In November 2024, the European Medicines Agency’s human medicines committee recommended authorisation of Leqembi, or lecanemab, for a selected population with mild cognitive impairment or mild dementia due to Alzheimer’s disease. The recommendation followed a re-examination of an earlier negative opinion.
The change was not simply a reversal. The proposed use was restricted to patients with one or no copies of ApoE4. EMA concluded that this population has a lower risk of amyloid-related imaging abnormalities, or ARIA, which can include brain swelling and bleeding.
What lecanemab does
Lecanemab is a monoclonal antibody designed to bind aggregated forms of beta-amyloid, a protein that accumulates in the brains of people with Alzheimer’s. The aim is to reduce amyloid burden and slow symptom progression during early stages of disease.
The key word is “slow”. Leqembi does not cure Alzheimer’s and does not restore cognitive abilities already lost. Its expected benefit is a reduction in the speed of decline in carefully selected patients diagnosed early.
Why genetic profile matters
ApoE4 is a genetic variant associated with higher Alzheimer’s risk. In the context of lecanemab it also matters for safety. Patients with two copies of ApoE4 have a higher risk of ARIA. The European re-examination therefore narrowed the eligible population to improve the balance between benefit and risk.
This reflects a broader trend in medicine: the same treatment can have a different clinical profile depending on a patient’s genetics. Selection is increasingly based not only on age, symptoms and diagnosis but also biomarkers and genetic variants.
A therapy that depends on diagnostic infrastructure
Using anti-amyloid drugs requires confirmation that a patient actually has amyloid pathology. That can involve specialised imaging or cerebrospinal-fluid analysis, depending on the clinical pathway. ARIA risk also means patients need MRI monitoring.
The real cost of treatment therefore extends beyond the medicine itself. It includes diagnosis, genetics, imaging, specialist staff, infusions and management of adverse events. Health systems introducing a disease-modifying Alzheimer’s therapy need an entire new care pathway.
From general neurology to precision medicine
For decades, Alzheimer’s treatment focused mainly on symptoms. Anti-amyloid therapies represent a different phase, attempting to intervene in the disease’s underlying biology. That approach is scientifically ambitious but operationally more complex.
Clinical benefit must be considered alongside risk. ARIA may be asymptomatic, but in some cases it can be serious. Careful patient selection and structured monitoring are therefore integral to treatment rather than optional additions.
The growing value of early diagnosis
If a therapy is most useful early in disease, the value of timely diagnosis rises. This could accelerate development of blood-based biomarkers, digital cognitive-screening tools and faster referral pathways into specialist care.
Disease-modifying therapies may therefore change how Alzheimer’s is diagnosed. Early diagnosis previously helped mainly with planning and symptom management; when treatment benefit depends on disease stage, time becomes part of therapeutic value.
An important step, not an endpoint
EMA’s re-examination shows how difficult it can be to evaluate innovative medicines when benefits and risks differ across patient subgroups. The answer was not to label the drug universally effective or ineffective, but to restrict use to patients with a more favourable benefit-risk balance.
This model is likely to become more common: advanced drugs, diagnostics and genetics operating as one system. In Alzheimer’s, the next challenge is to scale that system without creating large inequalities in access to testing, specialist centres and treatment.
