A panel of independent advisers to the Food and Drug Administration voted unanimously Monday that the benefits outweigh the risks of the newest experimental Alzheimer’s drug.
Alzheimer’s disease affects more than six million Americans. There is no cure, and there are no treatments or lifestyle modifications that can restore memory loss or reverse cognitive decline.
The drug, made by Eli Lilly, is donanemab. It slightly slowed the cognitive decline of patients in the early stages of the disease, but also presented significant safety risks, including swelling and bleeding in the brain.
The committee concluded, however, that the consequences of Alzheimer’s disease are so dire that even a modest benefit may be worth it.
The FDA generally follows the advice of the agency’s advisory committees, but not always.
The drug is based on a long-standing hypothesis that Alzheimer’s disease begins when hard, rough balls of amyloid, a protein, build up in patients’ brains, followed by a cascade of reactions leading to death of neurons.
The idea is to treat Alzheimer’s disease by attacking amyloid and clearing it from the brain. Two similar drugs for amyloid have been approved recently: Leqembi, made by Eisai and Biogen, was approved last year. The modest risks and benefits of this medication are similar to those of donanemab. Aduhelm, made by Biogen, is the other drug and was approved in 2021, but was abandoned because there was not enough evidence that it could benefit patients.
Donanemab was expected to be approved earlier this year, but in March the FDA decided it would instead require donanemab to undergo scrutiny by an independent advisory committee, a surprise for Eli Lilly.
The vote, said Dr. Daniel Skovronsky, Lilly’s chief scientific officer, confirmed its 25-year quest to find a way to intervene in Alzheimer’s disease. Now, he said, the company is launching a study that it hopes will stop the disease before symptoms even appear.
The debate before the committee Monday concerned some unusual aspects of the donanemab clinical trials, particularly the fact that study participants stopped taking the drug as soon as their amyloid was cleared. Some experts have questioned whether discontinuation is the best strategy and whether clinical practice should include stopping treatment after amyloid clearance.
Donanemab, like Leqembi, is given as intravenous infusions. Alzheimer’s experts said the drugs’ effects on slowing cognitive decline are so modest that they might not be noticeable to patients and their families. Additionally, some pointed out that patients and their families would have no way of knowing how the disease would have progressed without treatment.
Lilly submitted data from a 76-week study of 1,736 people in the early stages of the disease, suffering from either mild cognitive impairment or mild dementia. Participants were randomly assigned to receive donanemab or a placebo. To measure effectiveness, Lilly researchers assessed patients’ performance on cognitive tests.
Cognitive decline
