Can new drug donanemab really slow the growth of Alzheimer's disease?

There is a possibility that a new Alzheimer’s treatment will enter the market with clear evidence that it can halt the mind-robbing condition by about 60 per cent.

The US pharmaceutical giant, Eli Lilly has applied for the United States Food and Drug Administration approval of its new experimental drug.

The application is based on positive phase three clinical trial results on donanemab, which significantly slowed the disease progression in patients at the early stages.

According to Dailymail, experts also think it put an end to the long-running argument over whether the buildup of sticky plaques or amyloid, is at least partially to blame for the degenerative illness.

Let’s take a closer look.

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Alzheimer’s new drug for mildly impaired patients

An experimental drug named donanemab works best if Alzheimer’s patients are treated as early as possible, ideally before they develop symptoms of the brain-wasting disease, researchers said on Monday, in the latest promising development for treating the most common form of dementia, according to Reuters.

The drug, which is the second treatment after lecanemab, has been shown to slow the progression of memory and thinking problems by about a third, but that rate doubles to 60 per cent if the drug is started when patients are only mildly impaired, according to new trial data presented at the Alzheimer’s Association International Conference in Amsterdam.

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The full analysis from the study involving more than 1,700 patients showed that results were less robust for older, later-stage patients as well as those with higher levels of a protein called tau that has been linked to Alzheimer’s disease progression.

The findings underscore that “earlier detection and diagnosis can really change the trajectory of this disease,” said Anne White, president of neuroscience at Lilly.

Donanemab, like the recently approved Leqembi from Eisai (4523.T) and Biogen (BIIB.O), is an intravenous antibody designed to remove deposits of a protein called beta-amyloid from the brains of Alzheimer’s patients.

Referring to Lilly’s data released on Monday, Dr Susan Kohlhaas, executive director of research and partnerships at Alzheimer’s Research United Kingdom, said, “These results provide further confirmation that removing amyloid from the brain can change the course of Alzheimer’s, and may help people affected by this devastating disease if they’re treated at the right time.”

Dr Richard Oakley, associate director of research and innovation at Alzheimer’s Society, told Dailymail, “This is truly a turning point in the fight against Alzheimer’s and science is proving that it is possible to slow down the disease. Treatments like donanemab are the first steps towards a future where Alzheimer’s disease could be considered a long-term condition alongside diabetes or asthma - people may have to live with it, but they could have treatments that allow them to effectively manage their symptoms and continue to live fulfilled lives.”

Its side effects

Lilly’s study showed that brain swelling, a known side effect of amyloid-clearing antibodies, occurred in more than 40 per cent of patients with a genetic predisposition to develop Alzheimer’s. The company had previously reported that 24 per cent of the overall donanemab treatment group had brain swelling. Brain bleeding occurred in 31 per cent of the donanemab group and about 14 per cent of the placebo group.

The deaths of three trial patients were linked to the treatment, researchers reported.

“These side effects should not be taken lightly,” but most cases were manageable by monitoring with magnetic resonance imaging (MRI) or stopping the drug, said study investigator Dr Liana Apostolova, professor in Alzheimer’s Disease research at Indiana University School of Medicine. Doctors are likely to use “very stringent MRI safety screening while we treat these patients,” she added.

Lilly said donanemab’s treatment effect continued to increase relative to placebo over the course of the 18-month trial, even for participants who had been taken off the drug after their levels of amyloid deposits fell significantly.

“At the end of the trial, the average patient had been without the drug for seven months and yet they continued to benefit,” White said, adding that the findings support the idea that donanemab can be stopped once amyloid is cleared from the brain.

“Some patients did not worsen significantly during the trial and on average progression of disease was slowed 4.4-7.5 months over 18 months,” said Dr Liz Coulthard, associate professor in dementia neurology at the University of Bristol.

Lilly said in May that the study had met all of its goals, showing that donanemab slowed cognitive decline by 29 per cent compared to a placebo in people with mild cognitive impairment or mild dementia whose brains had deposits of two key Alzheimer’s proteins, beta-amyloid and tau. For high tau patients, donanemab was shown to slow disease progression by about 17 per cent, while the benefit was 35 per cent for those with low-to-intermediate tau levels.

Health regulators’ approval needed

Eli Lilly on Monday said that it applied for full United States Food and Drug Administration approval of its Alzheimer’s treatment, donanemab, and expects the agency to make a decision by the end of this year.

It said submissions to other global regulators are underway, and most will be completed by year-end.

“If the drug is approved in the UK, then NHS services will need to adapt considerably to provide it, and there will need to be an honest discussion between patients, carers, and doctors about the benefits and risks associated with this type of treatment,” Professor Paresh Malhotra, head of neurology at Imperial College London told Dailymail.

Before drug watchdog NICE evaluates whether both medications are cost-effective for the NHS, the UK-based Medicines and Healthcare Products Regulatory Agency (MHRA) will first investigate whether they are safe for use in the country.

The health service will have time to prepare for any widespread roll-out because these processes are likely to take at least 18 months.

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Other breakthrough drugs

The FDA this year granted standard approval to Leqembi, the first Alzheimer’s disease-modifying treatment to achieve that goal, clearing the way for wider insurance coverage of the drug. It’s for patients with mild or early cases of dementia tied to Alzheimer’s disease.

According to The Associated Press, the drug, made by Japan’s Eisai and its US partner Biogen, is designed to target and clear away a sticky protein called beta-amyloid that builds up into brain-clogging plaques – one key hallmark of Alzheimer’s disease.

It targets a slightly different form of that amyloid, possibly explaining why it proved successful in a rigorous study while a long list of prior amyloid-targeting drugs has failed, said Dr Sam Gandy, an Alzheimer’s expert at New York’s Mount Sinai Hospital.

The FDA also cleared a similar drug named Aduhelm in 2021 even though studies never proved it really helped patients, a move that triggered scathing criticism from a congressional investigation.

Both medications are also being studied in large trials to see if they have an impact on delaying the onset of Alzheimer’s disease symptoms.

According to Alzheimer’s News Today, there are over 44 million people worldwide living with brain-wasting disease or a related form of dementia.

In India, more than four million people have this disease, as per Alzheimer’s Association.

With inputs from agencies