EMA to Review New Safety Data on Alzheimer’s Drug Leqembi

The European Medicines Agency (EMA) announced it will review new safety data on the Alzheimer’s disease drug Leqembi (lecanemab). This follows a prior decision to recommend its use in the European Union.

Lecanemab is indicated for treating mild cognitive impairment and early Alzheimer’s disease. It is intended for patients with one or no copy of the apolipoprotein epsilon 4 (APOE4) gene variant. The monoclonal antibody binds to aggregated soluble and insoluble forms of amyloid beta, removing plaques and preventing further buildup.

EMA’s Changing Stance

In November 2024, the EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended marketing granting a marketing authorization for Leqembi. This overturned its initial rejection in July 2024, when the committee determined that the drug’s risks outweighed its benefits. Concerns centered on heightened incidence of amyloid-related imaging abnormalities (ARIA). These involve ARIA-E (edema) and ARIA-H (hemorrhage).

These side effects are more common in patients treated with amyloid-targeting antibody drugs such as lecanemab. Individuals with two copies of the APOE4 gene are at the highest risk for ARIA.

Reexamination Led to Approval

A subsequent reexamination of clinical evidence persuaded the CHMP to reverse its decision. The analysis excluded patients with two copies of the APOE4 gene and found that lecanemab’s benefits in this restricted cohort aligned with those observed in the broader population.

As a result of that review, a marketing authorization was recommended for patients with one or no copies of APOE4, provided that risk minimization measures were in place to reduce the risk for severe and symptomatic ARIA and that patients were monitored for long-term consequences.

European Commission Calls for Further Review

The European Commission has since asked the CHMP to consider new safety information on Leqembi that it said became available only since the recommendation was made in November, “and whether this may require an update of the opinion.” Details of the new safety information were not specified.

The commission has also requested reconsideration of whether risk minimization measures specified by the committee are clear enough to ensure they can be properly implemented.

The CHMP is due to review the data and address the commission’s request when it meets in February.

Peter Russell has been a journalist for 40 years covering international news, health, medicine, and national politics on radio, TV, and online. He is based in the UK.