Patients' anguish as FDA delays decision to approve Eli Lilly's 'life-changing' Alzheimer's drug - due to concerns about deadly side effects and how medicine was tested

An unexpected move by the FDA to delay approval of a potentially life-changing Alzheimer’s drug has let down doctors and patients eagerly awaiting its availability. 

Eli Lilly, the maker of the drug known as donanemab, said the approval would be delayed beyond March as the FDA plans to call a last-minute meeting of outside experts to review its safety and efficacy.

The medicine had been expected to obtain approval by the end of the first quarter of the year, after clinical trials showed that it was able to modestly slow the rate of cognitive decline associated with the disease.

But the FDA wants an independent view on the drug's major side effect - it can cause fatal brain swelling.

Donanemab was shown to slow down cognitive decline by 60 percent in patients in early stages of disease 

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

The FDA wants outside experts to examine the company’s unique trial design, which allowed patients to stop taking the drug once plaques believed to cause Alzheimer’s were cleared from the brain. 

The move is a setback for Alzheimer’s sufferers and their advocates, who are urging the FDA to take swift action to do all it can to approve the drug. 

Professor Robert Howard, an expert in geriatric mental health at the University College London, said: 'This is very bad news for Lilly. 

'The longer [competitor] lecanemab has a licence but donanemab doesn't, the more the available (but limited) US capacity to treat patients with amyloid antibodies will be blocked (for 18 months) by the first drug to hit the market.'

Donanemab belongs to a growing class of drugs that aim to reduce clumps of a sticky protein called beta-amyloid, which is believed to be a primary driver of this particular type of dementia.

In the company’s clinical trial, the monthly injection, 60 percent of patients showed a slowdown in cognitive decline after a year of taking it based on criteria of one type of symptom rating scale, and by 46 percent per another scale.

Among patients with early Alzheimer's whose brain scans showed low or medium levels of a protein called tau, the drug was found to slow clinical decline by 35 percent.

Levels of tau are another marker of how far the disease has progressed. There is debate in the field of dementia research over whether amyloid buildup is the cause of the disease or if it’s tau.

This protein undergoes abnormal changes in the brain and becomes tangled with other strands of proteins. The build-up of these tangles impedes brain cells from effectively communicating with each other.

The FDA’s decision was a blow to advocates like the Alzheimer’s Association.

A spokesperson from the advocacy group said: ‘While the decision is a surprise at this stage in the review process, the safety and appropriate administration of treatments is paramount.

I'm taking a game-changing Alzheimer's drug - I'm sure it will work

Mike Colley started having problems with his memory and decision making a couple of years ago. He is one of only a few dozen UK patients to be part of the global trial of donanemab. 

‘On behalf of everyone who could benefit from this treatment, we strongly urge the FDA to move swiftly in this next stage of its review.’

The drug, as well as a similar treatment Leqembi by Biogen, is meant for people with mild cognitive impairment in the early stages of Alzheimer’s. Around six million Americans have the disease, and roughly 300,000 are in the early stages and would likely qualify for the drug.

The field of Alzheimer’s treatment development has been plagued with failures over safety concerns, brain bleeds and swelling being chief among them, as well as doubt that they would actually work.

Past studies have shown only mild declines in the speed at which the disease causes the mind to waste away, which has instilled doubt in the minds of reviewers charged with approving or denying the drug companies’ applications.

Still, plenty of evidence shows that some of the nearly 1,800 people enrolled in Lilly’s trial have benefitted from the drug, including Connecticut native Jim Sirois, now 68.

He was diagnosed with early-onset Alzheimer's in 2020 after struggling to speak and becoming so forgetful he couldn't remember where he had been the day before. But his wife said the drug effectively halted the condition over the span of 2023.

Jim Sirois and his wife Sue. Jim was diagnosed with early-onset Alzheimer's more than three years ago and, since starting donanemab, his disease 'really hasn't progressed'

Myra Garcia, from southern California, pictured above with her husband Richard, was also put on the drug after being diagnosed with early-onset Alzheimer's. She told DailyMail.com that everyone who gets the chance should take the drug

Sue Sirois, 64, said: 'I compare Jim's decline to a friend I know who was diagnosed with Alzheimer's at age 56. She died recently, and only lasted six years, whereas Jim is now over three years in and he is now still pretty much the same as what he was.'

Other patients in the drug's trials hailed it as helping them to continue doing 'normal things' like going to classes and doing the laundry.

Myra Garcia, 64, from southern California, is also receiving donanemab after being enrolled in a separate trial. She told DailyMail.com that she would get the drug approved tomorrow if she could, adding that it ‘has worked beautifully.’

She added: 'I am in three choirs, my church choir, the Hillcrest choir, and a Bach choir.

'I also exercise with my husband, we do something together every morning, but then I do cooking and laundry and the things that everybody does.'