Eisai Submits Supplemental Biologics License Application to FDA for Traditional Approval of
LEQEMBI™ (lecanemab-irmb) for the Treatment of Alzheimer’s Disease
Submission for traditional approval follows FDA accelerated approval of LEQEMBI on the same day, andis based on data from the confirmatory Phase 3 Clarity AD clinical trial
TOKYO and CAMBRIDGE, Mass., January 6, 2023 – Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo
Naito, “Eisai”) and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO:
Christopher A. Viehbacher “Biogen”) announced Eisai has submitted a supplemental Biologics License
Application (sBLA) to the U.S. Food and Drug Administration (FDA) supporting the conversion of the
Accelerated Approval of LEQEMBI™ (lecanemab-irmb) 100 mg/mL injection for intravenous use to a
traditional approval. This sBLA is subject to validation of whether the FDA accepts the application for review.
LEQEMBI is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against
aggregated soluble (“protofibrils”)* and insoluble forms of amyloid beta (Aβ), approved under Accelerated
Approval Pathway by the FDA on January 6, 2023, for the treatment of Alzheimer’s Disease (AD).
Treatment with LEQEMBI should only be initiated in patients with the mild cognitive impairment or mild
dementia stage of disease and confirmed presence of Aβ pathology.
Accelerated Approval of LEQEMBI was based on Phase 2 data that demonstrated LEQEMBI reduced theaccumulation of Aβ plaque in the brain, a defining feature of AD. Continued approval for this indication iscontingent upon verification of LEQEMBI’s clinical benefit in a confirmatory trial. The sBLA for LEQEMBI isbased on the data from the Phase 3 confirmatory Clarity AD clinical trial. In Clarity AD, LEQEMBI met the
primary endpoint and all key secondary endpoints with highly statistically significant results, and the profile
of Amyloid-Related Imaging Abnormalities (ARIA) incidence was within expectations. In November 2022,
the results of the Clarity AD study were presented at the 2022 Clinical Trials on Alzheimer’s Disease (CTAD)
conference, and simultaneously published in the New England Journal of Medicine, peer-reviewed medical
journals.
“We deeply appreciate the cooperation of people living with Alzheimer’s disease and healthcare
professionals who participated in LEQEMBI’s Phase 3 Clarity AD clinical study, which enabled us to submit
this sBLA. Alzheimer’s disease causes significant impairment and burden to both the people living with thisdisease and their families, as well as having a profound impact on society,” said Haruo Naito, Chief
Executive Officer at Eisai. “The fact that Eisai was able to file LEQEMBI’s supplemental Biologics License
Application for traditional FDA approval on the same day we received accelerated approval demonstrates
our commitment to the Alzheimer’s disease community and is a major step forward in ensuring access for
all those in the U.S living with this disease in need of this medicine. We will continue to actively cooperatewith the FDA's review.”
Eisai has initiated submission of data for BLA to the National Medical Products Administration (NMPA) of
China in December 2022. Eisai plans to file for marketing authorization applications of lecanemab in Japanand EU by the end of Eisai’s FY2022, which ends March 31, 2023.
“Today’s filing is an important milestone for people living with Alzheimer’s disease, demonstrating theresilience of the scientific and medical communities in their fight against this terrible disease despite themany setbacks and the challenges they’ve faced,” said Christopher A. Viehbacher, President and Chief
Executive Officer of Biogen. “We commend Eisai for their leadership on the development of lecanemab andfor the speed in which they were able to complete this filing, which is based on important new data from thepivotal late-stage Clarity AD study.”
Eisai serves as the lead of LEQEMBI development and regulatory submissions globally with both Eisai and
Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority.
* Protofibrils are large Aβ aggregated soluble species of 75-500 Kd. 1, 2
To learn more, visit www.LEQEMBI.com.

INDICATION, DOSAGE AND ADMINISTRATION, AND IMPORTANT SAFETY INFORMATION IN THE
U.S
INDICATIONLEQEMBI is indicated for the treatment of Alzheimer’s disease. Treatment with LEQEMBI should beinitiated in patients with mild cognitive impairment or mild dementia stage of disease, the population inwhich treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating
treatment at earlier or later stages of the disease than were studied. This indication is approved under
accelerated approval based on reduction in amyloid beta plaques observed in patients treated with
LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in aconfirmatory trial.
IMPORTANT SAFETY INFORMATIONWARNINGS AND PRECAUTIONS
Amyloid Related Imaging Abnormalities• LEQEMBI can cause amyloid related imaging abnormalities-edema (ARIA-E) and -hemosiderin
deposition (ARIA-H). ARIA-E can be observed on MRI as brain edema or sulcal effusions, and ARIA-H
as microhemorrhage and superficial siderosis. ARIA is usually asymptomatic, although serious and lifethreatening events, including seizure and status epilepticus, rarely can occur. Reported symptoms
associated with ARIA may include headache, confusion, visual changes, dizziness, nausea, and gaitdifficulty. Focal neurologic deficits may also occur. Symptoms associated with ARIA usually resolve overtime.
ARIA Monitoring and Dose Management Guidelines• Obtain recent (within one year) brain magnetic resonance imaging (MRI) prior to initiating treatment with
LEQEMBI. Obtain an MRI prior to the 5th, 7th, and 14th infusions.
• Recommendations for dosing in patients with ARIA-E and ARIA-H depend on clinical symptoms andradiographic severity. Depending on ARIA severity, use clinical judgment in considering whether tocontinue dosing, temporarily discontinue treatment, or permanently discontinue LEQEMBI.
• Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with
LEQEMBI. If a patient experiences symptoms suggestive of ARIA, 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.
• There is no experience in patients who continued dosing through symptomatic ARIA-E or throughasymptomatic, but radiographically severe, ARIA-E. There is limited experience in patients who
continued dosing through asymptomatic but radiographically mild to moderate ARIA-E. There are limited
data in dosing patients who experienced recurrent ARIA-E.
Incidence of ARIA
• In Study 1 (Study 201), symptomatic ARIA occurred in 3% (5/161) of LEQEMBI-treated patients. Clinicalsymptoms associated with ARIA resolved in 80% of patients during the period of observation.
• Including asymptomatic cases, ARIA was observed in LEQEMBI: 12% (20/161); placebo: 5% (13/245).
ARIA-E was observed in LEQEMBI: 10% (16/161); placebo: 1% (2/245). ARIA-H was observed in
LEQEMBI: 6% (10/161); placebo: 5% (12/245). There was no increase in isolated ARIA-H for LEQEMBI
compared to placebo.
• Intracerebral hemorrhage >1 cm in diameter was reported after one treatment in LEQEMBI: 1 patient;placebo: zero patients. Events of intracerebral hemorrhage, including fatal events, in patients taking
LEQEMBI have also been reported in other studies.

Apolipoprotein E ε4 (ApoE ε4) Carrier Status and Risk of ARIA
• In Study 1, 6% (10/161) of patients in the LEQEMBI group were ApoE ε4 homozygotes, 24% (39/161)
were heterozygotes, and 70% (112/161) were noncarriers.
• The incidence of ARIA was higher in ApoE ε4 homozygotes than in heterozygotes and noncarriers
among patients treated with LEQEMBI. Of the 5 LEQEMBI-treated patients who had symptomatic ARIA,
4 were ApoE ε4 homozygotes, 2 of whom experienced severe symptoms. An increased incidence ofsymptomatic and overall ARIA in ApoE ε4 homozygotes compared to heterozygotes and noncarriers in
LEQEMBI-treated patients has been reported in other studies.
• The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers.
• Consider testing for ApoE ε4 status to inform the risk of developing ARIA when deciding to initiate
treatment with LEQEMBI.
Radiographic Findings• The majority of ARIA-E radiographic events occurred early in treatment (within the first 7 doses),although ARIA can occur at any time and patients can have more than 1 episode. The maximum
radiographic severity of ARIA-E in patients treated with LEQEMBI was mild in 4% (7/161) of patients,
moderate in 4% (7/161) of patients, and severe in 1% (2/161) of patients. Resolution on MRI occurredin 62% of ARIA-E patients by 12 weeks, 81% by 21 weeks, and 94% overall after detection. The
maximum radiographic severity of ARIA-H microhemorrhage in patients treated with LEQEMBI was mild
in 4% (7/161) of patients and severe in 1% (2/161) of patients; of the 10 patients with ARIA-H had mild
superficial siderosis.
Concomitant Antithrombotic Medication and Other Risk Factors for Intracerebral Hemorrhage• Patients were excluded from enrollment in Study 1 for baseline use of anticoagulant medications.
Antiplatelet medications such as aspirin and clopidogrel were allowed. If anticoagulant medication wasused because of intercurrent medical events that required treatment for ≤4 weeks, treatment with
LEQEMBI was to be temporarily suspended.
• Most exposures to antithrombotic medications were to aspirin; few patients were exposed to otherantiplatelet drugs or anticoagulants, limiting any meaningful conclusions about the risk of ARIA or
intracerebral hemorrhage in patients taking other antiplatelet drugs or anticoagulants. Because
intracerebral hemorrhages >1 cm in diameter have been observed in patients taking LEQEMBI,
additional caution should be exercised when considering the administration of antithrombotics or athrombolytic agent (e.g., tissue plasminogen activator) to a patient already being treated with LEQEMBI.
• Patients were excluded from enrollment in Study 1 for the following risk factors for intracerebral
hemorrhage: prior cerebral hemorrhage >1 cm in greatest diameter, more than 4 microhemorrhages,
superficial siderosis, evidence of vasogenic edema, evidence of cerebral contusion, aneurysm, vascularmalformation, infective lesions, multiple lacunar infarcts or stroke involving a major vascular territory,
and severe small vessel or white matter disease. Caution should be exercised when considering the useof LEQEMBI in patients with these risk factors.
Infusion-Related Reactions• Infusion-related reactions were observed in LEQEMBI: 20% (32/161); placebo: 3% (8/245), and the
majority of cases in LEQEMBI-treated patients (88%, 28/32) occurred with the first infusion. All infusionrelated reactions were mild (56%) or moderate (44%) in severity. Infusion-related reactions resulted indiscontinuations in 2% (4/161) of patients treated with LEQEMBI. Symptoms of infusion-related
reactions included fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain),nausea, vomiting, hypotension, hypertension, and oxygen desaturation.
• After the first infusion, 38% of LEQEMBI-treated patients had transient decreased lymphocyte counts to<0.9 x109/L compared to 2% on placebo, and 22% of LEQEMBI-treated patients had transient increased
neutrophil counts to >7.9 x109/L compared to 1% on placebo.

• In the event of an infusion-related reaction, the infusion rate may be reduced, or the infusion may bediscontinued, and appropriate therapy initiated as clinically indicated. Prophylactic treatment withantihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids prior to future
infusions may be considered.
ADVERSE REACTIONS• In Study 1, 15% of LEQEMBI-treated patients, compared to 6% of placebo-treated patients, stopped
study treatment because of an adverse reaction. The most common adverse reaction leading todiscontinuation of LEQEMBI was infusion-related reactions that led to discontinuation in 2% (4/161) ofpatients treated with LEQEMBI compared to 1% (2/245) of patients on placebo.
• The most common adverse reactions reported in ≥5% of patients treated with LEQEMBI (N=161) and≥2% higher than placebo (N=245) in Study 1 were infusion-related reactions (LEQEMBI: 20%; placebo:3%), headache (LEQEMBI: 14%; placebo: 10%), ARIA-E (LEQEMBI: 10%; placebo: 1%), cough(LEQEMBI: 9%; placebo: 5%), and diarrhea (LEQEMBI: 8%; placebo: 5%).
Please see full Prescribing Information.
Media Contacts:
Eisai Co., Ltd.
Public Relations Department
TEL: +81 (0)3-3817-5120

Biogen Inc.
Natacha Gassenbach+ 1-857-777-6573
public.affairs@biogen.com

Eisai Inc. (U.S.)
Libby Holman+ 1-201-753-1945
Libby_Holman@eisai.com
Eisai Europe, Ltd.
(Europe, Australia, New Zealand and Russia)
EMEA Communications Department
EMEA-comms@eisai.net+44 (0) 786 601 1272
Investor Contacts:
Eisai Co., Ltd.
Investor Relations Department
TEL: +81 (0) 3-3817-5122

Biogen Inc.
Mike Hencke+ 1-781-464-2442
IR@biogen.com

Notes to Editors
1. About LEQEMBITM (lecanemab-irmb)
LEQEMBITM (lecanemab-irmb) is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody thatis directed against aggregated soluble (“protofibrils”) and insoluble forms of amyloid-beta (Aβ). LEQEMBI
is indicated for the treatment of Alzheimer’s disease (AD) in the U.S. Treatment with LEQEMBI should beinitiated in patients with mild cognitive impairment or mild dementia stage of disease, the population inwhich treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating
treatment at earlier or later stages of the disease than were studied. This indication is approved under
accelerated approval based on reduction in Aβ plaques observed in patients treated with LEQEMBI.

Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory
trial.
LEQEMBI is the result of a strategic research alliance between Eisai and BioArctic. Eisai has been initiatedsubmission of data for the BLA to the National Medical Products Administration (NMPA) of China in
December 2022. Eisai plans to file for marketing authorization applications of lecanemab in Japan and EU
by the end of Eisai’s FY2022.
Since July 2020, Eisai’s 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 Consortiumthat provides the infrastructure for academic clinical trials in AD and related dementias in the U.S., fundedby the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen.
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, has been ongoing since January 2022. Eisai has completed a LEQEMBI subcutaneous bioavailability
study, and subcutaneous dosing is currently being evaluated in the Clarity AD (Study 301) OLE.
2. About Amyloid-Related Imaging Abnormalities (ARIA)
ARIA is an important adverse event of amyloid-lowering therapies that is critical to monitor and manage
during treatment. ARIA is most commonly seen as temporary swelling/effusion (ARIA-E) in areas of thebrain that usually resolves over time. Some people may also have small spots of bleeding in or on thesurface of the brain (ARIA-H) with the swelling. Although most people with ARIA-E do not have symptoms,
some people may have symptoms such as headache, confusion, dizziness, vision changes and nausea.
3. 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, withboth companies co-commercializing and co-promoting the product and Eisai having final decision-making
authority.
4. 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 andmarket LEQEMBI for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The
development and commercialization agreement on the antibody LEQEMBI back-up was signed in May
2015.
5. About Eisai Co., Ltd.
Eisai's Corporate Concept is “to give first thought to patients and people in the daily living domain, and toincrease the benefits that health care provides.” Under this concept (also known as the human health care[hhc] concept), we aim to effectively achieve social good in the form of relieving anxiety over health andreducing 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.), andconnect with us on Twitter @Eisai_SDGs.
6. About Biogen
As pioneers in neuroscience, Biogen discovers, develops and delivers worldwide innovative therapies forpeople living with serious neurological diseases as well as related therapeutic adjacencies. One of theworld’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz
Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has
a leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for
spinal muscular atrophy, and developed the first and only approved treatment to address a defining
pathology of Alzheimer’s disease. Biogen is also commercializing biosimilars and focusing on advancing
one of the industry’s most diversified pipelines in neuroscience that will transform the standard of care forpatients in several areas of high unmet need.
The company routinely posts information that may be important to investors on its website atwww.biogen.com. To learn more, please visit www.biogen.com and Follow Biogen on social media – Twitter,
LinkedIn, Facebook, YouTube.
Biogen Safe Harbor
This news release contains forward-looking statements, including statements made pursuant to the safe
harbor provisions of the Private Securities Litigation Reform Act of 1995, about the potential clinical effectsof lecanemab; 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 anticipatedbenefits and potential of Biogen's collaboration arrangements with Eisai; the potential of Biogen'scommercial business and pipeline programs, including lecanemab; and risks and uncertainties associatedwith drug development and commercialization. These statements 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 of risk, and only a small number of research and development programs result incommercialization of a product. Results in early-stage clinical studies may not be indicative of full results or
results from later stage or larger scale clinical studies and do not ensure regulatory approval. You should
not place undue reliance on these statements or the scientific data presented.
These statements involve risks and uncertainties that could cause actual results to differ materially fromthose reflected in such statements, including without limitation unexpected concerns that may arise fromadditional data, analysis or results obtained during clinical studies, including the Clarity AD clinical trial and
AHEAD 3-45 study; the occurrence of adverse safety events; risks of unexpected costs or delays; the riskof 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 andcontent of submissions to and decisions made by the regulatory authorities regarding lecanemab;
uncertainty of success in the development and potential commercialization of lecanemab; failure to protect
and enforce Biogen's data, intellectual property and other proprietary rights and uncertainties relating tointellectual property claims and challenges; product liability claims; third party collaboration risks; and the
direct and indirect impacts of the ongoing COVID-19 pandemic on Biogen's business, results of operations
and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual
results to differ from Biogen's expectations in any forward-looking statement. Investors should consider thiscautionary statement as well as the risk factors identified in Biogen's most recent annual or quarterly reportand in other reports Biogen has filed with the U.S. Securities and Exchange Commission. These statements
are based on Biogen's current beliefs and expectations and speak only as of the date of this news release.
Biogen does not undertake any obligation to publicly update any forward-looking statements, whether as aresult of new information, future developments or otherwise.
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