2024-11-14 17:15:00
The European Medicines Agency Ema thinks again and says yes to the anti-Alzheimer therapy lecanemab (Leqembi*). “After having re-examined its initial negative opinion, the Committee for Medicinal Products for Human Use (CHMP) – informs the EU regulatory body in a note – recommended granting a marketing authorization for Leqembi, to treat mild cognitive impairment (memory and thinking problems) or mild dementia due to Alzheimer’s disease (early Alzheimer’s disease) in patients who have only one or no copies of ApoE4, a certain form of the gene for protein apolipoprotein E”. The review therefore concluded that the benefits outweigh the risks in a limited patient population.
How and to whom it is administered
Leqembi is part of the family of monoclonal antibodies that target beta amyloid, an abnormal protein that is deposited in the brains of Alzheimer’s patients. The drug will be available through a controlled access program to ensure it is only used in the recommended patient population. The choice to give the green light for a limited population is linked to the fact that “patients with only one or no copies of ApoE4, compared to people with two copies of ApoE4, are less likely to experience a recognized serious side effect with the drug , i.e. Amyloid-related imaging abnormalities (Aria), involving swelling and potential bleeding in the brain CHMP concluded that, in the restricted population evaluated in the review, the benefits of Leqembi in slowing the progression of disease symptoms are greater. of its risks.
In July 2024 the negative opinion
In July 2024, the Committee had issued a negative opinion on the use of the drug in a broader population of all patients with early Alzheimer’s disease. But in light of data showing a lower risk of Aria in some patients, he changed the outcome of the evaluation. Aria occurs in two forms: Aria-E (edema) which involves the accumulation of fluid in the brain and Aria-H (hemorrhage) which involves small hemorrhages in the brain. This problem can occur naturally in all Alzheimer’s patients, but is exacerbated by taking medications such as Leqembi.
In the review requested by the company, the CHMP considered subgroup analyzes that excluded data from patients who carried 2 copies of the ApoE4 gene and who were therefore at higher risk of Aria. The results of these analyzes showed that among patients treated with Leqembi, 8.9% of those with only one or no copies of ApoE4 experienced Aria-E, compared to 12.6% of all patients; similarly, 12.9% of patients in the restricted population experienced Aria-H compared to 16.9% in the broader population. Among patients treated with placebo, the rates were 1.3% and 6.8% for Aria-E and Aria-H, respectively, in the restricted population.
In terms of efficacy, the benefits of lecanemab in the restricted population are in line with those observed in the broader population. For the review, the company provided a subgroup analysis of data from the main study, which included 1,521 patients with one or no copies of ApoE4 out of a total of 1,795 patients. The main measure of effectiveness was a change in cognitive and functional symptoms after 18 months, measured using a dementia rating scale known as Cdr-Sb. After 18 months of treatment, patients treated with Leqembi had a smaller increase in Cdr-Sb score than those who received placebo (1.22 versus 1.75), indicating slower cognitive decline.
The CHMP recommended as a condition that risk minimization measures are in place to reduce the risk of severe and symptomatic Aria and monitor its long-term consequences. Patients will have to undergo MRI (magnetic resonance imaging) scans to monitor Aria before starting treatment and before the fifth, seventh and 14th doses. Additional MRI scans may be needed at any time during treatment if patients develop symptoms such as headache, confusion, vision changes, dizziness, nausea and difficulty walking. To raise awareness of this side effect and ensure early diagnosis and treatment, the company will provide a guide and checklist for healthcare professionals, an alert card for patients and training programs for healthcare professionals.
Furthermore, it must conduct a post-authorisation safety study to further characterize the issue and evaluate the effectiveness of risk minimization measures. The company will establish an EU-wide registry study with patients treated with Leqembi. The registry study can also be used to gather information on patients’ progression to the later stages of Alzheimer’s and possible long-term consequences of Aria. What will be the next steps now? The CHMP opinion “is an intermediate step in Leqembi’s path towards patient access – recalls the EMA - The opinion will now be sent to the European Commission for the adoption of a decision on a wide marketing authorization Once granted, decisions on price and reimbursement will take place at the level of each Member State, taking into account the potential role and use of this medicine in the context of its national healthcare system.”
How does lecanemab compare to traditional Alzheimer’s therapies in terms of effectiveness?
Interview between Time.news Editor and Alzheimer’s Research Expert Dr. Maria Germani
Time.news Editor: Welcome, Dr. Germani! We are thrilled to have you with us today to discuss an important development in Alzheimer’s treatment, specifically regarding the newly reviewed therapy, lecanemab—marketed as Leqembi. Can you start by explaining the significance of the recent decision by the European Medicines Agency (EMA)?
Dr. Maria Germani: Thank you for having me! The EMA’s decision to grant marketing authorization for lecanemab is a significant milestone in the fight against Alzheimer’s disease. This therapy is designed for patients experiencing mild cognitive impairment or mild dementia associated with early-stage Alzheimer’s, particularly for those with one or no copies of the ApoE4 gene, which is linked to a higher risk of Alzheimer’s. The review reflected a reassessment of the risks versus benefits, particularly for this targeted patient population.
Time.news Editor: That’s fascinating! So, what makes lecanemab unique compared to other Alzheimer’s treatments?
Dr. Maria Germani: Lecanemab is part of a class of drugs known as monoclonal antibodies, which specifically target beta-amyloid—a protein that accumulates in the brains of Alzheimer’s patients. By reducing beta-amyloid plaques, lecanemab aims to slow cognitive decline, a goal that traditional treatments haven’t achieved effectively. This therapy’s focused approval for a limited population also emphasizes a more personalized approach to treatment, which is very promising.
Time.news Editor: Interesting! You mentioned the associated risks, particularly the side effects linked to amyloid-related imaging abnormalities (Aria). Can you elaborate on those risks and why the EMA chose to limit access to specific patients?
Dr. Maria Germani: Absolutely! Aria can manifest in two forms: Aria-E, which involves brain swelling, and Aria-H, linked to small brain hemorrhages. These side effects can be exacerbated in patients with two copies of the ApoE4 gene. The EMA’s decision to limit lecanemab to those with one or no copies is based on studies showing that this group has a significantly lower incidence of these adverse effects. The data indicated, for example, that 8.9% of individuals in the targeted group experienced Aria-E compared to 12.6% in the broader patient population.
Time.news Editor: It sounds like a careful balance is being struck between efficacy and safety. Can you tell us about the clinical results that support lecanemab’s effectiveness?
Dr. Maria Germani: Certainly! In clinical trials involving this restricted patient population, lecanemab demonstrated a meaningful reduction in the rate of cognitive decline compared to a placebo. After 18 months, those treated with lecanemab had a lower increase in dementia rating scores, indicating a slower progression of symptoms. This suggests that the drug not only has potential benefits in halting cognitive decline but also confirms its efficacy aligns with what was observed in a broader population earlier.
Time.news Editor: Given this recent development and approval, what are the next steps for both healthcare providers and patients?
Dr. Maria Germani: The next steps involve implementing controlled access programs to ensure the drug is used within the identified patient population safely. Health care providers will need to be educated on the criteria for prescribing lecanemab, monitor patients closely for potential side effects, and ensure that robust risk-minimization strategies are in place. For patients and their families, ongoing discussions with healthcare teams about the potential benefits and risks will be crucial in making informed decisions about their treatment options.
Time.news Editor: Thank you, Dr. Germani, for clarifying these complex issues surrounding lecanemab. This therapy could represent a turning point in Alzheimer’s treatment, and it’s important for our audience to stay informed.
Dr. Maria Germani: Thank you for the opportunity to discuss this important topic. It’s an exciting time in Alzheimer’s research, and I hope that therapies like lecanemab offer hope to those affected by this challenging condition.
