Eisai Initiates Rolling Biologics License Application to US FDA for LEQEMBI® (lecanemabirmb) for Subcutaneous Maintenance Dosing for the Treatment of Early Alzheimer’s Disease
Under the Fast Track Status
TOKYO and CAMBRIDGE, Mass., May 15, 2024 – 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 Eisai has initiated the rolling
submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA)
for lecanemab-irmb (U.S. brand name: LEQEMBI®) subcutaneous autoinjector for weekly maintenancedosing after it was granted Fast Track designation by the FDA. LEQEMBI is indicated for the treatmentof Alzheimer’s disease (AD) in patients with Mild Cognitive Impairment (MCI) or mild dementia stage of
disease (collectively referred to as early AD).
The BLA is based on data from the Clarity AD (Study 301) open-label extension (OLE) and modelingof observed data. If approved by the FDA, the LEQEMBI autoinjector could be used to administer
LEQEMBI at home or at medical facilities. The injection process requires less time than the IV
formulation. As part of the subcutaneous autoinjector 360 mg weekly maintenance regimen underreview, patients who have completed the biweekly IV initiation phase would receive weekly doses thatmaintain effective drug concentrations to sustain the clearance of highly toxic protofibrils* which cancontinue to cause neuronal injury even after the amyloid-beta (Aβ) plaque has been cleared from thebrain.
AD is an ongoing neurotoxic process that begins before and continues after plaque deposition. Datasuggest that early and continuing treatment may prolong the benefit even after plaque is cleared fromthe brain. This SC autoinjector is easier for patients and their care partners to use, and may reduce theneed for hospital visits and nursing care compared to intravenous (IV) administration. In addition topotentially maintaining the clinical and biomarker benefits, subcutaneous maintenance dosing may be
more convenient for patients and their care partners to continue the treatment.
LEQEMBI is now approved in the U.S., Japan and China, and applications have been submitted forreview in the European Union, Australia, Brazil, Canada, Hong Kong, Great Britain, India, Israel, Russia,
Saudi Arabia, South Korea, Taiwan, Singapore and Switzerland. Eisai submitted to the FDA a
Supplemental Biologics License Application (sBLA) for monthly LEQEMBI intravenous (IV)maintenance dosing in March 2024.
Eisai serves as the lead for lecanemab’s development and regulatory submissions globally with bothcompanies co-commercializing and co-promoting the product and Eisai having final decision-making
authority.
* Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to be
the most toxic form of Aβ, having a primary role in the cognitive decline associated with this progressive,
debilitating condition.1 Protofibrils cause injury to neurons in the brain, which in turn, can negatively
impact cognitive function via multiple mechanisms, not only increasing the development of insoluble Aβplaques but also increasing direct damage to brain cell membranes and the connections that transmit
signals between nerve cells or nerve cells and other cells. It is believed the reduction of protofibrils may
prevent the progression of AD by reducing damage to neurons in the brain and cognitive dysfunction. 2
INDICATIONLEQEMBI® [(lecanemab-irmb) 100 mg/mL injection for intravenous use] is indicated for the treatment

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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 INFORMATIONWARNING: AMYLOID-RELATED IMAGING ABNORMALITIES (ARIA)
Monoclonal antibodies directed against aggregated forms of amyloid beta,
including LEQEMBI, can cause ARIA, characterized as ARIA withedema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H).
Incidence and timing of ARIA vary among treatments. ARIA usuallyoccurs early in treatment and is asymptomatic, although serious and lifethreatening events, including seizure and status epilepticus, rarely canoccur. Serious intracerebral hemorrhages >1 cm, some fatal, have been
observed with this class of medications.
o Apolipoprotein E ε4 (ApoE ε4) Homozygotes: Patients who are
ApoE ε4 homozygotes (~15% of patients with AD) treated withthis class of medications have a higher incidence of ARIA,
including symptomatic, serious, and severe radiographic ARIA,
compared to heterozygotes and noncarriers. Testing for ApoE
ε4 status should be performed prior to initiation of treatment to
inform the risk of developing ARIA. Prescribers should discusswith patients the risk of ARIA across genotypes and theimplications of genetic testing results. Prescribers should informpatients that if genotype testing is not performed, they can stillbe treated with LEQEMBI; however, it cannot be determined ifthey are ApoE ε4 homozygotes and at higher risk for ARIA.
• Consider the benefit of LEQEMBI for the treatment of AD and thepotential risk of serious ARIA events when deciding to initiate treatment
with LEQEMBI.
•CONTRAINDICATIONLEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any ofthe excipients of LEQEMBI. Reactions have included angioedema and anaphylaxis.
WARNINGS AND PRECAUTIONSAMYLOID-RELATED IMAGING ABNORMALITIESLEQEMBI can cause ARIA-E and ARIA-H, which can occur together. ARIA-E can be observed onmagnetic resonance imaging (MRI) as brain edema or sulcal effusions and ARIA-H as
microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with AD. With
this class of medications, ARIA-H generally occurs in association 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% (29/898) and serious ARIA symptoms in 0.7% (6/898) with
LEQEMBI. Clinical ARIA symptoms resolved in 79% (23/29) of patients during the period of
observation. ARIA, including asymptomatic radiographic events, was observed: LEQEMBI, 21%(191/898); placebo, 9% (84/897). ARIA-E was observed: LEQEMBI, 13% (113/898); placebo, 2%(15/897). ARIA-H was observed: LEQEMBI, 17% (152/898); placebo, 9% (80/897). No increase inisolated ARIA-H was observed for LEQEMBI vs placebo.
ApoE ε4 Carrier Status and Risk of ARIA2

Of the patients taking LEQEMBI, 16% (141/898) were ApoE ε4 homozygotes, 53% (479/898) were
heterozygotes, and 31% (278/898) were noncarriers. With LEQEMBI, the incidence of ARIA washigher 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 eventsoccurred 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
The majority of ARIA-E radiographic events occurred within the first 7 doses, although ARIA canoccur at any time, and patients can have >1 episode. Maximum radiographic severity of ARIA-E
with LEQEMBI was mild in 4% (37/898), moderate in 7% (66/898), and severe in 1% (9/898) of
patients. Resolution of ARIA-E on MRI occurred in 52% of 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% (79/898), moderate in 2% (19/898), and severe in 3% (28/898) of patients;
superficial siderosis was mild in 4% (38/898), moderate in 1% (8/898), and severe in 0.4% (4/898)
of patients. With LEQEMBI, the rate of severe radiographic ARIA-E was highest in ApoE ε4homozygotes (5%; 7/141) vs heterozygotes (0.4%; 2/479) or noncarriers (0%; 0/278). With
LEQEMBI, the rate of severe radiographic ARIA-H was highest in ApoE ε4 homozygotes (13.5%;
19/141) vs heterozygotes (2.1%; 10/479) or noncarriers (1.1%; 3/278).
Intracerebral Hemorrhage
Intracerebral hemorrhage >1 cm in diameter was reported in 0.7% (6/898) with LEQEMBI vs 0.1%
(1/897) with placebo. Fatal events of intracerebral hemorrhage in patients taking LEQEMBI havebeen reported.
Concomitant Antithrombotic Medication:
In Clarity AD, baseline use of antithrombotic medication (aspirin, other antiplatelets, or
anticoagulants) was allowed if the patient was on a stable dose. The majority of exposures toantithrombotic medications were to aspirin. Antithrombotic medications did not increase the riskof ARIA with LEQEMBI. The incidence of intracerebral hemorrhage was 0.9% (3/328) in patientstaking LEQEMBI with a concomitant antithrombotic medication at the time of the event vs 0.6%
(3/545) in those who did not receive an antithrombotic. Patients taking LEQEMBI with an
anticoagulant alone or combined with an antiplatelet medication or aspirin had an incidence of
intracerebral hemorrhage of 2.5% (2/79) vs none in patients receiving placebo. Caution should
be exercised when considering the administration of anticoagulants or a thrombolytic agent (e.g.,
tissue plasminogen activator) to a patient already being treated with LEQEMBI.
Other Risk Factors for Intracerebral Hemorrhage:
Patients were excluded from enrollment in Clarity AD for findings on neuroimaging that indicatedan increased risk for intracerebral hemorrhage. These included findings suggestive of cerebral
amyloid angiopathy (prior cerebral hemorrhage >1 cm in greatest diameter, >4
microhemorrhages,
superficial siderosis, vasogenic edema) or other lesions (aneurysm, vascular malformation). The
presence of an ApoE ε4 allele is also associated with cerebral amyloid angiopathy. Caution
should be exercised when considering the use of LEQEMBI in patients with factors that indicate
an increased risk for intracerebral hemorrhage and in patients who need to be on anticoagulant
therapy.
ARIA Monitoring and Dose Management Guidelines
Obtain a recent baseline brain MRI prior to initiating treatment with LEQEMBI and prior to the 5th, 7th,and 14th infusions. Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks oftreatment with LEQEMBI. 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

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should be performed prior to continuing treatment.
HYPERSENSITIVITY REACTIONSHypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurredwith 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% (237/898); placebo: 7% (66/897)—and the majority of caseswith LEQEMBI (75%, 178/237) occurred with the first infusion. IRRs were mostly mild (69%) or
moderate (28%) in severity. IRRs resulted in discontinuation of LEQEMBI in 1% (12/898). Symptomsof IRRs included fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain),nausea, vomiting, hypotension, hypertension, and oxygen desaturation.
In the event of an IRR, the infusion rate may be reduced or the infusion may be discontinued andappropriate 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 reaction leading to discontinuation of LEQEMBI was ARIA-H
microhemorrhages that led to discontinuation in 2% (15/898) with LEQEMBI vs <1% (1/897) withplacebo.
The most common adverse reactions reported in ≥5% with LEQEMBI (N=898) and ≥2% higher thanplacebo (N=897) 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%).
Please see full Prescribing Information for LEQEMBI, including Boxed WARNING.
MEDIA CONTACTS
Eisai Co., Ltd.
Public Relations Department
TEL: +81 (0)3-3817-5120

Biogen Inc.
Jack Cox+ 1-781-464-3260
public.affairs@biogen.com

Eisai Inc. (U.S.)
Julie Edelman
1-862-213-5915
Julie_Edelman@eisai.com
Eisai Europe, Ltd.
EMEA Communications Department+44 (0) 786 601 1272
Emea-comms@eisai.net

INVESTOR CONTACTS
Eisai Co., Ltd.
Investor Relations Department
TEL: +81 (0) 3-3817-5122

Biogen Inc.
Chuck Triano+ 1-781-464-2442
IR@biogen.com

Notes to Editors41. About lecanemab (LEQEMBI®)
Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. It is ahumanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregatedsoluble (protofibril) and insoluble forms of amyloid-beta (Aβ).3 Lecanemab is approved in the U.S.,4
Japan,5 and China.6. In the U.S., Japan and China, the indications are as follows;• U.S.: For the treatment of Alzheimer’s disease (AD). It should be initiated in patients with
MCI or mild dementia stage of disease.3,7• Japan: For slowing progression of MCI and mild dementia due to AD.5
• China: For the treatment of MCI due to AD and mild AD dementia.6
LEQEMBI’s FDA approval was based on Phase 3 data from Eisai’s, global Clarity AD clinical trial,in which it met its primary endpoint and all key secondary endpoints with statistically significant
results.3 The primary endpoint was the global cognitive and functional scale, Clinical Dementia
Rating Sum of Boxes (CDR-SB). In the Clarity AD clinical trial, treatment with lecanemab reduced
clinical decline on CDR-SB by 27% at 18 months compared to placebo.3 The mean CDR-SB scoreat baseline was approximately 3.2 in both groups. The adjusted least-squares mean change frombaseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, −0.45; 95%
confidence interval [CI], −0.67 to −0.23; P<0.001).3 In addition, the secondary endpoint from theAD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCIADL), which measures information provided by people caring for patients with AD, noted astatistically significant benefit of 37% compared to placebo. 3 The adjusted mean change frombaseline at 18 months in the ADCS-MCI-ADL score was −3.5 in the lecanemab group and −5.5 in
the placebo group (difference, 2.0; 95% CI, 1.2 to 2.8; P<0.001).3 The ADCS MCI-ADL assesses
the ability of patients to function independently, including being able to dress, feed themselves andparticipate in community activities. The most common adverse events (>10%) in the lecanemab
group were infusion reactions, ARIA-H (combined cerebral microhemorrhages, cerebral
macrohemorrhages, and superficial siderosis), ARIA-E (edema/effusion), headache, and fall.3
Eisai has also submitted applications for approval of lecanemab in 14 countries and regions,
including the European Union (EU).
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 theirbrains, 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 andincludes 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 andEisai 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 andcommercialization 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.

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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 humanhealth 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), byworking 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.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 todeliver new medicines to transform patients’ lives and to create value for shareholders and ourcommunities. We apply deep understanding of human biology and leverage different modalities toadvance first-in-class treatments or therapies that deliver superior outcomes. Our approach is totake 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, about the potential clinical effects oflecanemab; 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; andrisks and uncertainties associated with drug development and commercialization. Thesestatements may be identified by words such as "aim," "anticipate," "believe," "could," "estimate,""expect," "forecast," "intend," "may," "plan," "possible," "potential," "will," "would" and other words
and terms of similar meaning. Drug development and commercialization involve a high degree ofrisk, and only a small number of research and development programs result in commercializationof a product. Results in early-stage clinical studies may not be indicative of full results or resultsfrom later stage or larger scale clinical studies and do not ensure regulatory approval. You should
not place undue reliance on these statements.
These statements involve risks and uncertainties that could cause actual results to differ materiallyfrom those reflected in such statements, including without limitation unexpected concerns that may
arise from additional data, analysis or results obtained during clinical studies; the occurrence ofadverse safety events; risks of unexpected costs or delays; the risk of other unexpected hurdles;
regulatory submissions may take longer or be more difficult to complete than expected; regulatory
authorities may require additional information or further studies, or may fail or refuse to approve or
may delay approval of Biogen's drug candidates, including lecanemab; actual timing and content ofsubmissions to and decisions made by the regulatory authorities regarding lecanemab; uncertainty
of success in the development and potential commercialization of lecanemab; failure to protect andenforce Biogen's data, intellectual property and other proprietary rights and uncertainties relating tointellectual property claims and challenges; product liability claims; and third party collaboration
risks, results of operations and financial condition. The foregoing sets forth many, but not all, of the6

factors that could cause actual results to differ from Biogen's expectations in any forward-looking
statement. Investors should consider this cautionary statement as well as the risk factors identified
in Biogen's most recent annual or quarterly report and in other reports Biogen has filed with the U.S.
Securities and Exchange Commission. These statements speak only as of the date of this news
release. Biogen does not undertake any obligation to publicly update any forward-looking
statements.
References
1. 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/s41467-021-23507z
2. 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.
3. LEQEMBI. Prescribing information. Eisai Inc. 2023.
4. US Food and Drug Administration. FDA Grants Accelerated Approval for Alzheimer’s Disease
Treatment. Available at: https://www.fda.gov/news-events/press-announcements/fda-grantsaccelerated-approval-alzheimers-disease-treatment. Last accessed: March 2024.
5. Eisai Global. 2023. “LEQEMBI® Intravenous Infusion” (Lecanemab) Approved for theTreatment of Alzheimer’s Disease in Japan Available at:https://www.eisai.com/news/2023/news202359.html. Last accessed: March 2024.
6. Eisai Global. 2024. “LEQEMBI®” (Lecanemab) Approved for the Treatment of Alzheimer’s
Disease in China. Available at: https://www.eisai.com/news/2024/news202403.html. Last
accessed: March 2024.
7. van Dyck, H., et al. Lecanemab in Early Alzheimer’s Disease. New England Journal of Medicine.
2023;388:9-21. https://www.nejm.org/doi/full/10.1056/NEJMoa2212948.

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