The U.S. Food and Drug Administration (FDA) has given traditional approval to lecanemab, marketed as Leqembi, for the treatment of early-stage Alzheimer’s disease. This development represents a step in addressing the underlying biology of the condition. The medication is intended for individuals experiencing mild cognitive impairment or mild dementia caused by Alzheimer’s. Lecanemab’s approval followed clinical trials that demonstrated its ability to change the course of the disease for patients in the initial phases, offering a treatment that targets the disease process itself rather than just managing symptoms.
Lecanemab’s Mechanism of Action
Alzheimer’s disease is characterized by the accumulation of a protein called amyloid-beta in the brain, which forms sticky clumps known as plaques that disrupt communication between brain cells. The formation of these plaques begins with smaller, soluble clusters of amyloid-beta called protofibrils, which are considered highly toxic to neurons. Lecanemab is a lab-engineered monoclonal antibody designed to specifically target and bind to these harmful protofibrils.
By attaching to the protofibrils, lecanemab marks them for removal by the brain’s immune cells, known as microglia. The antibody has a high affinity for these protofibrils, binding to them with greater selectivity than to mature amyloid plaques. This targeted action helps clear the protofibrils from the brain, aiming to interrupt the disease process before extensive neuronal damage occurs.
Clinical Trial Findings
Lecanemab’s approval was based on the CLARITY AD clinical trial, a global study of 1,795 participants with early Alzheimer’s disease. The primary goal was to measure the drug’s effect on the rate of cognitive and functional decline. Over 18 months, lecanemab slowed this decline by 27% compared to a placebo, as measured by the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale. This scale assesses cognitive abilities and practical functions like memory, orientation, and personal care.
This degree of slowing could translate to a person retaining the ability to manage personal finances or participate in hobbies for a longer period. The trial also met its secondary endpoints, showing a reduction in amyloid plaque burden in the brain. The results also showed a 37% slowing of decline in activities of daily living. This suggests an impact on a patient’s ability to function independently.
Patient Eligibility and Administration
Treatment with lecanemab is not for everyone with Alzheimer’s disease. The medication is indicated for patients in the early stages of the disease, including those with mild cognitive impairment (MCI) or mild dementia. A requirement for eligibility is the confirmed presence of amyloid-beta pathology in the brain. This confirmation must be obtained through either a positron emission tomography (PET) scan or an analysis of cerebrospinal fluid (CSF) collected via a lumbar puncture.
Patients who meet these criteria receive the drug through an intravenous (IV) infusion once every two weeks in a clinical setting, such as a hospital or an infusion center. Each session lasts about one hour. After an initial treatment phase of approximately 18 months, some patients may transition to a less frequent maintenance dosing schedule of one infusion every four weeks, a decision made in consultation with their doctor.
Associated Side Effects and Safety Profile
The use of lecanemab is associated with a risk known as amyloid-related imaging abnormalities (ARIA), which prompted the FDA to include a boxed warning on the drug’s label. ARIA involves brain changes visible on MRI scans and is categorized into two types: ARIA-E (brain swelling) and ARIA-H (microhemorrhages or superficial bleeding). While often asymptomatic, ARIA can cause symptoms such as headache, confusion, dizziness, and vision changes.
Due to this risk, regular monitoring with MRI scans is required before starting treatment and at several points during the initial months of therapy. The risk of developing ARIA is higher in individuals who carry two copies of the apolipoprotein E ε4 (ApoE4) gene variant, a known genetic risk factor for Alzheimer’s. Other potential side effects include infusion-related reactions, such as fever, chills, and nausea.
The Broader Landscape of Alzheimer’s Treatments
Lecanemab’s approval marks a point in the evolution of Alzheimer’s therapies, particularly among drugs that target amyloid-beta. It follows the earlier approval of aducanumab (Aduhelm), but lecanemab’s clinical trial data provided more definitive evidence of slowing cognitive decline, leading to its traditional FDA approval. Aducanumab was later voluntarily withdrawn from the market by its manufacturer.
The field continues to advance, with other amyloid-targeting drugs like donanemab also demonstrating positive results in clinical trials and gaining regulatory approval. Donanemab functions by targeting established amyloid plaques for removal. The development of these medications signifies a shift in the therapeutic strategy for Alzheimer’s, focusing on early intervention to alter the disease’s progression.