Lecanemab (Leqembi) for Alzheimer's: Real-World Data and Treatment Update 2026

What Is Lecanemab and How Does It Work?

Lecanemab (brand name Leqembi), developed by Eisai and Biogen, is a humanized IgG1 monoclonal antibody that selectively binds to soluble amyloid-beta (Aβ) protofibrils — large, toxic aggregates of amyloid protein believed to play a central role in Alzheimer's disease pathology. Unlike some earlier anti-amyloid therapies that primarily targeted insoluble amyloid plaques, lecanemab's preferential binding to protofibrils is thought to address the most neurotoxic forms of amyloid. The drug is administered as an intravenous infusion every two weeks at a dose of 10 mg/kg body weight.

The pivotal CLARITY AD trial (Study 301), published in the New England Journal of Medicine in January 2023, enrolled 1,795 participants aged 50-90 with early symptomatic Alzheimer's disease (mild cognitive impairment or mild dementia due to Alzheimer's) who had confirmed amyloid pathology on PET scan or CSF biomarkers. After 18 months, lecanemab reduced the rate of cognitive and functional decline by 27% compared to placebo as measured by the CDR-SB (Clinical Dementia Rating — Sum of Boxes) scale. Amyloid PET imaging confirmed substantial reduction in brain amyloid burden, with 68% of lecanemab-treated participants achieving amyloid-negative status.

The FDA granted lecanemab traditional (full) approval in July 2023, making it the first anti-amyloid therapy to receive this designation based on demonstrated clinical benefit. This approval was significant because it triggered Medicare coverage, enabling broader access for eligible patients. CMS covers lecanemab under Coverage with Evidence Development (CED), requiring enrollment in a qualifying registry to collect real-world outcomes data.

What Are the Risks and Side Effects of Lecanemab?

Amyloid-related imaging abnormalities (ARIA) represent the most significant safety concern with lecanemab and other anti-amyloid therapies. In the CLARITY AD trial, ARIA-E (edema/effusions, representing vasogenic edema on MRI) occurred in 12.6% of lecanemab-treated participants versus 1.7% on placebo. ARIA-H (hemosiderin deposition, representing microhemorrhages or superficial siderosis) occurred in 17.3% vs. 9.0%, respectively. Most ARIA events were asymptomatic and detected only through routine MRI surveillance. Symptomatic ARIA occurred in approximately 3% of treated participants, presenting as headache, confusion, dizziness, visual disturbances, or nausea.

APOE ε4 carriers, particularly homozygotes, face a substantially higher risk of ARIA. In CLARITY AD, ARIA-E occurred in approximately 33% of APOE ε4 homozygotes compared to 6% of non-carriers. Current prescribing guidelines recommend APOE genotyping before initiating therapy, and the FDA label includes a boxed warning about ARIA risk. Patients on anticoagulant therapy are generally excluded from treatment due to the risk of ARIA-related hemorrhage. Routine MRI monitoring is required — typically before treatment initiation, before the 5th, 7th, and 14th infusions, and as clinically indicated.

Infusion-related reactions occurred in approximately 26% of lecanemab-treated participants, mostly mild to moderate (fever, flu-like symptoms, nausea, headache). These were most common with the first infusion and generally decreased with subsequent treatments. Three deaths during the CLARITY AD trial and its open-label extension were potentially associated with ARIA complications, underscoring the importance of careful patient selection and monitoring.

How Does Lecanemab Compare to Donanemab?

Donanemab (brand name Kisunla), developed by Eli Lilly, received FDA approval in July 2024 based on the TRAILBLAZER-ALZ 2 trial. This trial enrolled 1,736 participants with early symptomatic Alzheimer's and demonstrated a 35% slowing of clinical decline on the iADRS (integrated Alzheimer's Disease Rating Scale) in the combined population, and 36% in participants with low-to-medium baseline tau pathology. Donanemab showed rapid amyloid clearance, with approximately 80% of participants achieving amyloid-negative status by 12 months, compared to 68% for lecanemab at 18 months.

A key difference between the two drugs is the treatment paradigm. Donanemab is designed as a time-limited therapy: once a patient achieves amyloid clearance (confirmed by PET scan), treatment can be discontinued. In TRAILBLAZER-ALZ 2, approximately 52% of participants completed treatment by 12 months and 72% by 18 months. Lecanemab, by contrast, is currently administered as a continuous biweekly infusion, though ongoing studies are evaluating maintenance dosing schedules and a subcutaneous formulation for improved convenience. Donanemab is given as a monthly intravenous infusion (720 mg for the first three doses, then 1400 mg monthly).

ARIA rates were somewhat higher with donanemab: ARIA-E occurred in 24.0% of participants (vs. 12.6% for lecanemab), and serious ARIA events were also more frequent. Three deaths in the donanemab trial were associated with ARIA. Head-to-head trials comparing the two therapies have not been conducted, and direct comparison of efficacy is limited by differences in trial design, patient populations, and outcome measures. Treatment decisions should be individualized based on patient characteristics, APOE genotype, comorbidities, and practical considerations such as infusion frequency and monitoring requirements.