fda alert

FDA Converts Alzheimer Disease Treatment to Traditional Approval

Leigh Precopio

Following the results of a recent confirmatory clinical trial, the FDA converted the use of lecanemab-irmb for the treatment of adult patients with Alzheimer disease to a traditional approval. It was initially approved for use in January 2023 under the accelerated approval pathway.

Lecanemab reduces amyloid plaques, which is a key pathophysiological aspect of Alzheimer disease in the brain. This approval is the first amyloid beta-directed antibody to be converted to a traditional approval for Alzheimer disease treatment.

The Study 301 (CLARITY AD) phase 3 randomized controlled trial was conducted to verify clinical benefit of lecanemab. The researchers included a total of 1795 adults with Alzheimer disease and either mild cognitive impairment or mild dementia stage of disease, as well as confirmed amyloid beta pathology. Patients were randomized to receive lecanemab 10mg/kg once every two weeks or placebo.

When compared with placebo, the treatment group had statistically significant and clinically meaningful reduction of decline from baseline to 18 months on the Clinical Dementia Rating Scale Sum of Boxes score, which was the primary endpoint. Similar results were observed for the secondary endpoints, including the Alzheimer Disease Assessment Scale Cognitive Subscale 14 and the Alzheimer Disease Cooperative Study—Activities of Daily Living Scale for Mild Cognitive Impairment.

Common adverse effects observed include headache, infusion-related reactions, and amyloid-related imaging abnormalities (ARIA), which is a known complication of antibodies targeting amyloid, and commonly presents as temporary brain swelling on imaging studies and possible small spots of bleeding in or on the brain. Headache, confusion, dizziness, vision changes, and nausea have all been associated with ARIA, although adverse effects due to ARIA are not common. Brain edema, associated seizures and other severe neurological symptoms, and intracerebral hemorrhages have been infrequently reported with this class of medication.

Individuals using lecanemab who are homozygous for the ApoE ε4 allele have a higher incidence of ARIA and associated severe adverse events when compared with heterozygotes and noncarriers. Testing for ApoE ε4 allele should be performed before starting lecanemab. Additionally, the use of anticoagulation medication was associated with a higher number of intracerebral hemorrhages.

Of note, lecanemab has only been examined in those with mild cognitive impairment or mild dementia stage of disease. Lecanemab use in earlier and later stages of the disease was not studied.


FDA converts novel alzheimer’s disease treatment to traditional approval. News release. The US Food and Drug Administration; July 6, 2023. Accessed July 24, 2023.