No.23-19March 14, 2023
Eisai Co., Ltd.

U.S. VETERANS’ HEALTH ADMINISTRATION (VHA) PROVIDES COVERAGE OFLEQEMBI™ (LECANEMAB-IRMB) TWO MONTHS AFTER LEQEMBI’S FDAACCELERATED APPROVAL FOR VETERANS LIVING WITH EARLY STAGES OFALZHEIMER’S DISEASEEISAI IS PROUD TO SUPPORT U.S. VETERANS LIVING WITH EARLY STAGES OFALZHEIMER’S DISEASE AND WILL CONTINUE TO TRANSPARENTLY SHARE OUR HIGHQUALITY DATA WITH THE VHA
Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") announced today that the U.S. Veterans’
Health Administration (VHA) is providing coverage of LEQEMBI™ (lecanemab-irmb) to veterans livingwith early stages of Alzheimer’s disease (AD). VHA healthcare professionals meeting the criteria set forth
by the VHA can prescribe LEQEMBI to veterans who fit the VHA’s criteria and the U.S. Food and Drug
Administration’s (FDA) current label. The VHA’s careful consideration and timely action to make
LEQEMBI available approximately two months after the FDA approved LEQEMBI under the accelerated
approval pathway shows its continued commitment to veterans living with AD.
If approved under the traditional pathway, the FDA will update the label for LEQEMBI, which will include
new data that has been evaluated by the FDA. Eisai looks forward to sharing additional high-quality data
as it becomes available and to continuing discussions with the VHA as the company prepares for theFDA’s potential conversion of LEQEMBI’s accelerated approval to a traditional approval. Eisai is proud ofand humbled by the opportunity to support U.S. veterans as we strive to fulfill our human health care(hhc) mission.
LEQEMBI is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against
aggregated soluble (protofibrils*) and insoluble forms of amyloid beta (Aβ), LEQEMBI was approved inthe U.S. under the Accelerated approval Pathway for the treatment of AD on January 6, 2023, and waslaunched in the U.S on January 18, 2023. Treatment with LEQEMBI should only be initiated in patientswith mild cognitive impairment or mild dementia stage of disease and confirmed presence of Aβ pathology.
The Accelerated approval was based on Phase 2 data that demonstrated that LEQEMBI reduced theaccumulation of Aβ plaque in the brain, a defining feature of AD, and its continued approval may becontingent upon verification of LEQEMBI’s clinical benefit in a confirmatory trial. The FDA has determinedthat the results of Clarity AD will serve as the confirmatory study to verify the clinical benefit of LEQEMBI.
On the same day that LEQEMBI received its Accelerated approval, Eisai submitted the supplemental
Biologics License Application (sBLA) to the FDA for approval under the Traditional pathway. The sBLA
was accepted by the FDA on March 3, 2023 and granted Priority Review with a Prescription Drug User
Fee Act (PDUFA) date of July 6, 2023. The sBLA is based on the findings from Eisai’s recently publishedlarge, global confirmatory Phase 3 clinical trial, Clarity AD. LEQEMBI met the primary endpoint and allkey secondary endpoints with highly statistically significant results. In November 2022, results of theClarity AD study were presented at the Clinical Trials on Alzheimer's Disease (CTAD) conference andsimultaneously published in the peer-reviewed medical journal, The New England Journal of Medicine.
Eisai serves as the lead of LEQEMBI development and regulatory submissions globally with both Eisaiand Biogen co-commercializing and co-promoting the product and Eisai having final decision-makingauthority.
* Protofibrils are large Aβ aggregated soluble species of 75-500 Kd.1
To learn more, visit http://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 withLEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit ina confirmatory 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 withLEQEMBI. 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 wereApoE ε4 homozygotes, 2 of whom experienced severe symptoms. An increased incidence of symptomaticand overall ARIA in ApoE ε4 homozygotes compared to heterozygotes and noncarriers in LEQEMBItreated 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 occurred in 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 patientsand severe in 1% (2/161) of patients; 1 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 otherantiplatelet drugs or anticoagulants, limiting any meaningful conclusions about the risk of ARIA or
intracerebral hemorrhage in patients taking other antiplatelet drugs or anticoagulants. Becauseintracerebral hemorrhages >1 cm in diameter have been observed in patients taking LEQEMBI, 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.
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, andsevere small vessel or white matter disease. Caution should be exercised when considering the use ofLEQEMBI in patients with these risk factors.
Infusion-Related Reactions
Infusion-related reactions were observed in LEQEMBI: 20% (32/161); placebo: 3% (8/245); and themajority 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 REACTIONSIn 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 to discontinuationof LEQEMBI was infusion-related reactions that led to discontinuation in 2% (4/161) of patients treatedwith 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 in the U. S.
Media Inquiries:
Public Relations Department,Eisai Co., Ltd.
+81-(0)3-3817-5120

Eisai Inc (U.S.)
Libby Holman
201-753-1945
Libby_Holman@eisai.com
Eisai Europe, Ltd.
(UK, Europe, Australia, New Zealand and Russia)
EMEA Communications Department+44-(0)-786-601-1272
EMEA-comms@eisai.net[Notes to editors]
About LEQEMBITM (lecanemab-irmb)
LEQEMBITM (lecanemab-irmb) is the result of a strategic research alliance between Eisai and BioArctic. LEQEMBI isa humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril)and insoluble forms of amyloid-beta (Aβ). In the U.S., LEQEMBI was granted accelerated approval by the U.S. Foodand Drug Administration (FDA) on January 6, 2023. LEQEMBI is indicated for the treatment of Alzheimer’s disease(AD) in the U.S. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild
dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety oreffectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication isapproved 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.
In the U.S., Eisai submitted a supplemental Biologics License Application (sBLA) to the FDA for approval under thetraditional pathway on January 6, 2023. On March 3, 2023, the FDA accepted Eisai’s sBLA based on the Clarity AD
clinical data, and the LEQEMBI application has been granted Priority Review, with a Prescription Drug User Fee Act(PDUFA) action date of July 6, 2023. The Clarity AD study of lecanemab met its primary endpoint and all key
secondary endpoints with highly statistically significant results. Eisai submitted an application for manufacturing andmarketing approval to the Pharmaceuticals and Medical Devices Agency (PMDA) on January 16, 2023, in Japan. ThePriority Review was granted by the Ministry of Health, Labour and Welfare (MHLW) on January 26, 2023. Eisai utilized
the prior assessment consultation system of PMDA, with the aim of shortening the review period for lecanemab. InEurope, Eisai submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) onJanuary 9, 2023, and accepted on January 26, 2023. In China, Eisai initiated submission of data for a BLA to theNational Medical Products Administration (NMPA) of China in December 2022, and the Priority Review was grantedon February 27, 2023.
Eisai has completed lecanemab subcutaneous bioavailability study, and subcutaneous dosing is currently being
evaluated in the Clarity AD OLE.
Since July 2020, Eisai's Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they areclinically 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 (ACTC) that provides theinfrastructure for academic clinical trials in AD and related dementias in the U.S., funded by the National Institute onAging, 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 byWashington University School of Medicine in St. Louis, has been ongoing since January 2022.
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.
About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercializationof AD treatments. Eisai obtained the global rights to study, develop, manufacture and market LEQEMBI for thetreatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercializationagreement on the antibody LEQEMBI back-up was signed in May 2015.

References
1
Söderberg, L., Johannesson, M., Nygren, P. et al. Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles
to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s
Disease. Neurotherapeutics (2022). https://doi.org/10.1007/s13311-022-01308-6. Accessed February 9, 2023##