The European Medicines Agency (EMA) has approved Leqembi (lecanemab) for the treatment of early Alzheimer's disease, a significant step forward in addressing cognitive decline associated with the condition. This decision follows a re-examination of an earlier decision where the EMA had initially rejected the drug due to concerns over potential side effects. The approval offers new hope for millions affected by Alzheimer's, particularly those in the early stages of the disease.
Clinical Trial Evidence
Leqembi's approval was influenced by compelling clinical trial evidence. Patients who received the treatment showed lesser cognitive decline compared to those who were administered a placebo, as measured by the Clinical Dementia Rating-Sum of Boxes (CDR-SB). The data from 1,521 patients with one or no copy of the ApoE4 gene showed that, after 18 months of treatment, patients treated with lecanemab had a smaller increase in CDR-SB score than those who received placebo (1.22 versus 1.75), indicating slower cognitive decline.
Restricted Patient Population
The EMA has specified that Leqembi will only be available to certain groups—namely, patients with mild symptoms and those with little to no copies of the ApoE4 gene, a known risk factor for Alzheimer's disease. Individuals with two copies of this gene may face hazardous side effects, including possible cerebral swelling or hemorrhage, ruling them out from being eligible for Leqembi under the current approval. In patients treated with lecanemab, 8.9 percent of those with only one or no copy of ApoE4 experienced ARIA-Edema, compared with 12.6 percent of all patients; 12.9 percent of patients in the restricted population experienced ARIA-Haemorrhage, compared with 16.9 percent of the broader population.
Safety Measures and Monitoring
The EMA recommendation comes with a number of provisos, including the implementation of risk minimization measures to reduce the risk of severe and symptomatic ARIA. Patients will require MRI scans to monitor for ARIA prior to initiating treatment and before the fifth, seventh, and 14th dose. Additional MRI scans may be needed during treatment if patients develop symptoms of ARIA. The company will provide a guide and checklist for healthcare professionals, an alert card for patients, and training programmes on ARIA for healthcare professionals. In addition, it must carry out a post-authorization safety study to further characterize ARIA-E and ARIA-H and assess the effectiveness of the risk minimization measures.
Implications for Healthcare
With the roll-out of Leqembi, healthcare providers will have to adopt new strategies for patient monitoring and education, explaining its benefits alongside the potential risks, thereby fostering informed decision-making among patients and their families. The HSE National Dementia Office (NDO) has been preparing for the possible introduction of DMTs for AD. Aside from the cost of DMTs, considerations for health systems include the structures required to identify patients, deliver the drug, and monitor patients. The emergence of DMTs for early AD is widely regarded as a significant breakthrough and may also act as a lever to drive enhancements of diagnostic and care pathways.
