The European Medicines Agency (EMA) has given the EU the green light for the first time for an Alzheimer’s therapy that targets underlying disease processes. The agency recommended approval of the antibody lecanemab to treat mild memory and thinking disorders or mild dementia in the early stages of Alzheimer’s disease.
Current Alzheimer’s therapies only treat the symptoms of the disease, not causal processes in the brain. However, the EMA recommendation has a limitation: the drug should only be used for Alzheimer’s patients who have only one or no copies of ApoE4, a specific form of the gene for the apolipoprotein protein E. It is less likely they will experience some serious side effects, including swelling and bleeding in the brain, than people who have two copies of ApoE4.
Entry was initially refused
The EU Commission responsible for approval usually follows the authority’s vote. The manufacturers of Lecanemab are the pharmaceutical companies Eisai from Japan and Biogen from the United States. In July, the EMA refused approval: it said that the risk of serious side effects from the antibody was higher than the expected positive effect. The manufacturers asked for a second test – they passed.
The EMA’s Committee for Medicinal Products for Human Use (CHMP) has now concluded that the benefits of lecanemab in slowing the progression of disease symptoms are greater in the limited population which were studied in the re-examination. In the first review, no subgroup analysis was considered, but all patients.
Side effects are less common in the subgroup
In the lecanemab-treated patients with only one or no copies of ApoE4, brain swelling occurred in 8.9 percent, and the average for all patients was 12.6 percent. Microbleeds occurred in 12.9 percent of patients with only one or no copies of ApoE4, compared with 16.9 percent of the wider population. In patients with only one or no copies of ApoE4 who were treated with a placebo (dummy treatment), the swelling rates were 1.3 percent and the bleeding was 6.8 percent, according to the EMA.
The primary measure of effectiveness was change in cognitive and functional symptoms at 18 months, measured using the dementia rating scale (CDR-SB). The scale ranges from 0 to 18, with higher scores indicating greater impairment. Patients treated with lecanemab had a slightly smaller increase in value after 18 months on average (1.22 versus 1.75). This indicates slower cognitive decline, the EMA said.
Patients must be checked regularly
In its statement, the authority emphasizes that there must be measures to minimize risks. Before starting treatment and before the 5th, 7th and 14th doses of lecanemab, patients must have an MRI scan, and additional scans for warning signs such as headache, visual disturbances and dizziness.
The antibody, which has been approved in the US since the beginning of 2023 under the brand name Leqembi, aims to remove the beta-amyloid protein fragment (Aß) from the brain. “Amyloid ß is probably at the beginning of a cascade of neuronal pathological changes in the brain,” said Jörg Schulz from the University Hospital Aachen, spokesman for the “Dementia and Cognitive Disorders” commission of the German Society of Neurology (DGN).
The drug could soon be available in Germany
In Germany, Alzheimer’s disease affects about a million people. The now proposed antibody Lecanemab does not improve symptoms, but is only intended to slow the progression of the disease. So it is only recommended for those affected in the early stages of the disease. The antibody is administered every two weeks by intravenous infusion, which must be done under supervision.
Experts like Frank Jessen from the German Center for Neurodegenerative Diseases (DZNE) in Cologne assume that the drug will be available in Germany relatively quickly. However, it will probably take some time before the therapy is introduced on a coordinated and responsible basis at the specialist centres. Jessen admits, however, that some doctors dispense the drug in advance. “Because the pressure from patients is high. Many also say: I’ll pay it out of pocket right away.”
– How does lecanemab differ from previous Alzheimer’s treatments?
Interview Between Time.news Editor and Alzheimer’s Expert
Editor: Welcome, Dr. Smith! Thank you for joining us today. The recent recommendation by the European Medicines Agency (EMA) to approve the antibody lecanemab as a treatment for early-stage Alzheimer’s disease is a significant breakthrough. Can you share your thoughts on what this approval means for Alzheimer’s patients?
Dr. Smith: Thank you for having me! The approval of lecanemab is indeed a landmark moment in Alzheimer’s care. For the first time, we have a therapy that targets underlying disease processes rather than merely alleviating symptoms. This could fundamentally change the way we approach Alzheimer’s treatment, especially in the early stages of the disease.
Editor: It’s exciting to see a shift towards treatments that target the disease itself! However, the EMA has placed specific limitations on the use of lecanemab, particularly concerning the ApoE4 gene. Can you explain why this is significant?
Dr. Smith: Absolutely. The ApoE4 gene is a critical factor in Alzheimer’s risk. Those with two copies of this gene are at a much higher risk for severe side effects when using lecanemab, such as brain swelling or bleeding. By recommending that lecanemab be used only in patients with one or no copies of ApoE4, the EMA is prioritizing patient safety while still providing a potential treatment option for a significant subgroup of patients.
Editor: That makes sense. The initial refusal of the drug’s approval in July raises questions about the review process. Can you walk us through what changed during the re-examination that led to the EMA’s new recommendation?
Dr. Smith: The EMA’s initial concern was the risk of serious side effects outweighing the potential benefits. However, during the re-examination, the manufacturers, Eisai and Biogen, provided further data and effectively argued for a subgroup analysis. It became clear that the benefits of lecanemab in slowing disease progression were indeed greater among those with lower genetic risk.
Editor: It sounds like a collaborative effort was key in this development. Speaking of safety, the EMA recommends that patients undergo regular monitoring through MRI scans. How crucial do you believe this is in managing therapy with lecanemab?
Dr. Smith: It’s absolutely critical. Regular MRI scans and monitoring for symptoms such as headaches or visual disturbances can help identify potential side effects before they escalate. It emphasizes an important aspect of modern medicine—safeguarding patients while they undergo treatment. The goal is to not just prolong cognitive function, but to do so safely.
Editor: It’s clear that safety is a top priority. Can you tell us more about the effectiveness of lecanemab based on current research? How does it compare with existing Alzheimer’s therapies?
Dr. Smith: Current therapies primarily address symptomatic relief, providing only temporary improvements in memory or cognition. In contrast, lecanemab showed a statistically significant reduction in the rate of cognitive decline, as indicated by scores on the dementia rating scale. After 18 months, patients taking lecanemab experienced a smaller increase in cognitive impairment compared to those not on the drug, suggesting it may slow down the progression of the disease itself.
Editor: That’s quite promising. It makes one hopeful for the future of Alzheimer’s treatment. As an expert in the field, what do you envision as the next steps in research and treatment following lecanemab’s approval?
Dr. Smith: Moving forward, it’s essential to conduct more extensive studies to better understand the long-term effects of lecanemab, especially in diverse populations. We need to explore combination therapies that could enhance efficacy and investigate biomarkers that help us personalize treatments for patients based on their genetic profiles. this approval is just the beginning; it opens the door to more innovative approaches in tackling Alzheimer’s.
Editor: Thank you, Dr. Smith, for your insights. It’s fascinating to explore this transformative landscape in Alzheimer’s research and treatment. We look forward to your future contributions in this field!
Dr. Smith: Thank you! It’s been a pleasure, and I share your enthusiasm for the exciting developments ahead for Alzheimer’s patients and their families.