How does donanemab fight Alzheimer’s? And when will it be approved in the UK and US? Everything you need to know about game-changing new drug
- Donanemab slowed cognitive decline in Alzheimer’s patients by 35.1 per cent
- But what is the treatment? Is it safe? And what do results actually show?
It’s been labelled a ‘milestone’ in the fight against Alzheimer’s.
But what is donanemab? How does the drug work? And what do the results actually show?
Here, MailOnline answers all of your questions.
Donanemab is given to Alzheimer’s patients through an IV infusion once a month. The monoclonal antibody — a man-made version of proteins produced by the body to fight-off harmful substances — travels to the brain . Once inside the organ, donanemab binds to toxic build-ups of amyloid plaque — a hallmark sign of the memory-robbing disease. This prompts immune cells, known as microglia, to clear them
Researchers today unveiled that donanemab slowed cognitive decline in Alzheimer’s by 35 per cent by removing toxic plaques in the brain
The failed Alzheimer’s drugs
Eli Lilly abandoned trials of would-be Alzheimer’s therapy solanezumab in January 2018 because the effects it was having were of no statistical significance.
Merck stopped a late-stage human trial of the drug verubecestat in February 2018 because a safety analysis said the benefit-to-risk ratio was not good enough.
Johnson & Johnson stopped trials of its experimental Alzheimer’s drug atabecestat in May 2018 because of safety issues. Some patients started to show signs of liver damage and the scientists decided the trial was too risky to continue.
In 2018, Pfizer completely stopped trying to develop dementia treatments after a number of unsuccessful attempts, notably of Alzheimer’s drug bapineuzumab in 2012.
Roche halted two late-stage human trials of crenezumab, which it hoped would slow early Alzheimer’s, because a mid-study analysis said it was unlikely to work, the company announced in January 2019.
Amgen and Novartis abandoned an Alzheimer’s drug called CNP520 in July 2019 because patients’ symptoms continued to get worse when they were taking the treatment.
Biogen and Eisai, who developed the new drug lecanemab, scrapped two late trials of Alzheimer’s treatment elenbecestat in September 2019.
How does it work?
Donanemab is given to Alzheimer’s patients through an IV infusion once a month.
The monoclonal antibody — a man-made version of proteins produced by the body to fight-off harmful substances — travels to the brain.
Once inside the organ, donanemab binds to toxic build-ups of amyloid plaque — a hallmark sign of the memory-robbing disease.
This prompts immune cells, known as microglia, to clear them.
Patients stop taking donanemab once the amyloid accumulation has been cleared from their brain.
Half of participants in a trial of the drug reached this point after one year, and seven in 10 stopped taking it within 18 months.
What did trial results show?
Eli Lilly, the US pharmaceutical firm behind the treatment, boasted that donanemab significantly slowed cognitive and functional decline for patients in the early stages of Alzheimer’s.
Researchers examined almost 1,800 people with early-stage Alzheimer’s, when the tell-tale memory loss first begins but before the cruel disease has managed to fully take hold.
All had a build-up of amyloid in their brain — one of the two main proteins thought to interfere with the communication between brain cells among patients with dementia.
Half of the volunteers received a monthly infusion of donanemab while the others were given a dummy drug, known as a placebo, over 18 months.
Donanemab was found to slow ‘clinical decline’ by 35.1 per cent in patients whose brain scans showed low or medium levels of tau — the second protein thought to drive Alzheimer’s.
It means people with disease could still perform day-to-day tasks, such as shopping, housekeeping, managing finances and taking medication.
And 47 per cent saw no progression in their Alzheimer’s one year later.
When the results were combined for people who had different levels of tau, there was a 22.3 per cent slowing in disease progression, on average.
The final results from Phase 3 TRAILBLAZER-ALZ 2 study were presented today at the Alzheimer’s Association International Conference in Amsterdam.
Participants who took donanemab also had 84 per cent lower amyloid levels after 18 months, compared to a one per cent drop among the placebo group.
Is the drug dangerous?
Like any treatment, donanemab is not without risks.
Researchers found some serious side effects, such as brain swelling.
Brain bleeds occurred in 314 patients (36.8 per cent) in the donanemab group and 130 patients (14.9 per cent) in the placebo group.
From 1906 when clinical psychiatrist Alois Alzheimer first reported a ‘severe disease of the cerebral cortex’ to uncovering the mechanics of the disease in the 1980s-90s to today’s ‘breakthrough’ drug lecanemab, scientists have spent over a century trying to grapple with the brutal disease that robs people of their cognition and independence
Vaccines and antibodies, brain zapping helmets, oxygen therapy and stem cells are just some of the areas experts are exploring in the hunt for a cure for Alzheimer’s
In the group that received donanemab, three participants (0.4 per cent) died, which researchers said was linked to their treatment.
For comparison, there was one treatment-related death (0.1 per cent) in the placebo group.
Deaths have also occurred in trials of other similar, rival drugs, sparking concern among some experts who have said they wouldn’t feel comfortable telling their patients that the drug is safe.
Those who were given the drug were also more likely to have an infusion-related reaction, such as a fever, vomiting and headaches (9 per cent vs 0.5 per cent).
And 112 patients taking donanemab withdrew due to the side effects, compared to just 38 withdrawals among the placebo group.
When will it be available?
Eli Lilly has submitted data to the US Food and Drug Administration (FDA) and expects it to make a decision by the end of the year.
It is also applying to other regulators for approval, including the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).
If approved by the MHRA, donanemab would need to be assessed by the National Institute for Health and Care Excellence (NICE) before it could be rolled out on the NHS. This process could take a couple of years.
Another Alzheimer’s drug, lecanemab, which works in a similar fashion, was last month approved in the US.
How is it different to other new Alzheimer’s drugs?
Donanemab — which has yet to be given a brand name — works by binding to amyloid after it has formed plaques in the brain.
Lecanamab, also known as Leqembi, targets the protein as it begins to form fibres in the organ.
Less than a year ago, another drug, called lecanemab (pictured), was found to slash cognitive decline among those with the memory-robbing condition by 27 per cen t
Meanwhile, aducanumab attaches to amyloid at both stages.
Lecanamab and aducanumab were developed by Japanese and US pharmaceutical firms Eisai and Biogen.
Lecanamab has already been approved in the US but is still being examined by UK regulators.
Aducanumab was given the green light in the US but rejected by EU officials over concerns that, despite early studies showing promise, aducanumab had failed in clinical trials to show any major improvements in patients’ symptoms.
Isn’t there already drugs for Alzheimer’s?
Current Alzheimer’s drugs only temporarily improve some symptoms.
One option is Acetylcholinesterase (AChE) inhibitors, which increase levels of acetylcholine — a substance in the brain that helps nerve cells communicate.
This can boost patients’ memories, as well as helping them think more clearly and better manage daily activities.
Meanwhile, memantine blocks the effects of an excessive amount of a chemical in the brain called glutamate.
It can improve memory, helping sufferers remember recent conversations, where they put things and ease delusions or anxiety.
Additionally, there are medicines that can be taken to treat behaviour changes such as anxiety, agitation and aggression.
What is Alzheimer’s and how is it treated?
Alzheimer’s disease is a progressive, degenerative disease of the brain, in which build-up of abnormal proteins causes nerve cells to die.
This disrupts the transmitters that carry messages, and causes the brain to shrink.
More than 5 million people suffer from the disease in the US, where it is the 6th leading cause of death, and more than 1 million Britons have it.
WHAT HAPPENS?
As brain cells die, the functions they provide are lost.
That includes memory, orientation and the ability to think and reason.
The progress of the disease is slow and gradual.
On average, patients live five to seven years after diagnosis, but some may live for ten to 15 years.
EARLY SYMPTOMS:
- Loss of short-term memory
- Disorientation
- Behavioral changes
- Mood swings
- Difficulties dealing with money or making a phone call
LATER SYMPTOMS:
- Severe memory loss, forgetting close family members, familiar objects or places
- Becoming anxious and frustrated over inability to make sense of the world, leading to aggressive behavior
- Eventually lose ability to walk
- May have problems eating
- The majority will eventually need 24-hour care
HOW IT IS TREATED?
There is no known cure for Alzheimer’s disease.
However, some treatments are available that help alleviate some of the symptoms.
One of these is Acetylcholinesterase inhibitors which helps brain cells communicate to one another.
Another is menantine which works by blocking a chemical called glutamate that can build-up in the brains of people with Alzheimer’s disease inhibiting mental function.
As the disease progresses Alzheimer’s patients can start displaying aggressive behaviour and/or may suffer from depression. Drugs can be provided to help mitigate these symptoms.
Other non-pharmaceutical treatments like mental training to improve memory helping combat the one aspect of Alzheimer’s disease is also recommended.
Source: Alzheimer’s Association and the NHS
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