The European Medicines Agency (EMA) has granted approval for Leqembi, a drug developed to slow the progression of Alzheimer's disease. This decision marks a significant advancement in the treatment of early-stage Alzheimer's, offering a new option for patients experiencing cognitive decline. Leqembi, administered via intravenous drip every two weeks, has demonstrated the ability to reduce amyloid plaques, a hallmark of Alzheimer's disease, in clinical trials.
The approval comes with specific restrictions. The EMA recommends Leqembi for patients in the early stages of Alzheimer's disease who have not reached an advanced stage. This decision follows an initial rejection based on concerns that the treatment's benefits did not outweigh the risk of serious side effects, including potential brain bleeding (ARIA - Amyloid Related Imaging Abnormalities). The approval is now limited to individuals with "only one or no copy of the ApoE4 gene," a genetic factor known to increase the risk of Alzheimer's disease and ARIA.
Clinical Considerations and Patient Selection
According to the UK government, approximately 15% of individuals diagnosed with Alzheimer's possess two copies of the ApoE4 gene (homozygous), placing them at a higher risk. Leqembi's approval excludes this group due to the increased risk of brain hemorrhage. The EMA's decision was influenced by subgroup analyses that excluded data from patients carrying two copies of the ApoE4 gene, focusing on those with a more favorable risk profile.
Development and Global Availability
Leqembi, developed by Eisai, a Japanese pharmaceutical company, and Biogen, an American manufacturer, received its initial approval in the United States in January 2023 for patients in the early stages of Alzheimer's. It is also available in Japan, China, and the UK, where it is marketed under the name Lecanemab. In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) approved Lecanemab on August 22, 2024, after a thorough review of its benefits and risks.
Potential Side Effects and Monitoring
Common side effects associated with Lecanemab include infusion-related reactions such as fever and flu-like symptoms, headaches, and ARIA. The EMA highlights that ARIA can manifest as ARIA-E (oedema), involving fluid accumulation in the brain, and ARIA-H (haemorrhage), involving small brain bleeds. While ARIA can occur naturally in Alzheimer's patients, it can be exacerbated by treatments like Leqembi that target amyloid beta.
Expert Perspectives
Mercè Rovira, a neurologist and clinical director at Ace Alzheimer Center in Barcelona, views the EMA's approval as a cautiously optimistic development. She emphasized the importance of this news for continued research and treatment possibilities in the field. Similarly, Hilary Evans-Newton, chief executive of Alzheimer's Research UK, considers Leqembi an important step forward, albeit not a cure, in the way Alzheimer's disease is treated. The EMA has stated that the drug will be made available through a controlled program to ensure it is used only in appropriate patients.
