FDA committee votes in favor of donanemab for early Alzheimer’s

Panel is unanimous on questions of effectiveness, benefits vs. risks

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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An advisory committee to the U.S. Food and Drug Administration (FDA) has unanimously voted in favor of donanemab, an anti-amyloid therapy developed by Eli Lilly that’s currently up for approval as a treatment for early Alzheimer’s disease.

All members of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted yes to the question: “Do the available data show that donanemab is effective for the treatment of Alzheimer’s disease in the population enrolled in the clinical trials with mild cognitive impairment and mild dementia?”

The committee also gave a unanimous “yes” to a separate question asking whether the benefits of donanemab outweigh the therapy’s risk in Alzheimer’s patients who have mild cognitive impairment or mild dementia.

The vote was welcomed by advocates in the Alzheimer’s community. “A future with more approved Alzheimer’s treatments is a tremendous advancement for people eligible for these drugs. Progress with treatment is happening,” Joanne Pike, president and CEO of the Alzheimer’s Association, said in an association press release.

“If approved, donanemab will expand the first class of disease-modifying drugs, serving as the building blocks for future generations of drugs,” Howard Fillit, MD, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said in a statement from the foundation.

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Approval review had been delayed

A decision on donanemab’s approval was initially expected by the end of 2023. The FDA took the unexpected step of asking for an advisory committee meeting, delaying the application’s review. The FDA isn’t bound to abide by recommendations from its advisory committees, but it almost always does.

Lilly’s application for donanemab is mainly based on data from the Phase 3 TRAILBLAZER-ALZ 2 clinical trial (NCT04437511). The study tested donanemab against a placebo in more than 1,100 people with early Alzheimer’s. Results showed patients given donanemab had less decline on multiple cognitive and functional measurements after 18 months, with particularly pronounced effects among patients who were younger and had less impairment at the study’s start.

Donanemab is designed to target amyloid-beta, a protein that forms toxic clumps in the brain that are thought to drive Alzheimer’s. This mechanism is similar to that of Leqembi (lecanemab), an anti-amyloid therapy that last year became the first Alzheimer’s treatment to win full FDA approval.

With the positive committee vote, donanemab is poised to become the second anti-amyloid medicine to win full FDA approval for Alzheimer’s. Both therapies are known to cause as a common side effect amyloid-related imaging abnormalities (ARIA), which are marked by swelling or bleeding in the brain. Most cases of ARIA related to anti-amyloid therapies are not serious, though the side effect can be fatal in severe instances.

Although advocates welcomed the promise of a second anti-amyloid therapy, they also emphasized a need to develop additional treatments that can target other biological mechanisms that drive Alzheimer’s.

“Today’s vote offers hope that donanemab will be approved in the coming months, but it’s important to look at this milestone in the larger treatment landscape for Alzheimer’s, which will entail a combination therapy and precision medicine approach,” Fillit said. “Anti-amyloids are not a silver bullet, but they offer opportunities for patients to modify the course of the disease while the field works towards developing more novel therapies that target the underlying biology,” he added.

The Alzheimer’s Association’s Pike pointed to the need for “more types of treatments, targeting a variety of aspects of the disease, with greater efficacy and safety,” which she said “will lead to possibilities for combination therapies that address the complexity of the disease.”

“We look forward to more treatment options, and novel therapies that target other aspects of the disease, including lifestyle and behavioral-based interventions,” said Maria C. Carrillo, PhD, chief science officer and medical affairs lead of the Alzheimer’s Association.