Lecanemab is a medication for individuals in the early stages of Alzheimer’s disease. It aims to address underlying biological changes and offers a new approach for managing the disease’s progression.
What Lecanemab Is and How It Works
Lecanemab is a monoclonal antibody engineered to target and bind to amyloid beta protein in the brain. Amyloid beta is a protein fragment that clumps together to form plaques, a hallmark of Alzheimer’s disease.
The drug targets soluble amyloid beta protofibrils, intermediate forms believed to harm neurons and contribute to cognitive decline. By binding to these protofibrils, lecanemab helps clear them from the brain, a process involving the brain’s immune cells like microglia. Reducing these aggregates aims to prevent larger plaque formation and lessen their impact on brain function.
Who Is Lecanemab For
Lecanemab is for individuals with a confirmed diagnosis of early Alzheimer’s disease, including mild cognitive impairment or mild Alzheimer’s dementia. Before treatment, biomarker testing, such as amyloid PET scans or cerebrospinal fluid analysis, must confirm amyloid pathology in the brain.
Genetic testing for the APOE-ε4 gene is recommended before therapy. Individuals with one or two copies of the APOE-ε4 allele have an increased risk of amyloid-related imaging abnormalities (ARIA), a potential side effect. Those with two copies (APOE-ε4 homozygotes) face a higher incidence of ARIA, including symptomatic and serious cases. Discussing these risks helps inform treatment decisions.
Treatment Administration and Potential Side Effects
Lecanemab is administered as an intravenous infusion, typically given every two weeks. Each infusion takes about an hour. Patients require regular monitoring, including periodic brain MRI scans, to check for potential side effects.
The most common side effects include infusion-related reactions, which can occur in about one in four patients. These reactions are generally mild to moderate and may present as fever, chills, flushing, or changes in blood pressure; pre-medication can help prevent them. Another potential side effect is amyloid-related imaging abnormalities (ARIA), which can involve ARIA-E (edema or brain swelling) and ARIA-H (hemorrhage or bleeding in the brain). ARIA-E occurred in about 13% of patients, with most cases being asymptomatic, but some symptomatic cases can include headaches or confusion. ARIA-H occurred in about 17-18% of patients, and while largely asymptomatic, serious cases of intracerebral hemorrhage, some fatal, have been observed with this class of medications.
Lecanemab treatment is not recommended for individuals who are taking strong blood thinners, such as warfarin or rivaroxaban, because these medications increase the risk of hemorrhage. Careful consideration is advised for patients with factors indicating an increased risk for intracerebral hemorrhage. Clinicians should also consider if symptoms resembling an ischemic stroke might be due to ARIA-E before administering thrombolytic therapy.
Understanding Lecanemab’s Impact
Lecanemab does not offer a cure for Alzheimer’s disease; rather, it works to slow the progression of cognitive decline. Clinical trials have shown that lecanemab can reduce cognitive and functional decline. In a large Phase 3 clinical trial, lecanemab treatment reduced clinical decline on a global cognitive and functional scale (CDR-SB) by approximately 27% over 18 months compared to a placebo.
This modest efficacy in slowing cognitive decline was observed as early as six months into treatment and continued across all measured time points. The drug’s ability to reduce amyloid beta plaque in the brain is associated with these observed clinical benefits. While lecanemab represents an advancement in treating early Alzheimer’s, it is important for patients and their families to have realistic expectations about its ability to modify the disease course.