The European Medicines Agency’s (EMA) human medicines committee (CHMP) has reversed its initial stance and recommended granting marketing authorization for Leqembi (lecanemab) to treat early Alzheimer’s disease in a restricted patient population. The drug is approved for those with mild cognitive impairment or mild dementia due to Alzheimer’s disease who have one or no copies of the ApoE4 gene, which is linked to an increased risk of amyloid-related imaging abnormalities (ARIA).
ARIA Risk Reduction in Target Population
ARIA, a serious side effect of Leqembi involving brain swelling (ARIA-E) or small brain bleeds (ARIA-H), is exacerbated by anti-amyloid beta antibodies like Leqembi. Patients with two copies of the ApoE4 gene are at higher risk of ARIA, and this subgroup was excluded from the re-evaluation.
Data showed that 8.9% of patients with one or no ApoE4 copies experienced ARIA-E, compared to 12.6% in the broader population. Similarly, 12.9% experienced ARIA-H, compared to 16.9% in the broader group. Among placebo-treated patients, ARIA rates in the restricted population were 1.3% for ARIA-E and 6.8% for ARIA-H.
Effectiveness Demonstrated in Subgroup Analysis
The CHMP re-assessed data from 1,521 patients with one or no ApoE4 copies, out of a study cohort of 1,795. Results showed that patients receiving Leqembi had a slower progression of cognitive decline, as measured by the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB). After 18 months, the Leqembi group’s CDR-SB scores increased by 1.22 points versus 1.75 points in the placebo group, indicating a notable delay in symptom progression.
Safety and Risk Management Measures
To mitigate ARIA risks, the EMA recommends regular MRI scans at critical treatment points and additional scans if symptoms like headaches or confusion emerge. A controlled access programme will limit Leqembi’s use to the recommended patient population. The manufacturer is also required to:
- Provide training and tools for healthcare professionals.
- Distribute patient alert cards and guides.
- Conduct post-authorization safety studies, including an EU-wide registry to monitor long-term safety and effectiveness.
Next Steps
As per the press release, the CHMP’s positive opinion will now be forwarded to the European Commission for a final decision on marketing authorization. Pricing and reimbursement decisions will follow at the national level in EU member states.
This decision reflects input from patients, caregivers, and clinicians, acknowledging the urgent need for effective Alzheimer’s treatments while addressing safety concerns.