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Alzheimer drugs: How donanemab compares to lecanemab

May 6, 2023

Drug developers are making progress with treatments for Alzheimer's disease, one of the leading causes of dementia.

Illustration of a paper cut out of a human dead and a puzzle piece symbolizing the complexities of the brain
So much is unknown: Alzheimer's disease is one of the hardest conditions to treatImage: Berit Kessler/Zoonar/picture alliance

Just five months after the US Food and Drug Administration (FDA) granted "accelerated" approval for a drug to treat Alzheimer's disease, developed by Biogen and Eisai and called lecanemab, another pharmaceutical company, Eli Lilly, has released what it calls "positive results" from phase 3 trials for its own candidate Alzheimer's treatment, donanemab.

In a press release published May 3, Eli Lilly said donanemab had "significantly slowed cognitive and functional decline in people with early symptomatic Alzheimer's disease."

Eli Lilly has yet to publish the full results, which means the data has not been peer reviewed or independently verified, so experts have only been able to comment on the press release.

In the United States, the Alzheimer's Association's chief science officer Maria Carrillo said, "these are the strongest phase 3 data for an Alzheimer's treatment to date."

And the association Alzheimer Europe has also welcomed the news.

But writing for the journal Science, Derek Lowe, who works in drug discovery, commented that "we are surely looking at the most optimistic take possible  we'll have to wait for filing with the FDA to see more."

Eli Lilly says it aims to present its results at a conference in July and submit the drug for FDA approval around the same time.

Goal to treat Alzheimer's and other forms of dementia 

Alzheimer's disease affects at least 55 million people worldwide. 

The World Health Organization says Alzheimer's disease is the most common form of dementia — "dementia is the seventh leading cause of death and one of the major causes of disability and dependency among older people globally."

Dementia is one of the hardest conditions to treat. As a result, pharmaceutical companies have been known to stop their research when it's unprofitable and they see their chances of success as low. 

But there is a renewed push to find treatments for Alzheimer's. The US National Plan to Address Alzheimer's Disease aims to "prevent and effectively treat Alzheimer's disease by 2025."

The FDA says it "may approve drugs for serious conditions where there is an unmet medical need," which would explain lecanemab's fast approval, but that doesn't mean the FDA lowers its standards in such cases.

In January, the FDA denied an Eli Lilly request for accelerated approval for donanemab. The FDA said it needed safety data from more patients.

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How does donanemab work?

Donanemab is not the first of its kind. As with similar antibody-based therapies such as lecanemab, donanemab is not a cure for Alzheimer's.

Instead, they are antibodies that target different forms of amyloid-beta (Aβ) proteins that can clump together to form amyloid plaques in people's brains, resulting in their cognitive decline.

The drug aims to remove the plaques from the brain and slow the progression of the disease.

"Nearly half (47%) of the participants on donanemab, compared to 29% on placebo, had no clinical progression at 1 year," said the Eli Lilly press release. "[The drug] resulted in 40% less decline on the ability to perform activities of daily living."

A placebo is a non-active substance that is used to compare results with an active substance — that is, the one that is being tested.

How does donanemab compare to lecanemab?

Eli Lilly's press release suggests that donanemab slows cognitive decline by 35%. Lecanemab trial results showed it slowed cognitive decline by 27%.

Both drugs are given intravenously, but the doses are different — donanemab was given every four weeks and lecanemab every two weeks.

Both drugs were only tested on people with early stages of Alzheimer's. It is, therefore, unknown how effective the drugs are for people with more advanced forms of the disease.

Lecanemab is approved in the US, but it is still under evaluation by the FDA's counterpart in Europe, the European Medicines Agency (EMA).

At time of writing, donanemab was not approved for use in either the US or Europe.

Three deaths in the donanemab trials

Both donanemab and lecanemab have a high-risk of side effects, wrote the journal Nature in a May 4 news article.

The side effects include "amyloid-related imaging abnormalities" — or ARIA — which include swelling or bleeding in the brain.

Eli Lilly reported swelling of the brain in 24% of trial participants and bleeding in the brain in 31% of its participants.

Three patients died because of these side effects, the company said.

"The majority of ARIA cases were mild to moderate and resolved or stabilized with appropriate management," said the company. The incidence of serious ARIA cases was 1.6%.

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"ARIA is usually asymptomatic, although serious and life-threatening events can occur," said Frank Jessen, director of the Clinic and Polyclinic for Psychiatry and Psychotherapy at the University of Cologne, Germany. 

Lecanemab's phase 3 results showed that 17% of participants had brain bleeds and 13% had brain swellings, which is less than donanemab. But Biogen and Eisai, the companies behind lecanemab, have also reported three deaths associated with the drug.

Edited by: Zulfikar Abbany