FDA Advances Potentially Revolutionary Alzheimer’s Treatment

Pharmaceutical giant Eli Lilly just cleared one of the final hurdles for approval of a new “early-stage” Alzheimer’s treatment called donanemab. Should the drug receive the final green light, it would be only the second FDA-approved drug for treatment of Alzheimer’s.

Alzheimer’s currently affects more than six million Americans, the vast majority of whom are aged 65 and older. There is no known cure, and no approved treatments are currently available to slow memory loss or reverse the effects of the disease. Alzheimer’s causes the brain to shrink and is the most common cause of dementia, which leads to significant psychological distress in its victims before they pass. Early symptoms include forgetfulness, losing one’s place in a conversation, and a loss of the ability to perform common tasks.

However, donanemab has provided fresh hope for those suffering from Alzheimer’s and those who will develop it in the future. The drug, which is administered intravenously once a week, could hit the market within the next year.

Eli Lilly expected donanemab to be approved earlier this year. However, the FDA’s decision in March to have the drug undergo scrutiny by an independent advisory committee came as a surprise. But Dr. Daniel Skovronsky, chief scientific officer at Lilly, expressed satisfaction with the committee’s unanimous vote, viewing it as a validation of his 25-year effort to treat Alzheimer’s.

The FDA will now complete its review of trial data and make a final decision on approval.

The drug is based on a new theory about how Alzheimer’s develops and spreads through the human brain. The theory, which is gaining traction among medical researchers, posits that Alzheimer’s begins when rough, hard plaques of a protein called amyloid pile up in the brain. These amyloid plaques then ultimately lead to the death of neurons.

Donanemab works by attacking amyloid plaques in patients with early-stage Alzheimer’s. According to a press release from Eli Lilly, in Phase III trials of the drug last year, “Among all participants, treatment with donanemab reduced amyloid plaque on average by 84 percent at 18 months, compared with a 1 percent decrease for participants on placebo.”

Importantly, as Eli Lilly also relayed, “Participants were able to stop taking donanemab once they achieved pre-defined criteria of amyloid plaque clearance.” While many treatments for various diseases on the market today require patients to continue a drug regimen indefinitely, patients prescribed donanemab can come off it as soon as their amyloid plaque build-ups are eliminated. In the Eli Lilly study, “Approximately half of participants met this threshold at 12 months and approximately seven of every ten participants reached it at 18 months.”

Those results seem to represent an astonishing breakthrough in treatment of Alzheimer’s. While the drug hasn’t shown evidence of outright curing the disease, it does appear to dramatically slow the progression of Alzheimer’s symptoms. As The New York Times has reported, in a 76-week-long study of 1,736 patients with Alzheimer’s, “cognitive decline slowed by about 4.5 to 7.5 months in those taking donanemab compared with those who got the placebo.” Meanwhile, nearly half who took donanemab remained at the same cognitive level one year later, compared with 29 percent who got the placebo.

On average, patients with Alzheimer’s live four to eight years after their diagnosis. This new treatment could significantly extend that timeline and give patients with the disease a much higher quality of life.

Donanemab is unique in its use of monoclonal antibody technology. Monoclonal antibodies are specially crafted proteins made in labs to act like the body’s natural defense system, targeting specific harmful substances. They are designed to latch onto specific molecules, such as those found on viruses or cancer cells, marking them for destruction or directly neutralizing them.

In diseases like Alzheimer’s, these antibodies can attach to and help remove harmful proteins like amyloid that build up in the brain, potentially slowing the disease’s progress. Essentially, monoclonal antibodies are like precision-guided missiles that seek out the substances that doctors believe cause Alzheimer’s.

However, like all drugs, donanemab does come with some concerns, as the FDA panel noted. In trials, three patients on donanemab died from “brain swelling or bleeding.” Upon review, the three deaths were attributed to other factors, but the panel nonetheless noted the risk.

Dean Follmann, a member of the FDA panel and statistician at the National Institutes of Health, told NPR that the evidence that donanemab works is “very strong.” Though it won’t cure Alzheimer’s, Follmann said, it will slow progression of the disease enough to be “meaningful to patients.”

If donanemab proves successful, it might also lead to more breakthroughs using monoclonal antibodies. It may well be that someday soon, this debilitating disease which afflicts nearly one in nine seniors could have a permanent cure.

Andrew Shirley is a veteran speechwriter and AMAC Newsline columnist. His commentary can be found on X at @AA_Shirley.