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tokyo and cambridge, mass., january 30, 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 today that an application for manufacturing and marketing approval for lecanemab (generic name, u.s. brand name: leqembi™), an anti-amyloid-β (aβ) protofibril^* antibody, in japan has been designated for priority review by the japanese ministry of health, labour and welfare (mhlw). priority review in japan is granted to new medicines recognized as having high medical utility for serious diseases, and once designated for priority review, the target total review period is shortened.

in japan, eisai submitted the manufacturing and marketing approval for lecanemab to the pharmaceuticals and medical devices agency (pmda) on january 16, 2023. this application is based on the results of the phase iii clarity ad study and the phase iib clinical study (study 201), which demonstrated that lecanemab treatment showed a reduction of clinical decline in early ad.

lecanemab selectively binds and eliminates soluble, toxic aβ aggregates (protofibrils) that are thought to contribute to the neurotoxicity in ad. as such, lecanemab may have the potential to have an effect on disease pathology and to slow down the progression of the disease. the clarity ad study of lecanemab met its primary endpoint and all key secondary endpoints with highly statistically significant results. in november 2022, the results of the clarity ad study were presented at and simultaneously published in , a peer-reviewed medical journal.

in the u.s., lecanemab was granted accelerated approval as a treatment for ad by the u.s. food and drug administration (fda) on january 6, 2023. on the same day, eisai submitted a supplemental biologics license application (sbla) to the fda for approval under the traditional pathway. in europe, eisai submitted a marketing authorization application (maa) to the european medicines agency (ema) on january 9, 2023 and accepted on january 26, 2023. in china, eisai initiated submission of data for a bla to the national medical products administration (nmpa) in december 2022.

eisai serves as the lead of lecanemab development and regulatory submissions globally with both eisai and biogen co-commercializing and co-promoting the product and eisai having final decision-making authority.

accelerated approval is based on phase 2 data showing a reduction in amyloid-beta plaques in early ad patients treated with leqembi™

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

tokyo and cambridge, mass., january 7, 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 today that under the accelerated approval pathway the u.s. food and drug administration (fda) has approved lecanemab–irmb (brand name in the u.s.: leqembi™) 100 mg/ml injection for intravenous use, a humanized immunoglobulin gamma 1 (igg1) monoclonal antibody directed against aggregated soluble (“protofibril”)* and insoluble forms of amyloid beta (aβ) for the treatment of alzheimer’s disease (ad). the approval is based on phase 2 data that demonstrated that leqembi reduced the accumulation of aβ plaque in the brain, a defining feature of ad. using the recently published data from the large global confirmatory phase 3 clinical trial, clarity ad, eisai will work quickly to file a supplemental biologics license application (sbla) to the fda for approval under the traditional pathway.

indication
leqembi is indicated for the treatment of alzheimer’s disease. 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 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 a confirmatory trial.

dosage and administration (patient selection, dosing instructions, monitoring and dosing interruption for aria)
the recommended dosage of leqembi is 10 mg/kg administered intravenously once every two weeks to eligible patients with confirmed presence of aβ pathology prior to initiating treatment. enhanced clinical vigilance for amyloid–related imaging abnormalities (aria) is recommended during the first 14 weeks of treatment with leqembi. baseline, recent (within one year) brain mri prior to initiating treatment with leqembi and periodic monitoring with mri prior to the 5th, 7th, and 14th infusions should be obtained.

adverse reactions
the safety of leqembi has been evaluated in 763 patients who received at least one dose of leqembi in study 201. the most common adverse reactions reported in at least 5% of patients treated with leqembi 10 mg/kg biweekly (n=161) and at least 2% higher incidence than patients on placebo (n=245) were infusion–related reactions (leqembi 20%; placebo 3%), headache (leqembi 14%; placebo 10%), ariae (leqembi 10%; placebo 1%), cough (leqembi, 9%; placebo, 5%) and diarrhea (leqembi, 8%; placebo, 5%). the most common adverse reaction leading to discontinuation of leqembi was infusionrelated reactions that led to discontinuation in 2% (4/161) of patients treated with leqembi compared to 1% (2/245) of patients on placebo.

“the fda’s approval of leqembi under the accelerated approval pathway is an important milestone in eisai’s four decades of research in alzheimer’s disease and reflects our continued commitment to alleviating the burden of alzheimer’s disease for patients and their families. eisai has made great efforts to understand the reality of the challenges and concerns facing patients and their families who are living in the various stages of alzheimer’s disease, and we are incredibly pleased to offer leqembi as a new treatment option to help with the tremendous unmet needs of this community,” said haruo naito, chief executive officer at eisai co., ltd. “the challenges of alzheimer’s disease reach beyond medical implications for patients and considerations for their families, but also impact society as a whole through reduced productivity, elevated social costs and anxiety. upon receiving this accelerated approval, we will focus on providing important information on proper usage of leqembi to healthcare professionals. eisai will also engage with various payers to provide access to leqembi, offer a patient support program, and
will do its utmost to complete submission for traditional approval as soon as possible to serve more people living with early alzheimer’s disease.”

“the approval of leqembi provides new hope to patients with alzheimer’s disease. patients at an early stage of the disease and their caregivers can now consider a new treatment option with their doctors. our focus now is on the path forward, working alongside eisai with the goal of making leqembi available to patients who may benefit from this treatment as soon as possible,” said christopher a. viehbacher, president and chief executive officer of biogen. “this approval is also a recognition of the many scientists and doctors who have, over many years, patiently and persistently worked to find a treatment for this highly complex disease. eisai and biogen have collaborated for nearly a decade to advance research to improve the lives of those suffering from alzheimer’s, and we know that this commitment must and will continue in the fight against alzheimer’s disease.”

media contacts:
eisai co., ltd.
public relations department
tel: 81 (0)3–3817–5120

eisai inc. (u.s.)
libby holman
1–201–753–1945
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

biogen inc.
natacha gassenbach
1–857–777–6573
public.affairs@biogen.com

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

tokyo and osaka, december 22, 2022  – astellas pharma inc. (tse: 4503, president and ceo: kenji yasukawa, “astellas”), eisai co., ltd. (tse: 4523, ceo: haruo naito, “eisai”), daiichi sankyo company, limited (tse: 4568, president : sunao manabe, “daiichi sankyo”) and takeda pharmaceutical company limited. (tse: 4502 / nyse:tak, president and ceo christophe weber, “takeda”) today announced that the four companies have agreed the collaboration to reduce environmental burden in the field of pharmaceutical packaging.

based on the agreement, the four companies will aim to promote the use of more environmentaly friendly packaging for pharmaceutical products by sharing knowledge on packaging technologies to reduce environmental burden, such as blister packs made of biomass-based plastic instead of petroleum-derived plastic, compact packaging, recycled packaging materials, and recyclable packaging materials.

astellas, eisai, daiichi sankyo, and takeda aim to ensure that society benefits from this collaboration to harmonize corporate activities with the global environment. in the future, the four companies expect to expand this collaboration beyond the four companies by calling on other companies in order to reduce further environmental burden.

■  initiatives for sustainability (environment) of each company

astellas has set “deepen our engagement in sustainability” as one of the strategic goals in its . the reduction of environmental burden is one of astellas’ priority themes within sustainability. for more information on specific initiatives, please visit .

eisai established the “eisai environmental management vision” this fiscal year, and in addition to climate change countermeasures aimed at achieving carbon neutrality by fiscal 2040, eisai has formed a medium- to long-term plan for environmental issues including efficient use of water and recycling of resources, and will work to further advance these efforts. to learn more about our environmental initiatives, please visit .

as a healthcare company with the purpose “to contribute to the enrichment of quality of life around the world,” daiichi sankyo considers global environmental conservation, which is the basis of life and livelihood, as a key management issue () and promotes environmental management. for more information on specific initiatives, please visit .

at takeda, “purpose-led sustainability” is about creating both business and societal value through its core business. takeda continues to reduce our operational carbon footprint and are now committed to achieving net-zero ghg emissions for scopes 1 and 2 before 2035 and for scope 3 before 2040. for more information, see our .

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that eisai and washington university school of medicine in st. louis have entered into a comprehensive research collaboration agreement aiming to create potential novel treatments for neurodegenerative disorders, including alzheimer’s disease (ad) and parkinson’s disease (pd).

washington university is world leading in research on prevention, diagnosis, biomarkers and treatment of neurodegenerative diseases. the two organizations have been collaborating in ad research. the phase ii/iii tau nexgen study conducted by the dominantly inherited alzheimer network trials unit (dian-tu), led by the university’s school of medicine, is exploring the safety, tolerability, biomarkers and cognitive efficacy of eisai’s anti-mtbr (microtubule binding region) tau antibody e2814 for the treatment of dominantly inherited alzheimer’s disease (diad). in this study, the anti-amyloid beta (aβ) protofibril antibody lecanemab (generic name, development code: ban2401) was selected as the background anti-amyloid agent.

the collaboration strategically combines washington university scientists’ expertise in the fundamental and clinical research in neurodegenerative diseases, such as dementia, with eisai’s extensive experience in drug discovery and development. using human biology, the aim is to create multiple novel therapeutic candidates as well as discover and identify biomarkers within the next five years. eisai will have the option rights to develop and commercialize any compounds and biomarkers that meet certain criteria in terms of research and development milestones. in the case that eisai chooses to exercise the options, eisai will pay washington university milestone payments and royalties on future sales of each licensed compounds.

dr. teiji kimura, ph.d., academia and industry alliance officer, deep human biology learning (dhbl) office of eisai, commented, “patients living with neurodegenerative diseases, including alzheimer’s disease and parkinson’s disease, struggle with critical unmet medical needs, which is the reason neurology is a key therapeutic area for eisai. by collaborating with world-leading research institutions such as washington university in st. louis, eisai is working to fulfill our human health care mission and provide potential new and targeted disease-modifying therapies with the ultimate goal of achieving a world free of neurodegenerative disease.”

media inquiries:

public relations department, eisai co., ltd.

81-(0)3-3817-5120

eisai inc (u.s.)

libby holman　201-753-1945

tokyo and cambridge, 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 results from eisai’s large global phase 3 confirmatory clarity ad clinical study of lecanemab (development code: ban2401), an investigational anti-amyloid beta (aβ) protofibril antibody for the treatment of mild cognitive impairment (mci) due to alzheimer’s disease (ad) and mild ad (collectively known as early ad) with confirmed presence of amyloid pathology in the brain, were presented at the 2022 clinical trials on alzheimer’s disease (ctad) conference, in san francisco, california and virtually.

summary of presentations in the scientific session featuring lecanemab at ctad

design of clarity ad study

eisai’s clarity ad was a global confirmatory phase 3 placebo-controlled, double-blind, parallel-group, randomized study in 1,795 people with early ad (lecanemab group: 898 placebo group: 897) at 235 sites in north america, europe, and asia. the participants were randomized 1:1 to receive either placebo or lecanemab 10-mg/kg iv biweekly, and the randomization was stratified according to clinical subgroup (mci due to ad or mild ad), presence or absence of concomitant approved ad symptomatic medication at baseline (e.g., acetylcholinesterase inhibitors, memantine, or both), apoe4 status and geographical region. eligibility criteria allowed patients with a broad range of comorbidities/comedications, including but not limited to hypertension, diabetes, heart disease, obesity, renal disease and anti-coagulants. as a result of eisai’s recruitment strategy of diversity in the clarity ad study, 4.5% and 22.5% of the randomized participants in the u.s. were black and hispanic, respectively.

the primary endpoint was change from baseline at 18 months in the cdr-sb¹ (clinical dementia rating sum of boxes), the global cognitive and functional scale, and key secondary endpoints were the change from baseline at 18 months in amyloid positron emission tomography (pet) using centiloids, ad assessment scale – cognitive subscale 14 (adas-cog14²), ad composite score (adcoms³) and ad cooperative study-activities of daily living scale for mild cognitive impairment (adcs mci-adl⁴). in addition, longitudinal changes in brain tau pathology as measured by tau pet (n=257) and cerebrospinal fluid (csf) biomarkers of ad pathology (n=281) were evaluated in optional sub-studies.

efficacy results of clarity ad

mean change of cdr-sb from baseline at 18 months as the primary endpoint was 1.21 and 1.66 for lecanemab and placebo groups, respectively. lecanemab treatment resulted in highly statistically significant results, reducing clinical decline on the global cognitive and functional scale, compared with placebo at 18 months by -0.45 (95% confidence interval (ci): -0.67, -0.23; p=0.00005), representing a 27% slowing of decline. starting as early as six months (difference: -0.17 [95% ci: -0.29, -0.05]; p<0.01), and increasing in absolute difference over time across all time points every 3 months, the treatment showed highly statistically significant changes in cdr-sb from baseline compared to placebo (all p-values are less than 0.01) (figure 1).

all key secondary endpoints also showed highly statistically significant results compared with placebo (p<0.001). in the amyloid pet sub-study, treatment with lecanemab showed statistically significant reduction in amyloid plaque burden at all timepoints starting at 3 months. mean change in centiloids at 18 months was -55.5 and 3.6 for lecanemab and placebo groups, respectively (mean difference: -59.1 [95%ci: -62.6, -55.6]; p<0.00001). lecanemab slowed decline of cognitive function by 26% on adas-cog14 at 18 months (mean difference: -1.44 [95%ci: -2.27, -0.61]; p=0.00065). in the adcoms assessment, lecanemab slowed disease progression by 24% at 18 months (mean difference: -0.050 [95% ci: -0.074, 　-0.027; p=0.00002]). lecanemab slowed decline of activities of daily living by 37% on adcs mci-adl at 18 months (mean difference: 2.016 [95%ci: 1.208, 2.823]; p<0.00001). in addition, the primary stratified analysis showed consistent results in cdr-sb, adas-cog14 and adcs mci-adl at 18 months of treatment with lecanemab in all subgroups of disease stage (mci due to ad or mild ad), apoe4 status (non-carriers, carriers), presence or absence of concomitant approved ad symptomatic medication, and region (north america, asia, europe).

figure1. cdr-sb as primary endpoint change (18 months)

safety results of clarity ad

the most common adverse events (>10%) in the lecanemab group were infusion reactions (lecanemab: 26.4%; placebo: 7.4%), aria-h (combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis; lecanemab: 17.3%; placebo: 9.0%), aria-e (edema/effusion; lecanemab: 12.6%; placebo: 1.7%), headache (lecanemab: 11.1%; placebo: 8.1%), and fall (lecanemab: 10.4%; placebo: 9.6%). infusion reactions were largely mild-to-moderate (grade 1-2: 96%) and occurred on the first dose (75%).

during the study period, deaths occurred in 0.7% and 0.8% of participants in the lecanemab and placebo groups, respectively and no deaths were related to lecanemab or occurred with amyloid-related imaging abnormalities (aria) in 18-month double-blind study period. serious adverse events were experienced by 14.0% of participants in the lecanemab group and 11.3% of participants in the placebo group. treatment-emergent adverse events occurred in 88.9% and 81.9% of participants in the lecanemab and placebo groups, respectively. treatment-emergent adverse events leading to drug withdrawal occurred in 6.9% and 2.9% of participants in the lecanemab and placebo groups, respectively.

overall, lecanemab’s aria incidence profile was within expectations based on the phase 2 trial results. aria-e events were largely mild-to-moderate radiographically (91% of those who had aria-e), asymptomatic (78% of those who had aria-e), occurred within the first 3 months of treatment (71% of those who had aria-e) and resolved within 4 months of detection (81% of those who had aria-e). among the 2.8% of lecanemab-treated subjects with symptomatic aria-e, the most commonly reported symptoms were headache, visual disturbance, and confusion. the incidence of symptomatic aria-h was 0.7% in the lecanemab group and 0.2% in the placebo group. no imbalance was observed in isolated aria-h (i.e., aria-h in participants who did not also experience aria-e) between lecanemab (8.9%) and placebo (7.8%). aria-e and aria-h were less common in apoe4 non-carriers versus carriers, with higher frequency in apoe4 homozygous carriers vs apoe4 heterozygous carriers. in the core study and subsequent open-label extension study, rates of deaths with concurrent cerebral macrohemorrhage were 0.1% in both the placebo group (1/897) and the lecanemab group (2/1608). the two cases on lecanemab occurred in the open-label extension study. both cases had significant comorbidities and risk factors including anticoagulation contributing to macrohemorrhage or death. therefore, it is eisai’s assessment that the deaths cannot be attributed to lecanemab.

imaging, plasma, and csf biomarkers assessments of clarity ad

biomarkers assessments on amyloid, tau and neurodegeneration with lecanemab administration were conducted using imaging, plasma and csf. amyloid biomarkers showed early and sustained amyloid reversal effects in csf and plasma aβ 42/40 ratio with lecanemab treatment. mean amyloid pet was 22.99 centiloids at 18 months of lecanemab treatment which was below threshold for amyloid positivity of 30 centiloids. tau biomarkers showed that removing amyloid improved csf and plasma p-tau (p-tau181), downstream of amyloid in the ad pathology pathway. tau pet analysis showed that lecanemab treatment slowed tau accumulation in the temporal lobe as well as improved total tau (t-tau) in compared to the placebo. as for biomarkers of neurodegeneration, lecanemab improved glial fibrillary acidic protein (gfap) in plasma, a marker of astrocyte activation, and neurogranin in csf, a marker of synaptic dysfunction, improved to normal levels by treatment, while there was no significant difference in neurofilament light chains in csf or plasma between lecanemab and placebo.

clarity ad results in context

ad is a progressive neurological disorder that severely impacts people living with the condition and their loved ones. with the increased global aging population, ad has become a critical issue for society and healthcare systems. new therapeutic agents that act on the disease pathology are needed. the treatment goals for early ad are to have sustained effects on cognitive function, activities of daily living and psychiatric symptoms, to maintain independence longer by slowing progression of the disease and to improve or maintain quality of life.

in eisai’s confirmatory clarity ad study, lecanemab demonstrated consistency of results across scales of cognition and function and subgroups (race, ethnicity, comorbidities). lecanemab treatment showed 31% lower risk of converting to next stage of disease by global cdr assessment (hazard ratio: 0.69). a slope analysis using cdr-sb based on observed data and extrapolation to 30 months showed that lecanemab takes 25.5 months to reach same level as placebo at 18 months, indicating a 7.5 month slowing of progression. modeling simulations based on the phase 2 trial data suggest that lecanemab may slow the rate of disease progression by 2.5-3.1 years and has the potential to help people remain in the earlier stages of ad for a longer period of time. in addition, it was shown to maintain the health-related quality of life and reduce the burden on caregivers (23-56% reduction in score worsening). the convergence of evidence across cognition and function, disease progression, health related quality of life, and caregiver burden demonstrate that lecanemab treatment may provide meaningful benefits to patients, their care partners, physicians and society.

eisai is hosting a live webcast of the scientific session featuring the lecanemab presentations, which can be viewed live on . the content will be available on demand afterward.

eisai serves as the lead of lecanemab development and regulatory submissions globally with both eisai and biogen co-commercializing and co-promoting the product and eisai having final decision-making authority.

this release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. there is no guarantee that such an investigational agent will successfully gain health authority approval.

¹ cdr-sb is a numeric scale used to quantify the various severity of symptoms of dementia. based on interviews of people living with ad and family/caregivers, qualified healthcare professionals assess cognitive and functional performance in six areas: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. the total score of the six areas is the score of cdr-sb, and cdr-sb is also used as an appropriate item for evaluating the effectiveness of therapeutic drugs targeting the early stages of ad.

² adas-cog is the most common cognitive assessment instrument used in ad clinical trials all over the world. adas-cog14 consists of 14 competencies: word recall, commands, constructional praxis, object and finger naming, ideational praxis, orientation, word recognition, remembering word recognition instructions, comprehension of spoken language, word finding difficulty, spoken language ability, delayed word recall, number cancellation, and maze task. adas-cog has been used in clinical trials for earlier stages of ad including mci.

³ developed by eisai, adcoms combines items from the adas-cog scale for assessing cognitive functions, mmse and the cdr scale for evaluating the severity of dementia to enable highly sensitive detection of changes in clinical functions of early ad symptoms and changes in memory

⁴ adcs mci-adl assesses the competence of patients with mci in activities of daily living (adls), based on 24 questions to the patient’s partner about actual recent activities of daily living.