The Food and Drug Administration (FDA) approved this week the third amyloid-targeting drug treatment for Alzheimer’s Disease: donanemab-azbt, an intravenous antibody infusion being marketed by Eli Lilly as Kisunla.
FDA’s decision is in line with the agency’s independent advisory committee, who voted unanimously last month that the clinical trial data demonstrated the treatment's efficacy.
In a pivotal clinical trial involving 1,736 participants, Alzheimer’s disease progressed 22% more slowly in those given donanemab compared with those given a placebo. Participants earlier in the disease course with low or medium levels of another brain protein called tau had a greater response: their disease progressed 35% more slowly compared to placebo.
Donanemab is intended for patients with mild cognitive impairment or the mild dementia stage of disease who have confirmed amyloid pathology, which is assessed via lumbar punctures or PET scans. Donanemab is a monoclonal antibody that reduces the accumulation of amyloid beta plaques in the brain, which are associated with the disease. Donanemab joins Eisai and Biogens’ lecanemab (Leqembi) on the market, which was approved in January 2023. The first-approved antibody treatment, aducanumab, was taken off the market due to concerns over efficacy and safety.
Donanemab is the first treatment with evidence supporting its discontinuation after patients’ brains are clear of amyloid plaques. Clinical trial data showed that 47% of participants taking donanemab had visually negative amyloid PET scans at 12 months, and 69% had negative scans at 18 months. Furthermore, its intravenous infusions are given every four weeks (as opposed to every two weeks with lecanemab).
“These medications have given us hope and they’ve given our families hope,” Elizabeth J. Santos, M.D., M.P.H., president-elect of the American Association for Geriatric Psychiatry told Psychiatric News Alert. Santos, who is also the clinical chief of the Division of Geriatric Mental Health and Memory Care at the University of Rochester, was not involved in the development of Kisunla.
Santos added, however, the FDA guidance leaves open the question about how to obtain the needed amyloid-confirming PET scans to determine when to discontinue donanemab. Amyloid-assessing PET scans are largely unavailable in non-research settings and scarcely ever covered by insurance.
As with lecanemab, the drug carries a boxed warning on the risk of amyloid-related imaging abnormalities (ARIA), which may in rare cases cause serious and life-threatening intracerebral hemorrhages or focal neurologic deficits that can mimic ischemic stroke.
The approval came just days after the Alzheimer’s Association Workgroup issued revised criteria for the diagnosis and staging of Alzheimer’s disease that calls for the use of biomarkers and a revised disease staging system.
“Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine — including cancer, heart disease and diabetes — and is becoming a unifying concept common to all neurodegenerative diseases,” said lead author Clifford Jack, Jr., M.D., a professor of radiology at the Mayo Clinic in Rochester, Minn., in a news release. “An unchanging principle is that effective treatment will always rely on the ability to diagnose and stage the biology driving the disease process.”
For more information, see the Psychiatric News article “Donanemab May Slow Alzheimer’s Progression”
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