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On June 10, 2024, the U.S. Food and Drug Administration’s Peripheral and Central Nervous System Drugs Advisory Committee gave the nod to donanemab, clearing the way for its marketing approval. All 11 members voted that the antibody was effective for people with mild cognitive impairment or mild dementia due to Alzheimer’s disease, and that its risk-to-benefit ratio was favorable overall. The FDA approved this treatment on July 2, 2024.
By Alzheimer's Prevention Bulletin
A new drug offering further hope to slow or stop the progression of Alzheimer’s disease received approval from the Food and Drug Administration (FDA) on July 2. The drug, donanemab, was given the green light for marketing clearance from the FDA’s Peripheral and Central Nervous System Drug Advisory Committee on June 10. Advisory committees provide independent expert advice to the FDA on broad scientific topics or on certain products to help the agency make sound decisions based on the available science.
Donanemab, developed by Eli Lilly and now branded as Kisunla, offers another approach to Alzheimer's treatment by targeting beta-amyloid plaques in the brain—one of the hallmarks of the disease. These protein deposits are believed to cause cognitive decline and brain cell damage, leading to the debilitating symptoms experienced by Alzheimer's patients.
While the FDA is not bound by the Advisory Committee’s recommendations, it usually will approve a drug after unanimous votes in support of its efficacy and safety, according to Dr. Robert Alexander, Chief Scientific Officer for the Alzheimer’s Prevention Initiative at Banner Alzheimer’s Institute.
The road to developing effective treatments for Alzheimer’s has been long and arduous, but new drug approvals from successful clinical trials offer glimmers of hope.
“This new generation of anti-amyloid antibodies, which includes donanemab, provide a much greater level of amyloid removal from the brain compared to previous anti-amyloid treatments,” said Alexander.
Alexander said there appears to be an amyloid “threshold” and successful drug agents that show an improvement in memory and thinking ability also decrease the level of brain amyloid below this threshold. For example, all positive Phase 2 or 3 trials of anti-amyloid antibodies have shown final centiloid (CL) levels of below 25, with values of 19.5, 24.7 and 23.5 CL for lecanemab, aducanumab, and donanemab, respectively. In contrast, the residual amyloid values in the negative gantenerumab Phase 3 studies ranged from approximately 30-40 CL.
In its Phase 2 clinical study, donanemab demonstrated remarkable efficacy in clearing beta-amyloid plaques, improving cognitive function, and slowing the progression of Alzheimer's. Patients treated with donanemab showed improved memory, attention, and overall cognitive abilities compared to the control group receiving a placebo, providing encouraging evidence of the drug's therapeutic potential.
“I think it is an important advance, although it is not a cure and treated patients continue to decline, albeit at a slower rate,” said Alexander. He said donanemab will initially be approved for the treatment of “early AD,” such as mild cognitive impairment (MCI) and mild Alzheimer’s, but there is another important study that is ongoing called Trailblazer-ALZ 3. The Trailblazer-ALZ 3 trial enrolled participants in with evidence of elevated amyloid but normal memory and thinking ability to see if donanemab can decrease the likelihood of progression to MCI or Alzheimer’s dementia.
“The overall data from the successful anti-amyloid programs is that early intervention yields greater benefit,” said Alexander.
The approval of donanemab also raises hope for the development of combination therapies that can tackle multiple targets, offering even greater potential to slow or halt the disease's advancement.
However, despite this breakthrough, challenges still lay ahead in making donanemab widely accessible to those who need it. Manufacturing, distribution, and affordability will need to be addressed to ensure equitable access to this potentially groundbreaking treatment option.
Alexander said, “I think it is useful for doctors and patients to have options, and the approval of donanemab adds to the number of potentially disease-modifying therapies.” He said donanemab has some advantages relative to lecanemab in that it is administered in a 30-minute infusion every four weeks, versus a one-hour infusion every two weeks for lecanemab.
“Time will tell which antibody is most widely used and a new generation of these potent anti-amyloid antibodies is in development,” Alexander said.
The Alzheimer’s Prevention Registry and its GeneMatch program helped with recruitment for the Trailblazer-ALZ 3 trial and the AHEAD trial of lecanemab. Although both trials are now closed to new enrollment, we are adding new studies on a regular basis. Watch for study opportunity announcements and visit our Find a Study page.
