TOKYO and CAMBRIDGE, Mass., Dec. 2, 2025 /PRNewswire/ -- Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Christopher A. Viehbacher, "Biogen") announced today that the latest data confirming the pharmacological effect of lecanemab (generic name, U.S. brand name: LEQEMBI^®), an anti-Aβ protofibril* antibody, on Aβ protofibrils (PF) in cerebrospinal fluid (CSF) was presented at the 18th Clinical Trials on Alzheimer's Disease (CTAD) Conference. The findings represent the results from a large-scale clinical study demonstrating, for the first time, that binding of lecanemab to PF can be measured in CSF, enabling further understanding of how lecanemab slows Alzheimer's disease (AD) progression.

AD is a progressive, relentless disease with Aβ and tau as hallmarks. It is caused by a continuous underlying neurotoxic process driven by PF that begins before amyloid plaque accumulation and continues after plaque removal.^1,2,3 Only LEQEMBI fights AD in two ways: targeting both protofibrils and amyloid plaque, which can impact tau downstream.

In a CSF sub-cohort (n=410) of the Phase III Clarity AD study, total PF concentration in CSF was quantified using an ultrasensitive assay. Changes from baseline (pre-treatment) for the placebo group (natural course) and the lecanemab group were compared, and associations between PF changes and neurodegeneration biomarkers were analyzed.

Total CSF PF concentration in the placebo group increased by 19% at 12 months and 29% at 18 months. In contrast, the lecanemab group showed a 59% increase at 12 months and a 45% increase at 18 months. At 12 months, the difference compared with placebo was statistically significant (p=0.0126).

The increase in total CSF PF with lecanemab treatment suggests that lecanemab binds to PF (target engagement) and facilitates its mobilization from the vicinity of Aβ plaques within the brain parenchyma into the CSF (pharmacodynamic effect). This suggests that lecanemab is having the desired effect of mitigating the toxic effects of PF by mobilizing it outside of the brain parenchyma.

In the placebo group, a statistically significant correlation was observed between changes in CSF PF and changes in neurodegeneration biomarkers (total tau, neurogranin) as well as tau pathology biomarkers (p-tau181, MTBR-tau243**) at baseline. This correlation disappeared with lecanemab treatment, suggesting that lecanemab reduces neurotoxicity by binding to PF.

These findings reinforce lecanemab as the only AD treatment that targets neurotoxic PF and Aβ plaques, resulting in slower tau tangle accumulation on PET imaging.

Eisai serves as the lead for lecanemab's development and regulatory submissions globally with Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority.

* Protofibrils are thought to be the most toxic Aβ species that contribute to brain damage in AD and play a major role in the cognitive decline of this progressive and devastating disease. Protofibrils can cause neuronal and synaptic damage in the brain, which can subsequently adversely affect cognitive function through multiple mechanisms.³ The mechanism by which this occurs has been reported not only by increasing the formation of insoluble Aβ plaques, but also by directly damaging signaling between neurons and other cells. It is believed that reducing protofibrils may reduce neuronal damage and cognitive impairment, potentially preventing the progression of AD.⁴

** MTBR-tau243 is a novel biomarker composed of tau fragments that include residue 243 and the microtubule binding region, and is thought to arise during the formation of neurofibrillary tangles, a key pathological feature of AD. It has also been shown to have a strong correlation with tau PET.⁵

INDICATION
LEQEMBI^® is indicated for the treatment of Alzheimer's disease (AD). Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATION
Contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients. Reactions have included angioedema and anaphylaxis.

WARNINGS AND PRECAUTIONS

Amyloid-Related Imaging Abnormalities
Medications in this class, including LEQEMBI, can cause ARIA-E, which can be observed on MRI as brain edema or sulcal effusions, and ARIA-H, which includes microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with AD, particularly in patients with MRI findings suggestive of cerebral amyloid angiopathy (CAA), such as pretreatment microhemorrhage or superficial siderosis. ARIA-H generally occurs with ARIA-E. Reported ARIA symptoms may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms usually resolve over time.

Incidence of ARIA
Symptomatic ARIA occurred in 3% and serious ARIA symptoms in 0.7% with LEQEMBI. Clinical ARIA symptoms resolved in 79% of patients during the period of observation. ARIA, including asymptomatic radiographic events, was observed: LEQEMBI, 21%; placebo, 9%. ARIA-E was observed: LEQEMBI, 13%; placebo, 2%. ARIA-H was observed: LEQEMBI, 17%; placebo, 9%. No increase in isolated ARIA-H was observed for LEQEMBI vs placebo.

Incidence of ICH
ICH >1 cm in diameter was reported in 0.7% with LEQEMBI vs 0.1% with placebo. Fatal events of ICH in patients taking LEQEMBI have been observed.

Risk Factors of ARIA and ICH

ApoE ε4 Carrier Status
Of the patients taking LEQEMBI, 16% were ApoE ε4 homozygotes, 53% were heterozygotes, and 31% were noncarriers. With LEQEMBI, ARIA was higher in ApoE ε4 homozygotes (LEQEMBI: 45%; placebo: 22%) than in heterozygotes (LEQEMBI: 19%; placebo: 9%) and noncarriers (LEQEMBI: 13%; placebo: 4%). Symptomatic ARIA-E occurred in 9% of ApoE ε4 homozygotes vs 2% of heterozygotes and 1% of noncarriers. Serious ARIA events occurred in 3% of ApoE ε4 homozygotes and in ~1% of heterozygotes and noncarriers. The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers.

Radiographic Findings of CAA
Neuroimaging findings that may indicate CAA include evidence of prior ICH, cerebral microhemorrhage, and cortical superficial siderosis. CAA has an increased risk for ICH. The presence of an ApoE ε4 allele is also associated with CAA.

The baseline presence of at least 2 microhemorrhages or the presence of at least 1 area of superficial siderosis on MRI, which may be suggestive of CAA, have been identified as risk factors for ARIA. Patients were excluded from Clarity AD for the presence of >4 microhemorrhages and additional findings suggestive of CAA (prior cerebral hemorrhage >1 cm in greatest diameter, superficial siderosis, vasogenic edema) or other lesions (aneurysm, vascular malformation) that could potentially increase the risk of ICH.

Concomitant Antithrombotic or Thrombolytic Medication
In Clarity AD, baseline use of antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) was allowed if the patient was on a stable dose. Most exposures were to aspirin. Antithrombotic medications did not increase the risk of ARIA with LEQEMBI. The incidence of ICH: 0.9% in patients taking LEQEMBI with a concomitant antithrombotic medication vs 0.6% with no antithrombotic and 2.5% in patients taking LEQEMBI with an anticoagulant alone or with antiplatelet medication such as aspirin vs none in patients receiving placebo.

Fatal cerebral hemorrhage has occurred in 1 patient taking an anti-amyloid monoclonal antibody in the setting of focal neurologic symptoms of ARIA and the use of a thrombolytic agent.

Additional caution should be exercised when considering the administration of antithrombotics or a thrombolytic agent (e.g., tissue plasminogen activator) to a patient already being treated with LEQEMBI. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, treating clinicians should consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy in a patient being treated with LEQEMBI.

Caution should be exercised when considering the use of LEQEMBI in patients with factors that indicate an increased risk for ICH and, in particular, patients who need to be on anticoagulant therapy or patients with findings on MRI that are suggestive of CAA.

Radiographic Severity With LEQEMBI
Most ARIA-E radiographic events occurred within the first 7 doses, although ARIA can occur at any time, and patients can have >1 episode. Maximum radiographic severity of ARIA-E with LEQEMBI was mild in 4%, moderate in 7%, and severe in 1% of patients. Resolution on MRI occurred in 52% of ARIA-E patients by 12 weeks, 81% by 17 weeks, and 100% overall after detection. Maximum radiographic severity of ARIA-H microhemorrhage with LEQEMBI was mild in 9%, moderate in 2%, and severe in 3% of patients; superficial siderosis was mild in 4%, moderate in 1%, and severe in 0.4% of patients. With LEQEMBI, the rate of severe radiographic ARIA-E was highest in ApoE ε4 homozygotes (5%) vs heterozygotes (0.4%) or noncarriers (0%). With LEQEMBI, the rate of severe radiographic ARIA-H was highest in ApoE ε4 homozygotes (13.5%) vs heterozygotes (2.1%) or noncarriers (1.1%).

Monitoring and Dose Management Guidelines
Baseline brain MRI and periodic monitoring with MRI are recommended. Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment. Depending on ARIA-E and ARIA-H clinical symptoms and radiographic severity, use clinical judgment when considering whether to continue dosing or to temporarily or permanently discontinue LEQEMBI. If a patient experiences ARIA symptoms, clinical evaluation should be performed, including MRI if indicated. If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment.

Hypersensitivity Reactions
Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred with LEQEMBI. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction and initiate appropriate therapy.

Infusion-Related Reactions (IRRs)
IRRs were observed—LEQEMBI: 26%; placebo: 7%—and most cases with LEQEMBI (75%) occurred with the first infusion. IRRs were mostly mild (69%) or moderate (28%). Symptoms included fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation.

IRRs can occur during or after the completion of infusion. In the event of an IRR during the infusion, the infusion rate may be reduced or discontinued, and appropriate therapy initiated as clinically indicated. Consider prophylactic treatment prior to future infusions with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids.

ADVERSE REACTIONS

• The most common adverse reactions reported in ≥5% with LEQEMBI infusion every 2 weeks and ≥2% higher than placebo were IRRs (LEQEMBI: 26%; placebo: 7%), ARIA-H (LEQEMBI: 14%; placebo: 8%), ARIA-E (LEQEMBI: 13%; placebo: 2%), headache (LEQEMBI: 11%; placebo: 8%), superficial siderosis of central nervous system (LEQEMBI: 6%; placebo: 3%), rash (LEQEMBI: 6%; placebo: 4%), and nausea/vomiting (LEQEMBI: 6%; placebo: 4%)
• Safety profile of LEQEMBI IQLIK for maintenance treatment was similar to LEQEMBI infusion. Patients who received LEQEMBI IQLIK experienced localized and systemic (less frequent) injection-related reactions (mild to moderate in severity)

LEQEMBI (lecanemab-irmb) is available:

• Intravenous infusion: 100 mg/mL
• Subcutaneous injection: 200 mg/mL

Please see full Prescribing Information for LEQEMBI, including Boxed WARNING.

Notes to Editors

1. About lecanemab (generic name, brand name: LEQEMBI^®)
   Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. It is a humanized immunoglobulin gamma (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ).
     
   Lecanemab has been approved in 51 countries and regions including Japan, the United States, Europe, China, South Korea, Taiwan, and Saudi Arabia, and is under regulatory review in 9 countries. LEQEMBI received manufacturing and marketing approval in Japan on September 2023 for the indication of slowing progression of mild cognitive impairment (MCI) and mild dementia due to Alzheimer's disease (AD). Following the initial phase with treatment every two weeks for 18 months, intravenous (IV) maintenance dosing with treatment every four weeks was approved in the U.S., China, the United Kingdom, and others, and applications have been filed in 4 countries and regions. The U.S. FDA approved Eisai's Biologics License Application (BLA) for subcutaneous maintenance dosing with LEQEMBI IQLIK in August 2025. A rolling Supplemental Biologics License Application (sBLA) for initiation treatment was initiated under Fast Track status in September 2025, and completed in November 2025. In November 2025, an application for a subcutaneous injectable formulation in Japan was submitted.
     
   Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer's Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen. Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing and includes lecanemab as the backbone anti-amyloid therapy.
     
2. About the Collaboration between Eisai and Biogen for AD
   Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
     
3. About the Collaboration between Eisai and BioArctic for AD
   Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market lecanemab for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody lecanemab back-up was signed in May 2015.
     
4. About Eisai Co., Ltd.
   Eisai's Corporate Concept is "to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides." Under this Concept (also known as human health care (hhc) Concept), we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.
     
   In addition, we demonstrate our commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), by working on various activities together with global partners.
     
   For more information about Eisai, please visit www.eisai.com (for global headquarters: Eisai Co., Ltd.), and connect with us on X, LinkedIn and Facebook. The website and social media channels are intended for audiences outside of the UK and Europe. For audiences based in the UK and Europe, please visit www.eisai.eu and Eisai EMEA LinkedIn.
     
5. About Biogen
   Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patient's lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth.
     
   The company routinely posts information that may be important to investors on its website at www.biogen.com. Follow Biogen on social media – Facebook, LinkedIn, X, YouTube.

Biogen Safe Harbor
This news release contains forward-looking statements, including about the potential clinical effects of lecanemab (LEQEMBI); the potential benefits, safety and efficacy of lecanemab; potential regulatory discussions, submissions and approvals and the timing thereof; the treatment of Alzheimer's disease; the anticipated benefits and potential of Biogen's collaboration arrangements with Eisai; the potential of Biogen's commercial business and pipeline programs, including lecanemab; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be accompanied by such words as "aim," "anticipate," "believe," "contemplate," "continue," "could," "estimate," "expect," "forecast," "goal," "guidance", "hope," "intend," "may," "objective," "plan," "possible," "potential," "predict," "project," "prospect," "should," "target," "will," "would: and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements. Given their forward-looking nature, these statements involve substantial risks and uncertainties that may be based on inaccurate assumptions and could cause actual results to differ materially from those reflected in such statements.

These forward-looking statements are based on management's current beliefs and assumptions and on information currently available to management. Given their nature, we cannot assure that any outcome expressed in these forward-looking statements will be realized in whole or in part. We caution that these statements are subject to risks and uncertainties, many of which are outside of our control and could cause future events or results to be materially different from those stated or implied in this document, including, among others, uncertainty of our long-term success in developing, licensing, or acquiring other product candidates or additional indications for existing products; expectations, plans, prospects and timing of actions relating to product approvals, approvals of additional indications for our existing products, sales, pricing, growth, reimbursement and launch of our marketed and pipeline products; the potential impact of increased product competition in the biopharmaceutical and healthcare industry, as well as any other markets in which we compete, including increased competition from new originator therapies, generics, prodrugs and biosimilars of existing products and products approved under abbreviated regulatory pathways; our ability to effectively implement our corporate strategy; difficulties in obtaining and maintaining adequate coverage, pricing, and reimbursement for our products; the drivers for growing our business, including our dependence on collaborators and other third parties for the development, regulatory approval, and commercialization of products and other aspects of our business, which are outside of our full control; risks related to commercialization of biosimilars, which is subject to such risks related to our reliance on third-parties, intellectual property, competitive and market challenges and regulatory compliance; the risk that positive results in a clinical trial may not be replicated in subsequent or confirmatory trials or success in early stage clinical trials may not be predictive of results in later stage or large scale clinical trials or trials in other potential indications; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; and the occurrence of adverse safety events, restrictions on use with our products, or product liability claims; and any other risks and uncertainties that are described in other reports we have filed with the U.S. Securities and Exchange Commission, which are available on the SEC's website at www.sec.gov.

These statements speak only as of the date of this press release and are based on information and estimates available to us at this time. Should known or unknown risks or uncertainties materialize or should underlying assumptions prove inaccurate, actual results could vary materially from past results and those anticipated, estimated or projected. Investors are cautioned not to put undue reliance on forward-looking statements. A further list and description of risks, uncertainties and other matters can be found in our Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and in our subsequent reports on Form 10-Q. Except as required by law, we do not undertake any obligation to publicly update any forward-looking statements whether as a result of any new information, future events, changed circumstances or otherwise.

Digital Media Disclosures
From time to time, we have used, or expect in the future to use, our investor relations website (investors.biogen.com), the Biogen LinkedIn account (linkedin.com/company/biogen-) and the Biogen X account (https://x.com/biogen) as a means of disclosing information to the public in a broad, non-exclusionary manner, including for purposes of the SEC's Regulation Fair Disclosure (Reg FD). Accordingly, investors should monitor our investor relations website and these social media channels in addition to our press releases, SEC filings, public conference calls and websites, as the information posted on them could be material to investors.

References

1. Iwatsubo T, Irizarry M, van Dyck C, Sabbagh M, Bateman RJ, Cohen S. Clarity AD: a phase 3 placebo-controlled, double-blind, parallel-group, 18-month study evaluating lecanemab in early Alzheimer's disease. Presented at: CTAD Conference; November 29-December 2, 2022; San Francisco, CA.
2. Hampel H, Hardy J, Blennow K, et al. The amyloid-β pathway in Alzheimer's disease. Mol Psychiatry. 2021;26(10):5481-5503.
3. Amin L, Harris DA. Aβ receptors specifically recognize molecular features displayed by fibril ends and neurotoxic oligomers. Nat Commun. 2021; 12:3451. doi: 10.1038/s41467-021-23507-z.
4. Ono K, Tsuji M. Protofibrils of Amyloid-β are Important Targets of a Disease-Modifying Approach for Alzheimer's Disease. Int J Mol Sci. 2020;21(3):952. doi: 10.3390/ijms21030952. PMID: 32023927; PMCID: PMC7037706.
5. Horie et al., CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer's disease. Nat Med 29, 1954–1963 (2023). https://doi.org/10.1038/s41591-023-02443-z.

 

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