FDA Advisers Recommend Approval of a New Drug for Early Alzheimer's

Key Takeaways

• Donanemab could be the second amyloid antibody drug approved to treat early-stage Alzheimer's disease.
• The drug slowed cognitive decline by 35 percent compared with placebo, and helped people maintain their daily activities.
• Like its competitor, Leqembi, donanemab comes with a risk of brain bleeding and swelling.

A panel of independent advisers to the U.S. Food and Drug Administration (FDA) has recommended approval of the early-stage Alzheimer's drug donanemab, clearing a key hurdle needed for the medicine to win full FDA approval.

The FDA usually follows the recommendations of its advisory panels, although it isn't required to do so. If donanemab wins full FDA approval, it will be the second medicine, after Leqembi (lecanemab) , that can slow the progression of early-stage Alzheimer's disease by targeting the underlying processes in the brain that lead to this type of cognitive decline.

"The FDA and their advisers are embracing a new era of Alzheimer's disease therapeutics, moving from symptomatic treatments to disease-modifying therapeutics that will hopefully transform Alzheimer's disease from a fatal disease into a chronic disease, as we have done with HIV/AIDS," says Jacobo Mintzer, MD , a psychiatrist at the Ralph H. Johnson VA Healthcare System and a professor at the Medical University of South Carolina in Charleston.

Amyloid Antibodies Clear Brain Plaques Connected to Alzheimer's

Like Leqembi, donanemab is in a family of medicines known as amyloid antibodies, which are designed to clear the brain of plaque deposits that may hasten cognitive decline caused by Alzheimer's disease. Another amyloid antibody, Aduhelm (aducanumab), won conditional FDA approval in 2021 despite an FDA advisory committee recommendation against it; they were concerned about the lack of clear benefits. Aduhelm didn't win full FDA approval, and is being discontinued this year.

In a late-stage clinical trial of 1,182 people with early symptomatic Alzheimer's disease, donanemab slowed cognitive decline by 35 percent compared with a placebo and resulted in 40 percent less decline in activities of daily living like driving, managing finances, and participating in hobbies, according to results published in JAMA .

One safety concern with donanemab is the potential for people who take this drug and other amyloid antibodies to experience what's known as ARIA, or amyloid-related imaging abnormalities. ARIA shows up on brain scans and can sometimes involve seizures or potentially life-threatening brain swelling or bleeding, although many people don't experience symptoms.

Brain Bleeding and Swelling

In the late-stage donanemab trial, 37 percent of people on the drug experienced some type of ARIA with bleeding or swelling in the brain.

ARIA was also seen in a late-stage trial of Leqembi published in the New England Journal of Medicine . This trial found that people taking Leqembi experienced 27 percent slower cognitive decline than people on placebo. It also found that 17 percent of people on lecanemab experienced ARIA with brain bleeding, and 12 percent had ARIA with brain swelling.

Like Leqembi, donanemab will likely win full FDA approval with a requirement that patients get regular magnetic resonance imaging (MRI) scans to look for and address any bleeding or swelling in the brain, says James Galvin, MD, MPH , a professor and the chief of cognitive neurology at the University of Miami Miller School of Medicine in Florida.

"The side effects for all the anti-amyloid antibodies are similar," Dr. Galvin says. In addition to ARIA, another common side effect with these drugs is allergic reactions at the infusion site.

If donanemab wins full FDA approval, part of the decision about which drug to choose may come down to convenience, because donanemab infusions are given every four weeks, while Leqembi is every two weeks, says Sharon Cohen, MD , the medical director of the Toronto Memory Program.

"The benefit of lecanemab and donanemab in slowing progression of Alzheimer's disease is similar and both drugs are appropriate for individuals at early stages of Alzheimer's disease," Dr. Cohen says.

The exact timing of a potential FDA approval decision on donanemab isn't clear right now, according to a spokesperson for Eli Lilly, the drug's developer. Regulators were originally set to make a decision by the first quarter of this year, ending in March, but then decided instead to schedule an advisory panel meeting to review all the data on donanemab, including late-stage trial results.

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Sources

1. Sims J et al. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA . July 17, 2023.
2. van Dyck C et al. Lecanemab in Early Alzheimer's Disease. New England Journal of Medicine . November 29, 2022.