European Regulators Diverge on Alzheimer's Drug Approvals as Italy Halts Reimbursement
核心洞察
Italy's drug agency AIFA (搜索) has decided not to reimburse lecanemab and donanemab, two anti-amyloid monoclonal antibodies for early Alzheimer's disease, despite their approval by US FDA and European Medicines Agency.
Switzerland approved only one of the two drugs, with Eisai withdrawing its lecanemab application due to restrictive conditions that would limit the eligible patient population.
The regulatory decisions highlight the complex balance between modest clinical benefits and serious safety risks, with different countries reaching varying conclusions on patient access.
Italy's medicines agency AIFA (搜索) has decided against reimbursing two groundbreaking Alzheimer's drugs, while Switzerland approved only one of the treatments, highlighting the complex regulatory landscape facing the first therapies to slow cognitive decline in decades.
AIFA (搜索)'s technical-scientific director Pierluigi Russo announced the preliminary decision on social media, stating that "deciding not to reimburse a medicine is sometimes a terribly complex decision." The two monoclonal antibodies - lecanemab (developed by Eisai-Biogen) and donanemab (developed by Lilly (搜索)) - had been approved by both the US FDA and European Medicines Agency but failed to gain reimbursement approval from Italy's Scientific and Economic Commission for Medicines.
Regulatory Challenges Across Europe
The Italian decision reflects broader challenges facing European regulators as they weigh the modest benefits of these treatments against their significant costs and safety risks. Each drug costs approximately €26,000 per year per patient, according to AIFA (搜索) officials.
Patrizia Spadin, president of the Italian Alzheimer's Association, criticized the decision, stating: "However small the number of patients eligible for treatment, the possibility of benefit is denied to people who are thus condemned to live the full drama of Alzheimer's disease. Access would remain reserved for those who can pay privately for the entire costly course of treatment, confirming that Alzheimer's is a disease for the rich."
In Switzerland, the regulatory outcome proved equally complex. Swissmedic (搜索) approved Kisunla (donanemab) on January 22, 2025, but Eisai withdrew its application for Leqembi (lecanemab) on January 29, citing disagreement with "restrictive" conditions that would have created a "substantially smaller eligible patient population in Switzerland" than in the rest of Europe.
Clinical Efficacy and Safety Concerns
Both drugs represent significant advances in Alzheimer's treatment, being the first to slow cognitive decline while addressing amyloid plaques in the brain. In pivotal clinical trials, lecanemab slowed cognitive decline by 27% compared to placebo, while donanemab achieved up to 35% reduction in decline rates. However, experts note these benefits may only delay dementia by 4-8 months.
The treatments carry serious safety risks, particularly amyloid-related imaging abnormalities (ARIA) - a potentially life-threatening form of brain swelling and bleeding. Patients carrying the APOE4 (搜索) gene variant, which affects 40-65% of Alzheimer's patients globally, face increased ARIA risks.
Genetic Restrictions and Treatment Access
Swissmedic (搜索)'s assessment concluded that lecanemab should only be approved for patients without any copies of the APOE4 (搜索) gene variant, more restrictive than European approval for patients with one or no copies. For donanemab, Switzerland authorized treatment for patients with no or one copy of the APOE4 variant.
The regulator also suggested limiting lecanemab treatment duration to 18 months, despite the drug being studied as continuous therapy without defined time limits.
Global Regulatory Landscape
The regulatory challenges extend beyond Europe. Germany's healthcare decision-making body determined lecanemab showed no evidence of added benefit compared to current standard care. The Netherlands reached similar conclusions. Australia initially rejected lecanemab twice before approving it in September 2025 with genetic restrictions.
The UK approved both drugs but excluded them from National Health Service coverage due to cost-benefit concerns, limiting access to private patients. In the US, lecanemab carries a list price of $26,500 annually, while donanemab costs $32,000.
Future Implications
Despite regulatory hurdles, these treatments have fundamentally changed perspectives on Alzheimer's disease. Bogdan Draganski, clinical neuroscientist at Bern's Inselspital, noted: "Many people believed that forgetfulness is just a normal part of ageing but now we know we can define the cause and treat it. Leqembi and Kisunla are opening the door to better diagnostics and potentially more effective treatments."
The regulatory decisions underscore the ongoing debate over how to balance hope with scientific evidence in Alzheimer's treatment. With 138 new drugs currently in 182 trials according to recent studies, the field continues to evolve rapidly, though much about the disease remains poorly understood.
For Italy, the final decision awaits board approval on March 25, with AIFA (搜索) noting that "any intermediate negative decisions by the Commission may in any case be subject to subsequent reassessment." In Switzerland, Eli Lilly must still negotiate pricing with federal authorities before Kisunla becomes widely available.