BELGIUM – In a significant policy shift, the European Medicines Agency (EMA) has reversed its initial rejection of Biogen and Eisai’s Alzheimer’s drug, Leqembi (lecanemab).
The agency now recommends the therapy’s approval for a select group of patients after reconsidering its stance in response to new data and stakeholder feedback. The final decision on marketing authorization is expected in January 2025.
In July 2024, the EMA’s Committee for Medicinal Products for Human Use (CHMP) issued a negative opinion on Leqembi.
The decision was based on concerns about amyloid-related imaging abnormalities (ARIA), a potential side effect causing brain swelling or bleeding visible on MRI scans.
The committee argued that the drug’s modest effect in slowing cognitive decline did not outweigh the risks for patients with early Alzheimer’s.
New analysis narrows patient group
However, following a re-examination requested by Eisai, the CHMP has now endorsed Leqembi for patients with mild cognitive impairment or mild dementia due to Alzheimer’s disease, provided they carry only one or no copies of the ApoE4 gene variant.
Patients with two copies of ApoE4 are at a higher risk of ARIA and are excluded from the recommended group.
The decision was driven by subgroup analyses showing reduced ARIA risks in the restricted population.
Among patients with one or no copies of ApoE4, 8.9% experienced ARIA-related brain swelling (ARIA-E) and 12.9% had brain bleeding (ARIA-H).
By contrast, in the broader patient group, these rates were higher at 12.6% and 16.9%, respectively.
Cognitive benefit demonstrated
The subgroup analyses also showed that Leqembi slowed cognitive decline over 18 months compared to a placebo.
Patients treated with Leqembi had a CDR-SB score increase of 1.22, indicating less impairment, versus 1.75 for the placebo group.
In addition to clinical data, the EMA acknowledged input from patients, caregivers, clinicians, and advocacy organizations.
According to the agency, these stakeholders highlighted the unmet need for treatments targeting Alzheimer’s-related cognitive decline despite associated risks.
Controlled access and monitoring
To address safety concerns, the EMA has mandated a controlled access program for Leqembi. Patients will undergo MRI scans before starting treatment and prior to the fifth, seventh, and 14th doses to monitor for ARIA. Additional scans will be required if symptoms develop during treatment.
Leqembi’s global trajectory
Leqembi targets amyloid plaques in the brain, a hallmark of Alzheimer’s disease linked to cognitive impairment.
It received accelerated approval from the U.S. FDA in January 2023, followed by full approval in July 2023.
Despite these approvals, Eisai recently lowered its sales forecast for Leqembi to US $280 million, citing delays in U.S. revenue.
In the third quarter of 2024, the drug generated US $67 million globally, including US $39 million from the U.S.
A subcutaneous version of Leqembi, currently administered via intravenous infusion, is expected to drive higher adoption.
The EMA’s decision aligns with similar restrictions adopted by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), which also limited Leqembi’s use based on ApoE4 status.
If approved by the EMA, Leqembi’s entry into the European market could bolster its global impact, offering a new treatment option for carefully selected Alzheimer’s patients while addressing safety concerns through stringent monitoring protocols.
