Alzheimer’s disease affects millions of older adults and is expected to nearly double in prevalence by 2060, posing a growing public health challenge1. Recent advances have introduced new monoclonal antibody drugs that target amyloid-beta plaques, a key factor in Alzheimer’s pathology, offering hope to slow cognitive decline in early-stage patients23. These therapies, including Leqembi and donanemab, represent the first disease-modifying treatments approved to slow progression rather than just manage symptoms34. However, they come with significant risks and limitations, emphasizing the need for careful patient selection and monitoring5.
Leqembi vs. Donanemab: A Comparison
Leqembi (lecanemab) and donanemab are monoclonal antibodies designed to target amyloid-beta plaques in the brain, which are believed to contribute to neurodegeneration in Alzheimer’s disease62. Both drugs work by reducing the accumulation of these plaques, thereby slowing the progression of cognitive decline in patients with early symptomatic Alzheimer’s or mild cognitive impairment (MCI) due to Alzheimer’s23. However, they differ in their specific mechanisms, dosing schedules, and safety profiles.
“This is the biggest effect that's ever been seen in an Alzheimer's trial for a disease-modifying drug.”
— Daniel Skrovonsky, Eli Lilly8
Leqembi targets soluble aggregated amyloid-beta species and is administered via intravenous infusion every two weeks7. Donanemab binds to deposited amyloid plaques and is given every four weeks intravenously7. Clinical trials have shown that donanemab slowed cognitive decline by approximately 35%, while lecanemab reduced decline by about 27%, marking the largest effect seen to date for disease-modifying Alzheimer’s drugs87. Despite this, neither drug reverses existing neuronal damage3.
Both therapies carry risks of amyloid-related imaging abnormalities (ARIA), which include brain swelling (ARIA-E) and microhemorrhages (ARIA-H)910. Donanemab has been associated with higher rates of ARIA, with up to 30.5% of patients showing brain abnormalities in trials compared to 17.3% for lecanemab91057. Symptoms related to ARIA can include headache, nausea, and confusion, and in rare cases, fatal adverse events have been reported9108. The presence of the APOE ε4 gene increases the risk of ARIA, necessitating regular MRI monitoring during treatment74.
| Drug | Administration | Target | Main Side Effects | Trial Population | Real-World Eligibility (%) |
|---|---|---|---|---|---|
| Leqembi | IV infusion every 2 weeks | Soluble aggregated amyloid-beta | Brain swelling, microbleeds (ARIA) | Early AD, MCI | ~8% |
| Donanemab | IV infusion every 4 weeks | Deposited amyloid plaques | Higher ARIA rates, some deaths | Early AD, MCI | Not directly compared |
Clinical trials for both drugs have primarily enrolled patients with early-stage Alzheimer’s or MCI confirmed by amyloid pathology210. There are no head-to-head trials directly comparing the two drugs, making definitive conclusions about superiority difficult102. Additionally, both drugs require extensive cognitive assessments, PET scans, and genetic testing for APOE ε4 to determine eligibility and monitor safety5.
The trials have also underrepresented minority populations, including Black and Hispanic Americans, who face higher dementia risks but remain disproportionately excluded from research1213. This lack of diversity limits understanding of how these drugs perform across different populations and underscores the need for more inclusive clinical studies1213.
Accessibility and Rollout of New Alzheimer's Drugs
The introduction of Leqembi and donanemab marks a significant milestone in Alzheimer’s treatment, but their rollout faces several challenges related to patient eligibility, safety monitoring, and healthcare infrastructure2311. Both drugs are approved primarily for early-stage Alzheimer’s disease, including mild cognitive impairment due to AD, and require confirmation of amyloid pathology before initiation210.
Early and precise diagnosis is critical to identify patients who may benefit from anti-amyloid therapies. Specialized clinics with multidisciplinary teams can help fast-track treatment while managing risks14.
Strict inclusion and exclusion criteria used in clinical trials limit real-world eligibility. Many patients with cardiovascular comorbidities, prior strokes, or uncontrolled hypertension are excluded from treatment due to increased risk of adverse events112. As a result, only a small fraction of early AD patients qualify for these therapies in practice—approximately 8% for lecanemab, with donanemab’s real-world eligibility not yet fully established112.
The drugs require intravenous infusions every two to four weeks and frequent magnetic resonance imaging (MRI) to monitor for ARIA and other side effects214. This necessitates specialized clinical settings with multidisciplinary teams capable of managing complex diagnostic and safety protocols.
To address these challenges, the University of Kansas Alzheimer’s Disease Research Center developed a specialized clinic model, the KU Anti-Amyloid Treatment Clinic (KU-AATC), to streamline patient evaluation, treatment, and monitoring14. This clinic includes neurologists, nurse practitioners trained in dementia, infusion teams, neuropsychologists, and care navigators working together to expedite access and ensure safety14.
💡 Did You Know? Anti-amyloid therapies may slow disease progression but carry serious risks including brain bleeds and stroke-like symptoms, requiring close monitoring during treatment5.
Key features of the KU-AATC model include:
- Rapid and condensed diagnostic testing to identify eligible patients quickly14
- Multidisciplinary team management to handle treatment complexities and safety monitoring14
- Regular MRI scans to detect and manage ARIA early14
- Coordination with insurers for prior authorizations and treatment approvals14
- Focus on treating patients with mild symptoms to maximize benefit14
The model aims to be scalable and adaptable for other healthcare systems to meet the growing demand for these new therapies14.
Despite these advances, the high cost of treatment—estimated at $26,500 to $34,000 annually per patient—poses additional barriers to widespread access15. Furthermore, ongoing research is needed to develop treatments for moderate to severe Alzheimer’s stages and to improve inclusivity in clinical trials1213.
- Eligibility limited by strict trial-based criteria excluding many with cardiovascular disease or uncontrolled hypertension112
- Need for extensive diagnostic testing including PET scans, cognitive assessments, and APOE ε4 genotyping52
- Requirement for intravenous infusions every 2–4 weeks with ongoing MRI monitoring for ARIA214
- Underrepresentation of minority populations in trials limits understanding of safety and efficacy across diverse groups1213
- High treatment costs may restrict access and insurance coverage15
