A New Era in Alzheimer's Treatment: Approved Amyloid Antibodies
For decades, treatments for Alzheimer's disease (AD) only addressed symptoms without altering the disease's course [1.2.1]. The landscape shifted dramatically with the development of monoclonal antibodies that target amyloid-beta (Aβ) plaques, a key pathological hallmark of AD [1.3.1]. These therapies are designed to remove these toxic protein clumps from the brain, thereby slowing cognitive and functional decline in patients with early-stage disease [1.9.1]. As of September 2025, two such drugs have received full FDA approval and are in clinical use, representing a significant breakthrough in managing this neurodegenerative condition [1.2.1, 1.2.3].
Currently Approved Amyloid-Beta Directed Antibodies
The FDA has granted full approval to two treatments in this class:
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Lecanemab (Leqembi®): Developed by Eisai and Biogen, Leqembi received full FDA approval in July 2023 [1.2.1, 1.3.2]. It is indicated for patients with mild cognitive impairment (MCI) or mild dementia stage of Alzheimer's disease [1.3.3]. The therapy works by targeting and neutralizing soluble Aβ aggregates called protofibrils before they form plaques, and also helps remove existing plaques [1.3.3, 1.3.5]. In its pivotal Clarity AD clinical trial, Leqembi demonstrated a 27% slowing of clinical decline on the global cognitive and functional scale (CDR-SB) over 18 months compared to a placebo [1.3.3, 1.3.5]. It is administered as an intravenous (IV) infusion every two weeks [1.3.3].
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Donanemab (Kisunla™): Developed by Eli Lilly, Kisunla gained full FDA approval in July 2024 [1.4.2, 1.4.3]. Like Leqembi, it is for patients in the early symptomatic stages of AD with confirmed amyloid pathology [1.4.6]. Donanemab specifically targets established amyloid plaques for removal [1.8.2]. A key feature of its treatment regimen is that patients may be able to stop the monthly infusions if they achieve a prespecified level of amyloid plaque clearance, which can occur in as little as 6 to 12 months for many patients [1.8.2, 1.8.5]. Clinical trials showed it slowed cognitive and functional decline by up to 39% in certain patient populations [1.2.5].
The Story of Aducanumab (Aduhelm®)
Aducanumab (Aduhelm®) was the first amyloid-targeting antibody to receive FDA approval in June 2021, via the accelerated approval pathway [1.5.4, 1.5.1]. This approval was highly controversial due to conflicting clinical trial data regarding its efficacy in slowing cognitive decline, despite its proven ability to reduce amyloid plaques [1.5.2, 1.5.3]. Due to the controversy, lack of compelling efficacy data, and subsequent refusal by Medicare and other insurers to cover its high cost outside of clinical trials, the drug saw very limited use [1.5.1]. In early 2024, Biogen announced it was discontinuing the development and commercialization of Aduhelm to focus resources on Leqembi [1.5.1].
Comparison of FDA-Approved Amyloid Antibodies
| Feature | Lecanemab (Leqembi®) | Donanemab (Kisunla™) |
|---|---|---|
| FDA Full Approval | July 2023 [1.3.2] | July 2024 [1.4.2] |
| Mechanism | Targets soluble Aβ protofibrils and insoluble plaques [1.3.3] | Targets deposited Aβ plaques for clearance [1.8.2] |
| Administration | Intravenous infusion every 2 weeks [1.3.3] | Intravenous infusion every 4 weeks [1.2.6] |
| Treatment Duration | Ongoing, with potential for reduced frequency after 18 months [1.3.3] | Finite; may be stopped once amyloid clearance is achieved [1.8.2] |
| Efficacy (Slowing Decline) | 27% over 18 months vs. placebo (CDR-SB) [1.3.5] | Up to 39% vs. placebo (iADRS) [1.2.5] |
| Annual Cost (Approx.) | $26,500 [1.6.4] | $32,000 [1.8.4] |
Patient Eligibility and Safety Considerations
Treatment with these antibodies is not for everyone. Patients must be in the early stages of Alzheimer's—mild cognitive impairment or mild dementia—and have biomarker confirmation of amyloid plaques in the brain via PET scan or cerebrospinal fluid (CSF) analysis [1.9.1, 1.9.5].
Exclusion criteria are strict and can include:
- Patients in moderate or severe stages of AD [1.9.1].
- Evidence of other dementias (e.g., Lewy body, vascular) [1.9.1].
- Certain findings on a baseline brain MRI, such as more than four microhemorrhages or evidence of superficial siderosis [1.9.2, 1.9.5].
- Use of anticoagulant medications, due to bleeding risks [1.9.5].
The most significant safety concern for this class of drugs is Amyloid-Related Imaging Abnormalities (ARIA), which involves temporary brain swelling (ARIA-E) or microhemorrhages (ARIA-H) [1.3.1, 1.7.2]. While often asymptomatic and detected on routine monitoring MRIs, ARIA can, in rare cases, be serious or even fatal [1.3.1, 1.7.3]. The risk of ARIA is significantly higher in individuals who are homozygous carriers of the APOE4 gene, a known genetic risk factor for Alzheimer's [1.3.3, 1.9.5]. For this reason, APOE genotyping is recommended before starting treatment to inform the risk-benefit discussion [1.9.5].
Conclusion
The full FDA approval of lecanemab (Leqembi) and donanemab (Kisunla) marks a pivotal advancement in Alzheimer's therapy, offering the first treatments proven to modify the underlying disease process [1.2.1]. While not a cure, they represent a crucial step forward by modestly slowing cognitive decline in eligible patients. The journey of these drugs, including the withdrawal of aducanumab, underscores the complexities of developing effective and safe treatments. The decision to pursue this therapy requires careful consideration of the potential benefits against the significant risks, particularly ARIA, and involves a thorough evaluation, genetic testing, and ongoing monitoring with a neurology specialist [1.9.5].
For further information on clinical trials, you may visit ClinicalTrials.gov.
