European Commission Greenlights Leqembi, at Last
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On April 15, two years after Eisai requested a marketing license for lecanemab in Europe, the European Commission has greenlit its use. The biologic’s long path included an initial rejection from the European Medicines Agency (EMA), as well as several delays as the application passed through other committees. As a result, Europe lags behind much of the developed world, with lecanemab already approved in 12 other jurisdictions: China, Hong Kong, Israel, Japan, Macao, Mexico, Oman, South Korea, Taiwan, the United Arab Emirates, the U.K., and of course the U.S. Nor is this the end of lecanemab’s European regulatory journey, as responsibility now lies with each individual country to set its own rules on access and reimbursement. Only when this process concludes can patients begin taking the drug.
- The European Commission has approved lecanemab’s marketing application.
- But not for APOE4 homozygotes and people taking anticoagulants.
- Now each European country must set its own rules for access and insurance coverage.
The EC’s approval comes with conditions geared toward minimizing risk. Lecanemab cannot be prescribed to people who have two copies of the APOE4 allele or who are taking anticoagulants. Eisai must offer trainings on how to detect and manage ARIA, the drug’s most dangerous side effect. In addition, Eisai must conduct a post-authorization safety study, including setting up a patient registry for the European Union.
Alzheimer’s researchers in Europe greeted the news with relief. “It is the needed basis for the next steps in AD treatment and care, and it is very important that Europe has made this positive decision,” said Frank Jessen at the German Center of Neurodegenerative Diseases, Köln, who leads the European Alzheimer's Disease Consortium. Philip Scheltens at EQT Life Sciences Dementia Fund agreed. “It would have been unbearable, unacceptable, and quite unrealistic that patients in the EU would have been left in the cold by not having access to Leqembi,” he wrote to Alzforum.
Alzheimer’s researchers in other countries were pleased as well. “It is gratifying to note that the EU has joined the larger community of national governments allowing for standard care, including approved access to medication,” wrote Lawrence Honig at Columbia University, New York City.
Concerns Over Safety
Lecanemab’s European saga began in January 2023, when Eisai and co-sponsor Biogen submitted their application to the EMA. Eighteen months later, in July 2024, the agency’s Committee for Medicinal Products for Human Use (CHMP) recommended rejection, judging that lecanemab’s benefits fell short of its risks, with about one in eight patients developing ARIA.
Alzheimer’s experts at the EADC, as well as the advocacy group Alzheimer Europe, urged Eisai to seek approval for a narrower patient population that excluded APOE4 homozygotes, who have the highest risk. Eisai reanalyzed its Phase 3 data and reported that doing so brought the incidence of ARIA down a quarter while slightly raising the cognitive benefit, for a better overall risk/benefit ratio. The U.K. had approved lecanemab with this restriction in August 2024 (Nov 2024 conference news).
The revised application did the trick. The CHMP reversed itself, recommending approval in November 2024. Still, CHMP required that Eisai provide the drug under a controlled access program to ensure patients meet specified criteria and receive all MRI scans needed to detect and monitor ARIA. In addition to establishing training programs and the post-market safety registry, Eisai must publish a written guide for clinicians, as well as an alert card for patients to let them know what symptoms to report.
Most of the clinician-researchers Alzforum contacted called CHMP’s restrictions reasonable, as they narrow access to those patients most likely to benefit and least likely to suffer harm. “The EU’s balanced approach to moving forward is commendable,” said Nicolas Villain at Sorbonne University, Paris. Wiesje van der Flier at Amsterdam University Medical Center agreed. “Given the novelty of the treatment, controlled access as recommended by EMA is a good thing,” van der Flier wrote to Alzforum. However, she noted that she would prefer access decisions, and the patient registry, lie in the hands of clinicians instead of Eisai. She suggested InRAD, an international AD registry that will start collecting data this year, as an alternative.
Others consider the limits excessive. “We have seen in the U.S. that lecanameb can be used in the real world with the same side effect profile as in the trials. So I hope that the restrictions in the EU will open up in the future to provide treatment to more patients,” Jessen said. Honig called the exclusion of APOE4 homozygotes unfair. Noting that homozygotes comprise about 16 percent of AD patients in Europe, he wants them to be able to decide for themselves whether they want to take the drug. “Risk-aversiveness varies widely among individuals,” Honig noted.
A Winding Road, With Lots of Stop Signs
The EMA’s favorable opinion was not the end of the story. Next, the marketing authorization application went to the European Commission for a decision. In most cases, the EC ratifies the EMA’s approval recommendations. Not this time. The EC referred the application to its Standing Committee. The committee reached an impasse, and, in January 2025, requested more information from CHMP. CHMP reaffirmed its positive opinion, but the standing committee remained deadlocked. This prompted a referral to the Appeal Committee on April 1. That committee also failed to reach consensus. At that point, the EC adopted CHMP’s recommendation, issuing approval April 15.
Several scientists criticized the process as opaque and political. “The approval process of lecanemab in Europe has been long, convoluted, and at times baffling,” said Bart De Strooper at the UK Dementia Research Institute at University College London. “By dragging its feet, the EMA has effectively told Europe’s Alzheimer’s patients that they are second-tier,” he wrote to Alzforum.
Scheltens noted that CHMP does not include Alzheimer’s experts. He decried the fact that some of its members publicly spoke out against the drug before seeing the data. “The EMA decision is more like rolling the dice than the result of a scientifically rigorous process,” Scheltens wrote.
Now Comes the Hard Part—Finances and Logistics
In the next step, decision-making moves to the EU’s 27 member countries, who will each determine their own approval and reimbursement requirements. Scientists said this part of the process may be equally lengthy and complicated. “Pricing negotiations will extend to 2026 in many countries,” Jessen predicted. Villain said that in France, if lecanemab qualifies for an early access program based on the lack of alternative drugs for AD, it could be available within six months. However, if it goes through a standard drug approval process, it could take years. Other countries may move faster or more slowly. “This will create imbalance and inequity among the EU countries,” Scheltens noted.
Just as in the U.S., scientists in Europe foresee challenges for health systems themselves. “Besides the cost of the drug, there are several bottlenecks to the implementation of lecanemab in clinical practice, such as shortage of trained specialists, MRI centers, and full hospital day-care centers,” noted Alberto Lleó at Hospital de la Santa Creu i Sant Pau in Barcelona, Spain. He thinks Spanish clinics are well-positioned to expand these services because of their experience participating in AD trials.
The situation varies by country. “In Finland, while the necessary infrastructure for infusions and monitoring exists, reallocating and prioritizing these resources specifically for memory disorders is needed,” Eino Solje at the University of Eastern Finland, Kuopio, wrote to Alzforum. Villain also noted barriers in France. “Early access is likely to be first restricted to tertiary centers. The current system is not equipped to treat the expected influx of patients, but will adapt as these drugs become available,” Villain said.
For comparison, in the U.K., National Health Service clinics are not offering lecanemab because that country’s NICE agency declined to cover it; that said, AD specialists told Alzforum that the NHS lacks capacity to deliver lecanemab properly even if it were covered. Private services have sprung up, e.g., the Cleveland Clinic London.
Scientists see an upside to the demands now being placed on health systems. Bruno Vellas at the University of Toulouse, France, said lecanemab’s approval will push clinics in the EU to modernize. “[It] will oblige memory centers to upgrade and offer better service to patients to be ready for the new generation of treatments,” Vellas wrote to Alzforum. Solje said the approval marks a major milestone for European Alzheimer’s care. “It will hopefully serve as a powerful incentive for a rapid transition toward biologically based precision diagnostics across the continent,” he wrote.
Beyond these practical concerns, Alzheimer’s experts believe the mere availability of a disease-modifying drug could transform attitudes toward the disease. “It will change the way we look at AD treatment, [shifting] from dementia care to early causal treatment and slowing of disease progression,” Jessen said. Solje considers this change in viewpoint crucial. “We must stop accepting dementia as an ‘inevitable part of aging.’ Instead, we should recognize these conditions as true biological diseases,” Solje wrote.
European scientists are awaiting future treatments, as well. The EU recently turned down a marketing application for donanemab, worrying many that this will become a pattern (Mar 2025 news). Eli Lilly is appealing the decision. “Much work needs to be done to place AD as a health priority in Europe,” Lleó said.
“[The EU’s] conservative stance not only delays patient access to innovation—it sends a discouraging signal to researchers and developers,” De Strooper wrote. “This entire process should serve as a sobering reminder: If Europe wants to lead in science, it must also be willing to act on science.”—Madolyn Bowman Rogers
References
Therapeutics Citations
News Citations
- Leqembi: Side Effects No Worse in Clinical Use Than They Were in Trial
- Donanemab Clinical Use Growing in U.S., Rejected in Europe
External Citations
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Comments
University of Köln
This is very significant. It is important that Europe has made this positive decision, which is the needed basis for the next steps in AD treatment and care.
Lecanemab will enter care in Europe very slowly. This is due to many regulatory aspects, a narrow window of indication, access issues and, of course, reimbursement questions. Pricing negotiation will extend into 2026 in many countries. However, the approval decision will also change the way we look at AD treatment, from dementia care to early causal treatment and slowing of disease progression. This change in perspective is of major relevance.
At least in the beginning, lecanemab is not likely to be widely used. It will initially be provided only in expert centers and, in most countries, only after pricing negotiations. For wider distribution, infrastructural and regulatory requirements will have to be installed and extended, which will take time.
Some expert centers are ready to go with the infusions and MRI monitoring that will be required. But this does not cover all patients. Limitation will most likely exist in infusion capacity and maybe the MR-monitoring.
Regarding the restrictions placed on lecanemab’s use, the EMA is very careful. However, we have seen in the U.S. that lecanemeb can be used in the real world with the same side effect profile as in the trials. So I hope that the restrictions in the EU will open up in the future to provide the treatment to more patients who can potentially benefit.
Alzheimer Center Amsterdam; Head EQT Life Sciences Dementia Fund
I think the approval is really good news, and in fact the only possible outcome, for patients in the EU. It would have been unbearable, unacceptable, and quite unrealistic that patients in the EU would have been left in the cold by not having access to Leqembi.
After the initial rejection of the dossier by CHMP, we, as EU thought leaders, led by Frank Jessen of the EADC, urged the company to resubmit with restrictions on E4 homozygotes and people on oral antithrombotics. In fact, this would leave out those patients with the least chance of benefit and the highest chance of side effects, such as ARIA. We as clinicians felt comfortable with this, and the CHMP in majority agreed with this approach, both in November and again in February.
Whether Leqembi will be widely used will depend mostly on reimbursement. Here the EU suddenly again is split into 27 separate countries that each will make their own decision on the level of reimbursement, perhaps even imposing more restrictions. This will create imbalance and inequity among the EU countries, which is very unfortunate.
Also, system readiness to be able to start treatments will differ hugely among countries, but the main clinics that are members of the EADC have indicated they are able and willing to initiate treatment. As such, I think uptake will be slow but steady, and ongoing gathering and sharing of experiences will guide other clinics to follow.
Of note is the difference in modus operandi between EMA and FDA. The FDA has a staff of neuro-focused experts and convenes an ad hoc advisory panel that consists of expert neurologists and neuroscientists, who are heard in meetings that are open to everyone who wants to follow them. Experts declare any conflict of interest they may have regarding the topic at hand.
EMA has an almost opposite way of working. The Committee for Medicinal Products for Human Use (CHMP) is the European Medicines Agency's (EMA) committee responsible for human medicines. They advise EMA on the potential market authorization. The CHMP consists of scientific experts, usually two of each country. They can be experts in any field of medicine, not necessarily on the matter at hand, in this case (treatment of) Alzheimer’s. The CHMP can ask for advice from a Scientific Advisory Group (SAG) when:
Members of the SAG can consist of experts in neurology, even Alzheimer’s, but as with CHMP, members cannot have any conflict of interest regarding the company or the drug, i.e., have no expertise in the field of clinical trials in Alzheimer’s and cannot have ever worked with any company in this field. Henrik Zetterberg perfectly explained this recently (Zetterberg, 2024). While this may be seen as the ultimate preventive measure against bias, the opposite happens: SAG members are judging the work of scientists who have deep knowledge of the field, trialed by experts with years of experience in performing clinical trials in Alzheimer’s, with a negative bias toward the topic, and in fact toward industry in general. Some of these "experts" do not shy away from voicing their opinion, even before seeing the data, on social media, TV channels, or newspapers. Why is this bias not declared and accepted by EMA as voicing their personal opinion?
In addition, the whole process of assessing the new drug is totally non-transparent: The CHMP and SAG meetings are not open to the public. Based on the above, the EMA decision is more like rolling the dice than the result of a scientifically rigorous process by people who know what they are talking about.
References:
Zetterberg H. Europe sidelines Alzheimer's drug: lessons must be learnt. Nature. 2024 Sep;633(8029):255. PubMed.
Columbia University Vagelos College of Physicians & Surgeons
I am pleased by the European Commission’s decision to authorize lecanemab. It is a reasonably reasonable decision, and will allow at least some patients within the European Union in the early stages of Alzheimer’s disease to receive appropriate care for their condition, including access to this proven-effective disease-modifying treatment.
The full details of the approval, including the stated “strict conditions,” are not evident at this point, but the EC, in their announcement, did specify that their approval did not include use in persons with two copies of the ApoE4 allele. Exclusion of these individuals seems quite unfair: They typically represent about 16 percent of Alzheimer’s-afflicted persons in Europe. Failure to allow them access to this medication means that they and their families cannot make the decision as to whether they would like to receive treatment with this otherwise available therapy. It is difficult to understand why these patients, their families, and their practitioners should not be permitted to weigh, in a shared-decision-making process, as is done in many other jurisdictions throughout the world, the pros and cons, including the increased risk of brain side effects associated with their genotype. Regardless of genotype, irreversible, or even serious, side effects are uncommon, and anti-amyloid antibody therapy is the only proven effective disease-slowing medication. It should be appreciated by all that risk-aversiveness varies widely among individuals.
Nonetheless, despite the EC approval being only “partial,” it is gratifying to note that the EU has joined the larger community of national governments allowing for standard care, including approved access to medication, for at least many persons with Alzheimer disease, a devastating condition for which until recent years there have been no disease course-altering treatments.
Sorbonne University - APHP - Pitié-Salpêtrière Hospital
The EU approval of lecanemab in non-APOE4 homozygotes is excellent news for patients!
The two-year delay between U.S. and E.U. approval of lecanemab highlights the complexities of our multiple-state democracy, where advisory (European Medicines Agency-EMA) and executive (European Commission) roles are distinct. The involvement of multiple commissions, each allowing for appeals, can prolong the process, facilitating diverse opinions and stepwise consensus, particularly when a medicine lacks unanimous approval. Ultimately, this democratic process resulted in EU marketing authorization, a positive outcome for patients, as endorsed by Alzheimer Europe (Alzheimer Europe Welcomes the News That the European Commission Has Authorised Lecanemab for Treatment of Early Alzheimer’s Disease, n.d.).
Lecanemab is not a miracle drug. While its efficacy after 18 months is clearly demonstrated, this efficacy remains modest (Goldberg et al., 2023), and the potential for increased effects over time is still debated (Planche and Villain, 2023; Raket et al., 2024). Side effects are a concern, with Amyloid Related Imaging Abnormality (ARIA) occurring in approximately 21.5 percent of patients, serious adverse events due to ARIA in about 1.1 percent, and deaths linked to ARIA at around 0.3 percent (including at least one case in the open-label extension without apparent confounding factors, Solopova et al., 2023). Treatment burden is also substantial, with bimonthly infusions and ARIA monitoring. Additionally, Alzheimer's disease is undeniably serious. There is notable optimism and pessimism surrounding these drugs, leading to vastly different regulatory decisions worldwide, illustrated by the Australian Therapeutic Goods Administration's refusal.
The European Commission has acted on the EMA's November opinion, granting approval with restrictions for APOE4 homozygotes and those on anticoagulants. This decision includes a mandatory registry to monitor safety, akin to the voluntary initiatives in the U.S. While acknowledging the modest benefits, this approach aims to optimize the risk-benefit ratio by minimizing potential side effects. It determines the risk-benefit ratio to be favorable only for a subset of the trial population.
The exclusion of individuals on anticoagulants aligns with U.S. appropriate use recommendations (Cummings et al., 2023), which note that macrohemorrhage incidence increases approximately fivefold in these patients. However, this exclusion contradicts the FDA's prescribing information, which advises caution. The exclusion of APOE4 homozygotes is primarily due to their sixfold increased risk of ARIA, as well as the greater severity of ARIA observed in these individuals, with severe cases often linked to the APOE4 genotype (Reish et al., 2023; Solopova et al., 2023; Villain et al., 2022). Notably, the two reported deaths associated with serious ARIA involved APOE4 homozygotes (Reish et al., 2023; Solopova et al., 2023). In addition to this safety concern, post hoc analyses indicated that lecanemab's efficacy in APOE4 homozygotes was numerically close to zero, diverging from the clearer benefits seen in heterozygotes and noncarriers (after 18 months of follow-up, the CDR-SB evolution was 1.22 for lecanemab-treated patients compared to 1.75 for the placebo group among 1521 APOE4 heterozygotes and noncarriers) (van Dyck et al., 2023). The effect of lecanemab on the primary outcome for APOE4 homozygotes even appeared to be numerically the opposite of that of heterozygotes and noncarriers (adjusted mean difference on the CDR-SB: +0.28 versus -0.50 and -0.75 for APOE4 heterozygotes and noncarriers, respectively) (van Dyck et al., 2023). While the trial may have been underpowered for assessing efficacy among APOE4 homozygotes, this subgroup was balanced across both treatment and placebo groups (132 versus 136) as part of the CLARITY-AD trial's randomization stratum. The contrasting numerical results in APOE4 homozygotes may simply indicate statistical Type III or IV errors. However, alongside a significant safety signal, these findings raise concerns that necessitate further investigation before authorizing the drug for this subgroup and risking exposure to a potentially ineffective and harmful treatment.
Concerns have been raised that excluding APOE4 homozygotes may lead to genetic discrimination, a serious issue rooted in the tragic 20th-century history of Europe. Current EU regulations against genetic discrimination vary by country. In France, the law enacted on March 4, 2002, strongly reaffirms the prohibition of all genetic discrimination, defining it in the Civil Code and reinforcing it in the Criminal Code as violations of human dignity. Consequently, any distinction made based on genetic characteristics constitutes discrimination, whether for individuals or their associations. The exclusion of APOE4 homozygotes taken by the European Commission cannot be interpreted as a violation of the strong legal framework in place. To address this moral dilemma, an alternative ethical perspective can be considered: Breaking equality does not equate to inequity. As an example, in cancer, genetic testing is often used to determine eligibility for treatment. Another ethical question may arise since this exclusion creates a sense of double punishment, whereby those at greater risk of developing the disease are denied access to treatment. However, it should be highlighted that this decision is driven by an unfavorable risk-benefit ratio of the treatment in this population, not triggered by the genetic status itself. Finally, with this exclusion, important questions also arise regarding follow-up support and research initiatives for this population. The APOLLOE4 trial serves here as an example of proactive engagement in addressing these issues. (Editor’s note: see ALZ-801.)
After obtaining EU marketing authorization, drug approval, availability, and reimbursement shift to the national level, leading to varied timelines across EU member states. In France, an early access procedure (Autorisation d’Accès Précoce–AAP) combines the assessments of the National Agency for Medicines Safety (Agence Nationale de Sécurité du Médicament–ANSM) and the Higher Health Authority (Haute Autorité de Santé–HAS) with a maximum review period of three months (Villain et al., 2022). The agencies evaluate: 1) the treatment's risk/benefit ratio, 2) if it addresses a severe or rare disease, 3) the absence of suitable alternatives, 4) the urgency of treatment implementation, and 5) the presumed innovation of the drug compared to relevant alternatives. If approved via the AAP procedure, the drug becomes available within two months, automatically reimbursed by the French National Health Insurance (Assurance Maladie). A standard application must be submitted within two years after AAP, involving multiple steps: 1) HAS assessment of the medical service provided, 2) economic evaluation by the Commission of Economic Evaluation and Public Health (CEESP), 3) price negotiation with the Economic Committee for Health Products (CEPS), 4) publication of the public price in the Official Journal, and 5) setting the reimbursement rate by the National Union of Health Insurance Funds (UNCAM). Additionally, a ministerial decree on reimbursement is issued. The drug's final registration on the "liste en sus" system, aimed at facilitating access to costly medications in French hospitals, may further delay clinical use. Even in the case of favorable HAS evaluations, this process can take years, particularly for high-cost treatments like lecanemab. Overall, the French system exemplifies the intertwining of medicine access and reimbursement, especially for expensive therapies like mAbs, which are generally fully covered in public hospitals. Thus, drug approval without accompanying reimbursement would likely result in limited practical use within the French healthcare system, where out-of-pocket payment is quite low on average (Or et al., 2023).
Approval through the French early access AAP procedure will define the prescribing conditions for this drug's use, likely limiting prescriptions to specialized tertiary centers, such as the Resource and Research Memory Centers (Centres Mémoire de Ressources et de Recherche–CMRR, 31 centers in France). The standard approval process and price negotiations, which may take years, will also shape the prescribing conditions. Recent French guidelines for lecanemab emphasize the necessity of a comprehensive evaluation of the risk-benefit ratio in multidisciplinary meetings to better inform the shared decision-making process (Villain et al., 2025). To streamline the screening of eligible patients, we also advocate for the use of blood biomarkers with specific cutoffs. The guidelines advise against lecanemab treatment for patients at high risk of amyloid-related hemorrhage, such as those with probable cerebral amyloid angiopathy (Boston criteria v1.5), until more data is available to further improve the risk-benefit ratio. Additionally, MRI monitoring should begin before the third infusion to detect early ARIA associated with lecanemab. A clinical care pathway should be established for managing ARIA, involving trained physicians and radiologists with expertise in neurological emergencies and intensive care to improve the management of ARIA. Finally, a discontinuation protocol based on dementia severity should be implemented after 18 months of lecanemab treatment. These appropriate use recommendations aim to optimize the risk-benefit ratio assessment in potentially eligible patients while facilitating both the short-term and long-term use of lecanemab.
Estimating the number of French patients potentially eligible for lecanemab is challenging, with projections ranging from 66,000 to 1 million (Villain et al., 2022). The implementation of lecanemab within the French healthcare system faces hurdles due to its high cost and therapeutic index. Despite anticipated prescription limitations to specialized centers (see above), the pool of eligible patients may surpass current capabilities for clinical assessment, biomarker testing, infusion, and MRI monitoring. A key factor contributing to inequitable access is the limited availability of specialized diagnostic and infusion centers. Increasing the number of these centers may help reduce disparities. Furthermore, upcoming subcutaneous formulations, anti-amyloid immunotherapies with better safety profiles, titration protocols with improved safety profiles, and plasma biomarkers may enhance eligibility assessment and monitoring, expand indications, and mitigate inequities.
In summary, the EU has approved lecanemab for a selected population based on a favorable risk-benefit ratio, following significant and passionate debate among specialists and the public. This decision does not constitute genetic discrimination. The EMA opted for this course after previously denying marketing authorization for aducanumab and, more recently, donanemab. While dismissing these treatments entirely could deny opportunities for patients with low risk of ARIA, current evidence regarding APOE4 homozygotes indicates both limited efficacy and substantial safety concerns. The EU’s balanced approach to moving forward is commendable.
Next steps involve national-level discussions, particularly in France, which will need to address reimbursement and lengthy price negotiations following potential early access. This early access is likely to be first restricted to tertiary centers, and we recommend thorough risk-benefit analyses for each patient through multidisciplinary meetings before the shared-decision-making process. The current system is not equipped to treat the expected influx of patients, but will adapt as these drugs become available. To expedite negotiations that balance our solidarity system with access to innovation, more long-term and economic studies are needed.
References:
Cummings J, Apostolova L, Rabinovici GD, Atri A, Aisen P, Greenberg S, Hendrix S, Selkoe D, Weiner M, Petersen RC, Salloway S. Lecanemab: Appropriate Use Recommendations. J Prev Alzheimers Dis. 2023;10(3):362-377. PubMed.
Goldberg TE, Lee S, Devanand DP, Schneider LS. Comparison of relative change with effect size metrics in Alzheimer's disease clinical trials. J Neurol Neurosurg Psychiatry. 2023 Dec 14;95(1):2-7. PubMed.
Or Z, Gandré C, Seppänen AV, Hernández-Quevedo C, Webb E, Michel M, Chevreul K. France: Health System Review. Health Syst Transit. 2023 Jul;25(3):1-276. PubMed.
Planche V, Villain N. Advocating for Demonstration of Disease Modification-Have We Been Approaching Clinical Trials in Early Alzheimer Disease Incorrectly?. JAMA Neurol. 2023 Jul 1;80(7):659-660. PubMed.
Raket LL, Cummings J, Moscoso A, Villain N, Schöll M. Scenarios for the long-term efficacy of amyloid-targeting therapies in the context of the natural history of Alzheimer's disease. Alzheimers Dement. 2024 Sep;20(9):6374-6383. Epub 2024 Jul 29 PubMed.
Reish NJ, Jamshidi P, Stamm B, Flanagan ME, Sugg E, Tang M, Donohue KL, McCord M, Krumpelman C, Mesulam MM, Castellani R, Chou SH. Multiple Cerebral Hemorrhages in a Patient Receiving Lecanemab and Treated with t-PA for Stroke. N Engl J Med. 2023 Jan 4; PubMed.
Solopova E, Romero-Fernandez W, Harmsen H, Ventura-Antunes L, Wang E, Shostak A, Maldonado J, Donahue MJ, Schultz D, Coyne TM, Charidimou A, Schrag M. Fatal iatrogenic cerebral β-amyloid-related arteritis in a woman treated with lecanemab for Alzheimer's disease. Nat Commun. 2023 Dec 12;14(1):8220. PubMed.
van Dyck CH, Sabbagh M, Cohen S. Lecanemab in Early Alzheimer's Disease. Reply. N Engl J Med. 2023 Apr 27;388(17):1631-1632. PubMed.
Villain N, Planche V, Levy R. High-clearance anti-amyloid immunotherapies in Alzheimer's disease. Part 1: Meta-analysis and review of efficacy and safety data, and medico-economical aspects. Rev Neurol (Paris). 2022 Dec;178(10):1011-1030. Epub 2022 Sep 29 PubMed.
Villain N, Planche V, Levy R. High-clearance anti-amyloid immunotherapies in Alzheimer's disease. Part 2: putative scenarios and timeline in case of approval, recommendations for use, implementation, and ethical considerations in France. Rev Neurol (Paris). 2022 Dec;178(10):999-1010. Epub 2022 Nov 3 PubMed.
Villain N, Planche V, Lilamand M, Cordonnier C, Soto-Martin M, Mollion H, Bombois S, Delrieu J, French Federation of Memory Clinics Work Group on Anti-Amyloid Immunotherapies. Lecanemab for early Alzheimer's disease: Appropriate use recommendations from the French federation of memory clinics. J Prev Alzheimers Dis. 2025 Apr;12(4):100094. Epub 2025 Feb 25 PubMed.
Scientific Director, Alzheimer Center Amsterdam
The EU approval of Leqembi marks a very significant step. This means that finally, patients, doctors (and researchers (for there are still many questions to be answered) in the EU will also have access to this novel class of medication. An important advance for the entire field.
In my view, market approval of this novel class of medication is like getting your driver’s license. It is only after you get your drivers’ license that you really learn how to drive, by actually doing it in the real world. For these drugs, the field will also learn by doing.
There are so many questions to be answered, for example, what are the long-term effects, who is most likely to benefit, who is least likely to experience side effects, what are optimal dosing schemes. How frequent should maintenance dosing be, or would it even be OK to stop treatment when the brain is cleared of amyloid? Can we use blood markers to initiate treatment, and perhaps in time also to evaluate effectiveness of the treatment? And can ultrashort MRIs be employed to monitor patients?
My expectation is that uptake will be gradual, similar to what we see in other countries around the world. This gives healthcare systems time to adapt as we go. I am confident that EU countries are ready for this. Given the novelty of the treatment, controlled access as recommended by EMA is a good thing.
My recommendation to regulators, however, would be to organize this in such a way that post-authorization study (PAS) and controlled access programme (CAP, see Nov 2024 CHMP opinion) are not in the hands of the pharmaceutical company, but rather in hands of the field. In particular, these studies and protocols should be organized in such a way that they can accommodate future medications as well. For example, the InRAD initiative aims for a registry that can accommodate real-world data collection and post-authorization studies, allowing future comparisons of different treatments. This will be of the utmost importance for the field.
UK Dementia Research Institute@UCL and VIB@KuLeuven
The approval process of lecanemab in Europe has been long, convoluted, and at times baffling. It remains unclear to what extent the final outcome was guided by scientific evidence, and how much was shaped by political dynamics, entrenched skepticism about the amyloid hypothesis, and a pervasive fatalism around Alzheimer’s disease in Europe
The journey began over a year ago with the formal submission of lecanemab’s data package to the European Medicines Agency (EMA). This resulted in an initial rejection on July 25, 2024. An appeal followed, culminating in a revised recommendation for conditional approval—excluding homozygous APOE4 carriers—on November 14, 2024. The file then moved to the European Commission, which referred it to the member states’ standing committee on January 24, 2025. That committee requested confirmation of EMA’s position, which was reaffirmed on February 28.
Still, due to the opaque and overly complex voting mechanism, no qualified majority was reached. This "nondecision" was sent back to the commission, triggering another review by an appeal committee. Only on April 7, 2025—after multiple bureaucratic loops—did the European Commission finally authorize lecanemab for the treatment of early stage Alzheimer’s disease.
Astonishingly, at no point during this process were respected European Alzheimer’s experts consulted. That omission is deeply concerning. Lecanemab is the first approved therapy shown to modify the course of the disease—this should have been a clear and timely decision.
The next challenge is national reimbursement. Each EU member state will now determine whether and to what extent the drug will be covered. Wealthier patients may be able to access treatment regardless, which—while preferable to trans-Atlantic travel for therapy—still creates inequality. For those without the means, access will depend entirely on national health systems. That, too, will be a battle.
Let’s be clear: lecanemab is not a miracle drug. It carries risks—such as ARIA, including brain swelling and microbleeds—especially in APOE4 carriers. But side effects are not uncommon for innovative therapies, including those for cancer or HIV. Importantly, most side effects are only visible on MRI, are largely manageable, and symptomatic cases are relatively rare: Fewer than 6 percent of patients experience headaches or dizziness, and serious complications occur in under 1 percent.
By dragging its feet, the EMA has effectively told Europe’s Alzheimer’s patients that they are second-tier. While the rest of the world cautiously but optimistically adopts disease-modifying treatments, Europe again lags behind. This conservative stance not only delays patient access to innovation—it sends a discouraging signal to researchers and developers. It is particularly ironic, and frankly disheartening, that lecanemab was invented and incubated in Europe by Lars Lannfelt. Where are the European leaders defending and championing innovation born on our own continent?
Even more worrying is that the same Procession of Echternach—three steps forward, two steps back—has already begun for a second drug, donanemab. The EMA has just rejected it, again for reasons that remain unclear and again without consulting any of Europe’s leading Alzheimer’s specialists.
This entire process should serve as a sobering reminder: If Europe wants to lead in science, it must also be willing to act on science.
Hospital de Sant Pau
The authorization for lecanemab by the European Commission represents a big advance for patients and families living with AD in Europe and opens a new era in this disease in Europe. However, the long process taken, the back-and-forth between the CHMP and the commission, and the refusal for marketing authorization for donanemab have raised several concerns among neurologists, other healthcare professionals, and family associations. The general opinion is that there is little knowledge and awareness about AD, even among healthcare professionals who see the disease from a social rather than a medical perspective.
My personal assessment is that AD is still considered by many as an irreversible advanced dementia, linked to aging, with no therapeutic options, without knowledge about the great medical advances in early diagnosis and clinical trials of the last two decades. The way lecanemab has been authorized by the European Commission suggests that much work needs to be done to place AD as a health priority in Europe and to overcome the framework and beliefs used in the last 30 years. This is similar to the situation in cancer 50 years ago. The concern is that this scheme will be also applied to the new drugs that will come in the following years, which may delay further approvals in Europe, mirroring the situation of donanemab.
In Europe, lecanemab is indicated for the treatment of adult patients with a clinical diagnosis of mild cognitive impairment and mild dementia due to AD (early AD) who are ApoE ε4 non-carriers or heterozygotes with confirmed amyloid pathology. This is a restricted indication compared to other countries and will generate the need to obtain more data in the ApoE ε4 homozygote population, who may have a distinct form of disease (Fortea et al., 2024). I hope that the new data and modified drug dosing will facilitate the use of anti-amyloid drugs in AD patients' ApoE ε4 homozygotes. It will be difficult to explain to our patients the lack of access to lecanemab in Europe, especially these first years when it is the only disease-modifying option available.
Despite the controversy, it is clear that the authorization of lecabemab in Europe opens a new era in AD. The large number of patients who are potentially candidates for lecanemab will pose a significant stress on the public health systems across Europe. Besides the cost of the drug, there are several bottlenecks to the implementation of lecanemab in clinical practice, such as shortage of trained specialists, MRI centers, and full hospital daycare centers.
Spain is well-positioned because fluid biomarkers (CSF and plasma) are widely implemented in neurology departments across the public health systems, and Spanish centers are among the top participants in AD clinical trials in Europe. Clinical trials offer an excellent way to train health professionals in the use of these novel therapies. In many centers, clinical trials are performed using separate facilities from clinical routine, with independent personnel and MRI centers. The hospital and the health system will have to adapt the clinical facilities, include MRI centers, and to incorporate new personnel to treat patients with lecanemab and other therapies. This will be an excellent starting point to start this exciting era, which is still in its infancy compared to other therapeutic areas in neurology.
I am the site PI of the Clarity Phase 3 trial and have consulted for Eisai and Lilly.
University of Eastern Finland and Kuopio University Hospital
The EMA’s and European Commission’s approval of lecanemab marks a major milestone for Alzheimer's disease treatment in Europe. It will hopefully serve as a powerful incentive for a rapid transition toward biologically based precision diagnostics across the continent. Furthermore, I hope it encourages both public and private stakeholders to make investments not only in drug development but also in diagnostics and deeper understanding of disease mechanisms.
The extent of lecanemab use is likely to vary between countries. This is largely influenced by existing national diagnostic guidelines and, more importantly, by country-specific reimbursement policies regarding Alzheimer's treatments. For instance, in Finland, while the necessary infrastructure for infusions and monitoring exists, reallocating and prioritizing these resources specifically for memory disorders is needed.
Regarding the EMA’s restrictions, it's a bit early to offer a definitive opinion. I expect that real-world data gathered globally in the coming years will play a crucial role in determining whether the current limitations are well-calibrated or overly conservative.
Perhaps most crucially, this approval represents a shift in how society views neurodegenerative disorders. With disease-modifying treatments entering the scene, we must stop accepting dementia as an “inevitable part of aging.” Instead, we should recognize these conditions as true biological diseases, like cardiovascular disease or cancer, that deserve accurate diagnosis and active treatment to improve quality of life of the patients and their caregivers.
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