Eligibility and Safety Considerations for Antiamyloid Alzheimer Therapies

EP: 1.Donanemab Dosing and ARIA Risk in TRAILBLAZER-ALZ 6

EP: 2.Maintaining Efficacy in Safer Donanemab Dosing Regimen

EP: 3.Importance of Patient Selection and Future Therapies in Alzheimer Treatment

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EP: 4.Eligibility and Safety Considerations for Antiamyloid Alzheimer Therapies

At the 2025 Alzheimer’s Association International Conference, held July 27-30, in Toronto, Canada, Alzheimer disease (AD) expert Sharon Cohen, MD, FRCPC, spoke with NeurologyLive^® to discuss the use of emerging AD therapies, specifically focusing on approved antiamyloid antibodies lecanemab (Leqembi; Eisai) and donanemab (Kisulna; Eli Lilly). In this part of the video series, Cohen highlighted key differences between these AD treatments, such as eligibility requirements and safety protocols. She also highlighted amyloid related imaging abnormalities (ARIA) risks and the importance of aligning patient expectations with treatment goals.

In the fourth episode of this AAIC Special Report, Cohen discussed the use of lecanemab and donanemab for early-stage AD. She explained how each antibody targets different forms of amyloid and requires intravenous infusion at specific intervals. Cohen outlined eligibility criteria, including early symptomatic disease, confirmation of amyloid presence, and safety considerations such as pre-treatment MRI scans to assess ARIA risk. She also emphasized the importance of APOE genotyping to guide treatment decisions and the need to individualize therapy based on patient values.

Transcript below edited for clarity.

Sharon Cohen, MD, FRCPC: So it's very exciting that we have 2 antiamyloid treatments now. They're both monoclonal antibodies, and they have approvals not just in North America or in the USA, but in multiple countries now, with more to be added. These are antibodies that target amyloid. They're a little bit different. The class is called antiamyloid monoclonal antibodies, but lecanemab targets primarily protofibril amyloid as well as plaque, whereas donanemab targets primarily plaque-bound amyloid. Both antibodies are given by intravenous infusion—donanemab monthly, lecanemab every 2 weeks.

To be eligible for these treatments, you need to be at an early stage of AD. What does that mean? Symptomatic—either the mild cognitive impairment or mild dementia stage—and you need to have confirmation of amyloid being present in the brain. That can be done either by PET amyloid imaging or CSF, or more recently, some centers are using blood-based biomarkers to confirm amyloid positivity.

Once you have that, that's great, but you're still not quite there, because you need to make sure, from a safety perspective, that things are good to go. What do I mean by that? A pretreatment MRI scan will help rule out non-AD causes, which we're familiar with, but it will also determine whether there is risk for ARIA. ARIA, or amyloid-related imaging abnormality, is the main side effect we worry about with these 2 antibody treatments. If people have a pre-existing burden of cerebral amyloid angiopathy, which is part and parcel of AD—so if they have more than four microbleeds on a pretreatment MRI, evidence of a macrobleed, or evidence of superficial siderosis—this treatment may not be a good one for them, whether lecanemab or donanemab.

So you really need the pretreatment MRI, and you need to know that people will be compliant with MRI monitoring. CAT scans are not enough. If a patient has a pacemaker or other reasons why they can't have an MRI, they are not going to be eligible, even if they have early AD with amyloid confirmed.

What else do you have to consider? APOE genotyping is important. In the US, individuals who are APOE4 homozygotes are allowed to be prescribed lecanemab, but they have a higher risk of ARIA. APOE genotyping allows a robust discussion of risk and benefit. In other regulatory jurisdictions—for example, Europe and the UK—individuals who are APOE4 homozygotes cannot be treated by label with lecanemab or donanemab. So you really must have the ApoE genotyping to determine eligibility, or at least the risk-benefit ratio.

Those are the main things. But there are always discussions about what are patients’ values and expectations? What is their ability to comply? Do they travel a lot or work, which would make biweekly or monthly infusions difficult? Are they snowbirds? There are lots of things to individualize in conversations with patients.