanemab are modest. But it shows how fast dementia research is accelerating towards a cure.

We know that this news will spark lots of questions, so we’ve answered some of the most commonly asked questions to our Dementia Research Infoline and across our social media channels below.

 

What is donanemab?

Donanemab, like lecanemab, is a type of drug called a monoclonal antibody. Antibodies form part of our immune system and bind to harmful proteins to destroy them. Donanemab contains antibodies that bind to a protein called amyloid, which builds up in the brain in the early stages of Alzheimer’s disease. Unlike currently available treatments, which can only relieve symptoms, donanemab is a so-called ‘disease-modifying’ treatment that is designed to tackle the underlying disease.

The drug is delivered via an infusion, meaning people on the trial needed to spend several hours in a clinic once a month. This is different to lecanemab, which is delivered every two weeks.

Scientists have long suspected that clearing amyloid from the brains of people with Alzheimer’s will slow down the disease, and allowing them to live independently and with milder symptoms for longer. The results for both drugs confirm this idea.

 

 

How effective is donanemab?

Lilly’s TRAILBLAZER ALZ-2 clinical trial shows that donanemab was able to slow the rate of decline in people’s cognition and function over a year. This included memory, thinking and ability to carry out daily activities.

The international trial included over 1,700 participants with early Alzheimer’s disease. It tested donanemab against a dummy drug (placebo) to see how well it worked at slowing down the progression of the disease and whether it was safe. Participants were deemed to have completed their course of treatment with donanemab once the amyloid levels in their brains dropped below a certain threshold, as measured by a scan. Once this had happened, participants were switched to the placebo for the remainder of the trial.

After one year, participants were tested against several measures of memory and thinking, and again at eighteen months.

  • According to Lilly, donanemab slowed decline associated with Alzheimer’s by around a third (35%) compared with placebo in people whose brain scans showed they had low-medium levels of a protein called tau. The drug also resulted in 40% less decline in the ability to perform activities of daily living, such as managing finances, driving and carry out hobbies.
  • Donanemab had no significant effect in people with high levels of tau.
  • Almost half (47%) of those on donanemab had no clinical progression of disease after a year, compared with 29% on placebo.
  • Furthermore, participants on donanemab had a 39% lower risk of progressing to the next stage of disease compared to placebo.
  • Lilly also showed that, for a small group of around 200 people on the trial who were in the very earliest stage of cognitive impairment, the drug appeared to work very well. However because the number of participants in this group was so small, it’s very hard to be sure that the rate of slowing seen here, 60%, is a ‘real’ result. Nevertheless, some newspapers reported this number in their headline coverage.

As with many medial research studies, the study population was primarily White (91.5%), which may limit generalisability to other populations due to a lack of racial and ethnic diversity.

We don’t know what this means in the long run as the trial only lasted for 18 months. Future studies carried out by Lilly will look at the long-term effects of the drug, as well as its effects in people with different stages of Alzheimer’s disease.

 

Is donanemab safe?

Both lecanemab and donanemab cause a concerning and poorly understood side effect called ARIA (which stands for ‘amyloid related imaging abnormalities’). The name describes changes to brain structure and swelling or bleeding, seen on MRI brain scans, which – for some – can be serious.

In those patients receiving donanemab, brain swelling was seen on the scans of one in four participants, with one in 20 experiencing symptoms. According to Lilly, less than two in every 100 participants experienced serious brain swelling after taking donanemab. However, this included two participants whose deaths were attributed to the condition and a third who died after an incident of serious brain swelling.

Brain bleeding was seen in around one in three of the donanemab group and around three in every 20 in the placebo group. It said most cases of swelling or bleeds were “mild to moderate” and responded to treatment.

Nevertheless, ARIA is poorly understood – including whether it can become more serious over time. So, the risk associated with drugs like donanemab and lecanemab are something which is being closely monitored in longer-term studies and will be taken account by regulators when they decide whether to approve these drugs.

Beyond ARIA, other side effects people taking donanemab had included reactions from the intravenous drip needed to give the infusion, which is not uncommon with these types of drug.

Ongoing studies are investigating its safety further.

Three deaths during the trial were attributed to donanemab-induced ARIA, and one additional death was attributed to the placebo drug.

 

Will this drug work on other types of dementia, such as vascular dementia or dementia with Lewy bodies?

At the moment, donanemab is only intended for people with Alzheimer’s disease. That’s because it targets amyloid, which scientists believe plays an important role in the development of Alzheimer’s. It is not thought to be as important in other types of dementia, so it is unlikely to work against other diseases that cause dementia.

Beyond donanemab, there are over a hundred drugs in clinical trials across the world investigating treatments for all types of dementia. At Alzheimer’s Research UK, we believe it is a question of when, not if, treatments for other types of dementia will become available.

 

How are the drugs that target amyloid, like lecanemab and donanemab, different?

Amyloid plaques build up in the brain in stages. Different anti-amyloid drugs bind to the protein at different stages. We still don’t know why this makes some drugs more effective at treating symptoms than others.

 

 

Lecanemab targets amyloid as it begins to form fibres, whereas donanemab binds to amyloid once these fibres have clumped together to become a larger plaque in the brain. A third drug, aducanumab – which caused controversy when it became available in the US in 2021, and which isn’t approved in the UK – targets both.

Donanemab is now the second drug that has been shown to tackle the underlying disease itself, to slow the development of Alzheimer’s disease. However, we can’t compare these drugs directly as the two trials are very different so it’s impossible to say anything concrete.

Unlike lecanemab, people are not required to continue taking donanemab once it has cleared the protein amyloid from the brain.

This means that people taking donanemab do not need to stay on the drug for extended periods of time. In trials, almost half of people taking donanemab were able to stop taking the drug within a year.

At what stage of diagnosis could donanemab be given?

Donanemab has been designed for people in the early stages of Alzheimer’s disease. People included in the trials of this drug had mild cognitive impairment or mild Alzheimer’s disease, confirmed by a test of their spinal fluid or a PET brain scan showing a build-up of amyloid in their brain. Many experts suspect it would be unlikely to work in later stages of the disease, although this hasn’t been tested in trials yet.

Is lecanemab available in the USA?

The US Food and Drug Administration (FDA) granted a licence to Lilly to allow it to market donanemab to people with a confirmed diagnosis of mild cognitive impairment (MCI) or early-stage Alzheimer’s disease in the US on July 3rd, 2024.

The FDA’s recommendation was based on their independent review of data from Lilly’s RAILBLAZER-ALZ 2 Phase 3 clinical trial, which was published in July 2023.

In January 2023, donanemab was rejected under the FDA’s more limited ‘accelerated’ approval programme.. The FDA needed to see data showing the drug was safe to take over 18 months, but most people had finished their course by then. So, Lilly did not have enough evidence from people who had taken the drug for 18 months or more to present to the FDA.

Accelerated approval would only have enabled US residents with appropriate medical insurance, or those who could afford to pay for it directly, to access the drug.

July’s ruling enables the Centers for Medicare and Medicaid Services (CMS) to provide insurance coverage under the US government’s Medicare plan, which covers older people with limited income and resources.

The FDA’s prescribing information for donanemab includes a warning for doctors to monitor for side-effects including ARIA, as well as infusion related reactions. This means that people taking donanemab must receive regular MRI brain scans.

The prescribing information also mentions that testing for ApoE4 (an Alzheimer’s risk gene) may be performed before starting treatment to inform the risk of developing ARIA.

Finally, some people taking medications to prevent blood clots, called antithrombotic medicines, may be at higher risk of ARIA. People with any concerns about donanemab in the US should talk to their doctor.

Does Alzheimer’s Research UK support people travelling to the US to access lecanemab?

The health systems in the US and UK work very differently, and if people are to travel to the US to try to access treatment it would be at great personal cost. Although we realise the people with Alzheimer’s and their families in the UK are eager for effective new treatments, it’s important that the UK regulator carries out its own rigorous, independent assessment of Lilly’s data. We are urging for this to happen as quickly as possible without compromising the quality of the evaluation.

Will it become available in the UK?

To be able to sell a drug in a particular country, a drug’s manufacturer needs to apply for a license. We do not expect to hear a decision from the UK’s regulator (the MHRA) until later this year, but you can sign up to our newsletters to be notified when we know more. If the MHRA approve donanemab, it will likely become available privately without much delay.

To become available on the NHS, licensed drugs then need to be assessed for cost-effectiveness by the National Institute for Health and Care Excellence (NICE) in England and Wales, and the Scottish Medicines Consortium in Scotland.

We are not yet sure when we can expect these decisions, but it is likely to be at least a couple of years before a treatment (whether lecanemab, donanemab or another treatment) is available on the NHS.

It is important to note that donanemab requires infusions every month – meaning that people would need to get to a hospital or specialist centre monthly to receive treatment. They would also need to have had a PET scan or lumbar puncture to confirm they were amyloid positive.

So, as well as licensing and approval by organisations like NICE and Scottish Medicines Committee, the NHS itself will need to undergo significant changes in order to deliver a drug like donanemab. This includes setting up infusion clinics in which to give the treatment to patients, and much greater capacity to offer people PET scans or lumbar punctures to make sure they’re eligible for the drug.

Right now, our best available data suggests that only a small percentage of patients receive these routinely – as low as 2%. That needs to change.

While taking the drug, people will likely need regular monitoring for side effects like ARIA, which involves MRI scans too – and we know that the NHS currently is very low on capacity for this too.

Given the large number of people who may be eligible for donanemab in the UK, this is likely to be very expensive and require a large amount of resource. This will all need factoring into any decisions around these drugs, and it’s likely this will not be a straightforward and quick process.

People living with Alzheimer’s deserve access to safe and effective treatments urgently. That’s why Alzheimer’s Research UK has written to Lilly, calling on them to put donanemab forward for regulatory review in the UK without delay. And this review should be conducted by the UK regulators as a priority. Alzheimer’s Research UK will work with the NHS, NICE and the Scottish Medicines Consortium to discuss any concerns and highlight ways forward that ensure patients don’t need to wait any longer than necessary to benefit from any new drug.

How expensive will donanemab be?

The price of donanemab is not currently confirmed, but we know that another similar drug called lecanemab could cost around £21,000 per person per year through private clinics, should it be granted a license in the UK.

Below are Lilly’s predictions for how much donanemab (Kisunla) will cost in the US. Each vial of the drug costs almost $700.

For someone taking donanemab for 6 months, they would need 6 infusions with an overall cost of $12,522. Someone taking donanemab for 12 months would need 13 infusions, with an overall cost of $32,000. Someone taking donanemab for 18 months would need 19 infusions, with an overall cost of $48,696.

Donanemab is more expensive than lecanemab, which costs patients an estimated $26,500 a year. But patients don’t stop taking lecanemab.

The overall cost of donanemab for each person will depend on how long they are on it.

Medicare Part B will pay some of the cost. People taking the drug will have to pay a20 percent coinsurance after meeting their deductible.

Lecanemab’s manufacturer, Eisai, released their reasoning behind this price, which you can read here. Whether either drug will be available on the NHS is not yet known.

How can I get involved in a trial?

The best way to find out about taking part in dementia research studies, including clinical trials, is through a nationwide register called Join Dementia Research. When you register, you provide some personal details about your health, age and contact details. These details are then used to match you to studies that you are suitable to take part in.

Signing up to the register is not a commitment to take part in any particular study, it just allows research studies to find willing volunteers.

Currently, there is a donanemab trial recruiting through Join Dementia Research. You can register to Join Dementia Research here.

You can also find out more by calling the Dementia Research Infoline on 0300 111 5 111 (9-5pm Monday to Friday).

If you have recently been diagnosed with mild cognitive impairment or Alzheimer’s disease and would like to share your story to inspire others or help shape our work please get in touch via stories@alzheimersresearchuk.org

What is Alzheimer’s Research UK doing to bring forward new treatments?

At Alzheimer’s Research UK, we won’t rest until we have found cures for the diseases that cause dementia. Although drugs like donanemab and lecanemab are promising, their effects are modest and they don’t stop the disease from progressing entirely. We’ll likely need to combine these drugs with others that target other processes beyond amyloid to make transformational progress.

So, we need to keep exploring other treatment avenues in order to find the next generation of effective treatments. Initiatives like our Drug Discovery Alliance, which brings together world-leading scientists from the Universities of Oxford and Cambridge, and University College London, are crucial to unlocking these other routes to treating Alzheimer’s and other types of dementia. You can hear about emerging treatments from some of the researchers themselves, in our recent Lab Notes event here.

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2 Comments

  1. Victor on 17th April 2024 at 8:45 am

    Hello,
    My Mother has Dementia. We have noticed that watching TV has various effects on mum’s behaviour.
    We know that different types of Light has an effect on peoples moods.
    Could there be some form of ‘Light Frequency ‘ that might help Dementia sufferers?
    Thank you.

    • Alzheimer's Research UK on 19th April 2024 at 2:29 pm

      Hi Victor, sorry to hear about your mother. There is some small-scale research which has investigated using light therapy for people with dementia. One small study on 25 people found that one hour of morning blue light therapy improved cognition and sleep in people with Alzheimer’s disease compared to those who didn’t have the therapy. There is also currently a clinical trial investigating if light flickering at a rate of 40 flashes per second combined with cognitive therapy could help people affected by Alzheimer’s disease. More details of this study can be found here: https://clinicaltrials.gov/study/NCT03657745. More research is needed though, as until large scale clinical trials called randomised control trials investigate light therapy as a dementia treatment further, we can’t be sure of it’s benefits.

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About the author

Emma Taylor

Senior Information Officer

Team: Information services