New Alzheimer’s drug, donanemab – what is it and how does it work?
Note: This blog was updated on 19/07/2023 after Eli Lilly & Company released the full results of their donanemab clinical trial.
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. It was only a few months ago that we heard about lecanemab – the first drug to successfully tackle the disease itself – and we already have another on the horizon. Although, like lecanemab, the effects of donanemab are modest, 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 every month.
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.
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. Based on these new phase 3 results, Lilly will proceed with global regulatory submissions as quickly as possible and anticipates making a submission to the US drug regulator (the FDA) in the coming months. We do not expect to hear a decision from the UK’s regulator (the MHRA) until 2024, 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. 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, the only donanemab trial still recruiting in the UK is run by a private clinical trials organisation called Re:Cognition Health.
You can find out more by calling the Dementia Research Infoline on 0300 111 5 111 (9-5pm Monday to Friday). You can also register to Join Dementia Research here. The registration process takes 10-15 minutes over the phone.
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.