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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

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that new study results on its in-house discovered and developed anticancer agent eribulin mesylate (halaven^®, “eribulin”) will be presented during the 2022 san antonio breast cancer symposium (sabcs), which is taking place virtually and in-person in san antonio, texas from december 6-10.

eisai will present five eribulin-related abstracts, including a post hoc subgroup analysis from two pivotal phase 3 studies (embrace and study 301), as well as:

– real world use of eribulin following treatment with a p13k inhibitor, mostly in people with hormone receptor (hr)-positive/her2-negative metastatic breast cancer.

– preclinical data exploring a liposomal formulation of eribulin, in a phase 1 expansion cohort for breast cancer, versus eribulin at the same dose, in patient-derived breast cancer xenografts.

“we continue to relentlessly pursue research that provides useful insights for people living with breast cancer,” said dr. takashi owa, chief scientific officer, senior vice president, eisai co., ltd. “a big part of this commitment is the ongoing sharing of our preclinical and clinical data with eribulin.”

this release discusses investigational compounds and investigational uses for fda-approved products. it is not intended to convey conclusions about efficacy and safety. there is no guarantee that any investigational compounds or investigational uses of fda-approved products will successfully complete clinical development or gain fda approval.

eisai presentations at the 2022 sabcs are as follows:

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.

eisai co., ltd. (headquarters: toyoko, ceo: haruo naito, “eisai”) will present the efficacy, safety and biomarker findings from the company’s phase 3 confirmatory clarity ad clinical trial for lecanemab (development code: ban2401), an investigational anti-amyloid beta (aβ) protofibril antibody for the potential 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, at the 15th clinical trials on alzheimer’s disease (ctad) conference. at the meeting, which will be held in san francisco, ca and virtually from november 29 to december 2, eisai and esteemed faculty will present the full data in a scientific session on the first day of the meeting (november 29 at 4:50 p.m. pt). additionally, other important research from the lecanemab clinical development program and eisai’s ad pipeline, including the company’s investigational anti-microtubule binding region (mtbr) tau antibody (e2814), will be presented in four oral and ten poster presentations.

topline results from clarity ad were announced in late september and showed that lecanemab 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.

key eisai lecanemab ctad presentations

clarity ad: full results from the phase 3 confirmatory clarity ad clinical trial of lecanemab in patients with early ad will be presented in a scientific session on november 29 at 4:50 p.m. pt. eisai will host a live webcast of presentations in the session and can be viewed live on the of the eisai co., ltd. website.
aβ protofibrils binding properties: research studying the characterization of aβ protofibrils and the unique binding properties and mechanisms of aβ clearance of lecanemab (poster #p029)
ahead 3-45 study:
〇 an evaluation of tau pet screening data from the phase 3 ahead 3-45 study of lecanemab for associations with plasma p-tau217 and cognitive testing (late breaker oral #lb1)

〇 a study exploring increased accuracy of amyloid pet prediction in preclinical ad using plasma levels for abeta42/40 and p-tau217 ratios from the phase 3 screening data from the ahead 3-45 study (late breaker oral #lb2)

“based on the clarity ad results, the investigational anti-amyloid beta protofibril antibody lecanemab has the potential to make a clinically meaningful difference for people living with the early stages of alzheimer’s disease and their families by slowing cognitive and functional decline,” said lynn kramer, m.d., chief clinical officer, alzheimer’s disease and brain health at eisai co., ltd. “eisai is excited to share the results of the company’s confirmatory phase 3 clarity ad clinical study at ctad and present important data exploring lecanemab’s potential efficacy, safety and use in a variety of early ad patient sub-populations.”

eisai aims to file for traditional approval in the u.s. and for marketing authorization applications in japan and europe by the end of eisai’s fy2022, which ends march 31, 2023. in july 2022, the u.s. food and drug administration (fda) accepted eisai’s biologics license application (bla) for lecanemab under the accelerated approval pathway and granted it priority review. the prescription drug user fee act (pdufa) action date is january 6, 2023. the fda has agreed that the results of clarity ad can serve as the confirmatory study to verify the clinical benefit of lecanemab. in an effort to secure traditional fda approval for lecanemab as soon as possible, eisai submitted the bla through the fda’s accelerated approval pathway so that the agency could complete its review of all lecanemab data with the exception of the data from the confirmatory clarity ad study. in march 2022, eisai began submitting application data, with the exception of clarity ad data, to japan’s pharmaceuticals and medical devices agency (pmda) under the prior assessment consultation system, with the aim of obtaining early approval for lecanemab so that people living with early ad may have access to the therapy as soon as possible.

ctad 2022 presentations relating to eisai’s key compounds, research and collaborations

scientific session: clarity ad: a phase 3 placebo-controlled, double-blind, parallel-group, 18-month study evaluating lecanemab in early alzheimer’s disease tues, nov 29, 4:50 – 6:05 p.m. pt
chairman: takeshi iwatsubo, university of tokyo
clarity ad: clinical trial background and study design overview	michael irizarry eisai inc.
lecanemab for the treatment of early alzheimer’s disease: topline efficacy results from clarity ad	christopher van dyck yale school of medicine
safety profile of lecanemab in early alzheimer’s disease	marwan sabbagh barrow neurological institute
imaging, plasma and csf biomarkers assessments from clarity ad	randall bateman washington university
context of clarity ad results	sharon cohen toronto memory program
panel discussion / q&a

oral presentations

asset in development, session, time (pacific time)	presentation title, presenter/authors
lecanemab session: late breaking oral communications: #lb1 wed, nov 30 session time: 10:30 – 11:00 a.m. presentation time: 10:30 – 10:45 a.m.	tau pet associated with plasma p-tau217 and cognitive testing in preclinical ad: screening data from the ahead study a3 and a45 trials presenter: k johnson authors: k johnson, et al
lecanemab session: late breaking oral communications: #lb2 wed, nov 30 session time: 10:30 – 11:00 a.m. presentation time: 10:45 – 11:00 a.m.	plasma levels of abeta42/40 and p-tau217 ratios increase accuracy of amyloid pet prediction in preclinical ad presenter: r rissman authors: r rissman, et al
e2814 session: late breaking oral communications: #lb4 wed, nov 30 session time: 3:00 – 3:45 p.m. presentation time: 3:15 p.m. – 3:30 p.m.	csf mtbr-tau243 is a non-amyloid specific biomarker of neurofibrillary tangles of alzheimer’s disease presenter: k horie authors: k horie, et al
e2027 session: oral communications: #oc2 wed, nov 30 session time: 11:00 a.m. – 12:15 p.m. presentation time: 11:15 – 11:30 a.m.	results of a phase 2/3 placebo-controlled, double-blind, parallel-group, randomized study to evaluate the efficacy and safety of 12 week treatment with the phosphodiesterase 9 (pde9) inhibitor irsenontrine (e2027) in subjects with dementia with lewy bodies presenter: m irizarry authors: m irizarry, et al

asset in development, session, time (pacific time)

presentation title, presenter/authors

lecanemab
session: late breaking oral communications: #lb1
wed, nov 30
session time: 10:30 – 11:00 a.m.
presentation time: 10:30 – 10:45 a.m.

tau pet associated with plasma p-tau217 and cognitive testing in preclinical ad: screening data from the ahead study a3 and a45 trials
presenter: k johnson

authors: k johnson, et al

lecanemab
session: late breaking oral communications: #lb2
wed, nov 30
session time: 10:30 – 11:00 a.m.

presentation time: 10:45 – 11:00 a.m.

plasma levels of abeta42/40 and p-tau217 ratios increase accuracy of amyloid pet prediction in preclinical ad
presenter: r rissman

authors: r rissman, et al

e2814
session: late breaking oral communications: #lb4
wed, nov 30
session time: 3:00 – 3:45 p.m.
presentation time: 3:15 p.m. – 3:30 p.m.

csf mtbr-tau243 is a non-amyloid specific biomarker of neurofibrillary tangles of alzheimer’s disease
presenter: k horie

authors: k horie, et al

e2027
session: oral communications:
#oc2
wed, nov 30
session time: 11:00 a.m. – 12:15 p.m.

presentation time: 11:15 – 11:30 a.m.

results of a phase 2/3 placebo-controlled, double-blind, parallel-group, randomized study to evaluate the efficacy and safety of 12 week treatment with the phosphodiesterase 9 (pde9) inhibitor irsenontrine (e2027) in subjects with dementia with lewy bodies
presenter: m irizarry

authors: m irizarry, et al

poster presentations

asset in development, session, time (pacific time)	presentation title, authors
lecanemab session: clinical trials methodology: #p012 tues, nov 29, 4:00 p.m. – wed, nov 30, 6:00 p.m.	development and feasibility of a data-driven approach to preclinical alzheimer’s disease clinical trial recruitment through centralized pre-screening data collection authors: d kirn, et al
lecanemab session: new therapies and clinical trials: #p029 tues, nov 29, 4:00 p.m. – wed, nov 30, 6:00 p.m.	characterization of amyloid-beta protofibrils in alzheimer’s disease brain and the unique binding properties of lecanemab authors: l lannfelt, et al
e2027 session: clinical trials results: #p048 tues, nov 29, 4:00 p.m. – wed, nov 30, 6:00 p.m.	the effects of the novel phosphodiesterase 9 (pde9) inhibitor e2027 (irsenontrine) on csf cgmp, additional csf and plasma biomarkers, and clinical outcomes in amyloid positive and amyloid negative patients with dementia with lewy bodies and parkinson’s disease dementia authors: p sachdev, et al
general ad session: clinical trials results: #p037 tues, nov 29, 4:00 p.m. – wed, nov 30, 6:00 p.m.	planning the next generation of alzheimer’s disease clinical trials using diverse patient-level database from the critical path for alzheimer’s disease (cpad) consortium authors: s sivakumaran, et al
general ad session: clinical trials results: #p038 tues, nov 29, 4:00 p.m. – wed, nov 30, 6:00 p.m.	critical path for alzheimer’s disease (cpad) consortium: accelerating and de-risking therapeutic development in ad by building regulatory decision-making tools authors: s sivakumaran, et al
general ad session: clinical trials biomarkers including plasma: #lp66 thu, dec 1, 8:00 a.m. – 6:00 p.m.	baseline plasma ptau181 improves prediction of cognitive decline in amyloid positive subjects with mild cognitive impairment authors: v devanarayan, et al
general ad session: epidemiology and clinical trials: #p176 fri, dec 2, 8:00 a.m. – 5:00 p.m.	identification of medical conditions as risk factors for mild cognitive impairment: a us claims database study authors: g li, et al
general ad session: epidemiology and clinical trials: #p184 fri, dec 2, 8:00 a.m. – 5:00 p.m.	prevalence estimations for the alzheimer’s disease continuum in the us health and retirement study authors: a abbas tahami monfared, et al
general ad session: cognitive and functional endpoints: #p139 (virtual only) thu, dec 1, 8:00 a.m. – 6:00 p.m.	dementia conversion rate differences between patients with high- and low-risk amnestic mild cognitive impairment in the real-world: a prospective, multicenter, observational study authors: h jang, et al

sysmex poster presentation

asset in development, session, time (pacific time)	presentation title, authors
general ad session: clinical trials biomarkers including plasma: #lp84a thu, dec 1, 8:00 a.m. – 6:00 p.m.	three group classification of participants based on fully automated plasma β-amyloid measurements to achieve high positive and negative predictive values authors: k yamashita, et al

asset in development, session, time (pacific time)

presentation title, authors

general ad
session: clinical trials biomarkers including plasma: #lp84a

thu, dec 1, 8:00 a.m. – 6:00 p.m.

three group classification of participants based on fully automated plasma β-amyloid measurements to achieve high positive and negative predictive values

authors: k yamashita, et al

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 agents in development and is not intended to convey conclusions about efficacy or safety. there is no guarantee that such investigational agents will successfully complete clinical development or gain health authority approval.

media inquiries:

eisai co., ltd.

public relations department,

81-(0)3-3817-5120

eisai inc. (u.s.)

libby holman

1-201-753-1945

eisai europe, ltd. (europe, australia, new zealand and russia)

emea communications department

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that it has received notification from japan’s ministry of health, labour, and welfare (mhlw) that the “all-case study” specified post-marketing observational study condition required at the time of approval of antiepileptic agent inovelon^® tablets 100 mg and 200 mg (rufinamide) as an adjunctive therapy to other antiepileptic drugs (aeds) for treatment of lennox-gastaut syndrome (lgs) has been cleared.

in march 2013, the mhlw approved inovelon as an adjunctive therapy with other antiepileptic drugs for tonic and atonic seizures associated with lgs showing insufficient response to other antiepileptics, with the following condition: “because of the very limited number of subjects included in the japanese clinical trials, the applicant is required to conduct a post-marketing observational study in all patients until data from a certain number of patients is accumulated after its launch in the market, in order to identify the background information of patients treated with the product and collect safety and efficacy data on the product in the early post-marketing period, and thereby take necessary measures to ensure proper use of the product.”

based on the safety data in 702 patients and efficacy data in 495 patients submitted to the mhlw as the results of analyses of this all-case study, the mhlw has concluded that the all-case study was conducted properly and the necessary measures to ensure proper use of the product were sufficient to lift the condition.

eisai will continually strive to promote the proper use of inovelon and provide information about the product, thereby making further contributions to increase the benefits to patients and their families.

media inquiries:

public relations department,

eisai co., ltd.

81-(0)3-3817-5120

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that it has received notification that aricept^® (donepezil hydrochloride), a treatment for alzheimer’s disease and dementia with lewy bodies that was discovered and developed in-house, has been granted category 2* status based on the results of a reexamination of its efficacy, dosage and administration for the treatment of dementia with lewy bodies (dlb) in japan. in conjunction with this, eisai plans to promptly submit an application for a partial change to label regarding dosage and administration. the indication for dlb remains unchanged.

the indication of “suppression of progression of dementia symptoms in dlb” was approved in september 2014, primarily based on a phase ii study (study 431) and phase iii study (study 341) conducted by eisai on people living with dlb in japan. in accordance with the condition for the approval of this indication, “a clinical trial to verify the efficacy and safety of the drug in patients with dlb should be conducted and the results of the trials and analyses should be submitted promptly after completion,” eisai conducted a post-marketing clinical study (study 419) to evaluate the efficacy and safety of the drug in patients with dlb.

the results of study 419 did not show a statistically significant difference between the placebo group and the aricept group in the primary endpoint of global function (cibic-plus** comprehensive assessment), but the re-examination based on post-marketing studies, including the results of study 419, stated that “at present, the evaluation of clinical function in dlb using cibic-plus is not always sufficiently established as an evaluation method, and it is difficult to comprehensively evaluate the efficacy of this drug for dlb, although efficacy was seen in some patients. on the other hand, treatment with this drug showed a trend toward improvement in cognitive function (mmse***), and this result is consistent with the results of the clinical trial at the time of approval of the drug. since there are a certain number of patients who can be expected to benefit from the administration of this drug, it was concluded that the efficacy should be evaluated after the start of administration, and administration should only continue if efficacy is confirmed.”

therefore, it was concluded that the approved label (dose and administration) and package insert should be appropriately revised (category 2).

the condition of the approval was lifted as of the date of receipt of the reexamination results.

along with this prompt application for a partial change to label regarding dosage and administration for the dlb indication, eisai will place the highest priority on the provision of proper use and safety information for this drug, and will make continued contributions to address the diversified needs of, and increase the benefits provided to people living with dlb and their families.

media inquiries:

public relations department,

eisai co., ltd.

81-(0)3-3817-5120

* category 2: partial changes in approval (modifications in approved items as directed)

** cibic-plus (the clinician’s interview-based impression of change plus caregiver input): a validated clinical instrument used to measure change in global function through an interview with patients and their caregivers. patients are evaluated by an assessor who is independent from the attending physician on a 7-point scale (very much improved, much improved, minimally improved, no change, minimally worse, much worse and very much worse) in four major categories: general, mental/cognitive state, behavior, and activities of daily living.

*** mmse (mini-mental state examination): a method for assessing cognitive function. comprised of the categories orientation, memorization, attention, calculation, recent and distant memory, comprehension, reading and writing, as well as design. test scores range from 30 (normal) to 0 (severely impaired).

to strengthen its research and development function for injectable drug formulations

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that, as part of the strategic investment towards the realization of its medium-term business plan “eway future & beyond”, it has completed construction of the new injection/research building “eisai medicine innovation technology solutions” (“emits”) at the kawashima industrial park located in gifu prefecture, japan.

emits will be eisai’s global base for formulation and modality research. in recent years, eisai’s drug discovery targets have expanded to include modalities such as antibodies, antibody drug conjugates (adcs), and nucleic acid drugs, in addition to conventional small molecule compounds. at emits, eisai will strengthen its injectable drug formulation development research function and drug delivery system (dds) development function, including liposomal and lipid nanoparticle formulations, and address the development of various modalities. the following initiatives will be implemented.

elevating the quality and speed of formulation process research through introduction of a state-of-the-art manufacturing data management system and utilization of ai
installation of facilities that also enable the manufacturing of clinical trial materials in order to manufacture investigational injection drugs in-house
introduction of rapid microbial testing methods for advanced microbiological control and sterility assurance
enhancing collaboration with the creation of flexible space that can also be used for collaborative research with external partners and technologies

through these efforts, eisai aims to elevate the quality of the technology and knowledge of its formulation research function, and to become a base for disseminating innovation, technology, and solutions relating to formulations. the aggregate investment in the construction of emits is approximately 10 billion japanese yen.

the kawashima industrial park is eisai’s global pharmaceutical manufacturing base, at which eisai has made a comprehensive framework comprising all steps from formulation research to formulation manufacturing. through the construction of emits, eisai aims to elevate the quality of its formulation research and formulation manufacturing, accelerate medicine creation activities, and ultimately further its contribution to improving the benefits of patients and their families.

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eisai co., ltd.

81-(0)3-3817-5120

· all key secondary endpoints also met, demonstrating highly statistically significant results

· profile of amyloid-related imaging abnormalities (aria) incidence was within expectations

· eisai aims to file for traditional approval in the u.s., and to submit marketing authorization applications in japan and europe by the end of eisai fy2022, which ends on march 31, 2023

tokyo and cambridge, eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) and biogen inc. (nasdaq: biib, corporate headquarters: cambridge, massachusetts, ceo: michel vounatsos, “biogen”) announced positive topline results from eisai’s large global phase 3 confirmatory clarity ad clinical trial 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. lecanemab met the primary endpoint (cdr-sb: clinical dementia rating-sum of boxes*) and all key secondary endpoints with highly statistically significant results. eisai will discuss this data with regulatory authorities in the u.s., japan and europe with the aim to file for traditional approval in the us and for marketing authorization applications in japan and europe by the end of eisai’s fy2022, which ends march 31, 2023. additionally, eisai will present the clarity ad study results on november 29, 2022, at the clinical trials on alzheimer’s congress (ctad), and publish the findings in a peer-reviewed medical journal.

* 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.

lecanemab treatment met the primary endpoint and reduced clinical decline on the global cognitive and functional scale, cdr-sb, compared with placebo at 18 months by 27%, which represents a treatment difference in the score change of -0.45 (p=0.00005) in the analysis of intent-to-treat (itt) population. starting as early as six months, across all time points, the treatment showed highly statistically significant changes in cdr-sb from baseline compared to placebo (all p-values are less than 0.01). all key secondary endpoints were also met with highly statistically significant results compared with placebo (p<0.01). key secondary endpoints were the change from baseline at 18 months compared with placebo of treatment in amyloid levels in the brain measured by amyloid positron emission tomography (pet), the ad assessment scale-cognitive subscale14 (adas-cog14), ad composite score (adcoms) and the ad cooperative study-activities of daily living scale for mild cognitive impairment (adcs mci-adl).

the incidence of amyloid-related imaging abnormalities-edema/effusion (aria-e), an adverse event associated with anti-amyloid antibodies, was 12.5% in the lecanemab group and 1.7% in the placebo group. the incidence of symptomatic aria-e was 2.8% in the lecanemab group and 0.0% in the placebo group. the aria-h (aria cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis) rate was 17.0% in the lecanemab group and 8.7% in the placebo group. the incidence of symptomatic aria-h was 0.7% in the lecanemab group and 0.2% in the placebo group. there was no imbalance in isolated aria-h (i.e., aria-h in patients who did not also experience aria-e) between lecanemab (8.8%) and placebo (7.6%). the total incidence of aria (aria-e and/or aria-h) was 21.3% in the lecanemab group and 9.3% in the placebo group. overall, lecanemab’s aria incidence profile was within expectations.

clarity ad was a global confirmatory phase 3 placebo-controlled, double-blind, parallel-group, randomized study in 1,795 people with early ad. the treatment group was administered a dosage of 10 mg/kg bi-weekly of lecanemab, with participants allocated in a 1:1 ratio to receive either placebo or lecanemab. the baseline characteristics of both placebo and lecanemab groups are similar and well balanced. eligibility criteria allowed patients with a broad range of comorbidities/comedications: hypertension, diabetes, heart disease, obesity, renal disease and anti-coagulants, etc. eisai’s recruitment strategy for the clarity ad clinical trial ensured greater inclusion of ethnic and racial populations in the u.s., resulting in approximately 25% of the total u.s. enrollment including hispanic and african american persons living with early ad. due to the inclusive eligibility criteria and the successful recruitment of diverse ethnic and racial populations in the u.s., clarity ad’s population is generally comparable to the country’s medicare population.

“since eisai launched aricept in the u.s. and japan in the late 1990s and obtained its approval in over 100 countries, eisai has provided the drug to people living with dementia while building empathy for them and their families through disease education efforts and community involvement. the positive result of the lecanemab, an anti-aβ protofibril antibody, pivotal study after almost 25 years since aricept’s launch is an important milestone for eisai in fulfilling our mission to meet the expectations of the alzheimer’s disease community. alzheimer’s disease not only presents a great challenge for patients and their families, but it also negatively impacts society, including decreased productivity, increased social costs and disease-related anxiety. we believe that helping to alleviate these burdens will positively impact society as a whole,” said haruo naito, chief executive officer at eisai. “additionally, the lecanemab clarity ad study results prove the amyloid hypothesis, in which the abnormal accumulation of aβ in the brain is one of the main causes of alzheimer’s disease, when targeted with a protofibril-binding therapy. eisai believes these findings will create new horizons in the diagnosis and treatment of alzheimer’s disease as well as further activate innovation for new treatment options. the successful results of the clarity ad clinical trial would not be possible without the truly inspiring dedication of the study’s participants, their families and caregivers and the clinical investigators around the world. we thank all the people involved in the study for their invaluable contributions.”

“today’s announcement gives patients and their families hope that lecanemab, if approved, can potentially slow the progression of alzheimer’s disease, and provide a clinically meaningful impact on cognition and function,” said michel vounatsos, chief executive officer at biogen. “importantly, the study shows that removal of aggregated amyloid beta in the brain is associated with a slowing of disease in patients at the early stage of the disease. we want to thank the many patients who participated in this groundbreaking global study and want to acknowledge the clinical investigators who worked tirelessly to increase the enrollment of traditionally underrepresented populations. as pioneers in neuroscience, we believe defeating this disease will require multiple approaches and treatment options, and we look forward to continuing the discussion about the significance of these findings with the patient, scientific, and medical communities.”

in july 2022, the u.s. food and drug administration (fda) accepted eisai’s biologics license application (bla) for lecanemab under the accelerated approval pathway and granted priority review. the prescription drugs user fee act action date (pdufa) is set for january 6, 2023. the fda has agreed that the results of clarity ad can serve as the confirmatory study to verify the clinical benefit of lecanemab. in an effort to secure traditional fda approval for lecanemab as soon as possible, eisai submitted the bla through the fda’s accelerated approval pathway so that the agency could complete its review of all lecanemab data with the exception of the data from the confirmatory clarity ad study.

in march 2022, eisai began submitting application data, with the exception of clarity ad data, to japan’s pharmaceuticals and medical devices agency (pmda) under the prior assessment consultation system with the aim of obtaining early approval for lecanemab so that people living with early ad may have access to the therapy as soon as possible.

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) and nippon medac co., ltd. (headquarters: tokyo, ceo: hirohisa iriyama, “nippon medac”), a subsidiary of medac gesellschaft für klinische spezialpräparate mbh (headquarters: germany) announced today that they have obtained manufacturing and marketing approval from the japanese ministry of health, labour and welfare for the indication of the anti-rheumatic agent “metoject^® subcutaneous injection 7.5mg syringe 0.15ml, 10mg syringe 0.20ml, 12.5mg syringe 0.25ml and 15mg syringe 0.30ml” (methotrexate, “mtx”) for the treatment of rheumatoid arthritis. metoject will be the first self-administrable mtx subcutaneous injection formulation for rheumatoid arthritis in japan. based on the license agreement signed by eisai and medac gmbh in may 2019, nippon medac will hold the marketing authorization of metoject, while eisai will be responsible for product distribution of metoject in japan.

the approval is based on the results of a phase iii clinical trial (mc-mtx.17/ra) conducted in japan by nippon medac to compare the efficacy and safety of metoject with that of oral mtx, which consisted of a double-blind phase and an extension phase. in the double-blind phase of this trial, 102 rheumatoid arthritis patients who had not been treated with mtx received either 7.5 mg/week of metoject or 8 mg/week of oral mtx for 12 weeks in repeated doses. the primary endpoint of acr20 response* at 12 weeks was 59.6% in the metoject group versus 51.0% in the oral mtx group, indicating comparable efficacy. the adverse drug reaction incidence rates in this trial were 25.0% in the metoject group and 34.0% in the oral mtx group. in the double-blind phase, the most common adverse drug reactions (incidence 5% and higher) were stomatitis (5.8%) in the metoject group, and nausea (12.0%) and stomatitis (6.0%) in the oral mtx group.

it is reported that there are approximately 700,000 – 800,000 rheumatoid arthritis patients in japan¹. mtx is used as the first-line option for the treatment of rheumatic arthritis, but only the oral formulation is available in japan. eisai and nippon medac will provide a self-administrable subcutaneous injection as a new treatment option for rheumatoid arthritis patients in japan as soon as possible, and will make further contributions to address the diversified needs of, and increase the benefits provided to, rheumatoid arthritis patients.

* acr20 is a criterion developed by the american college of rheumatology that measures improvement in clinical symptoms of rheumatoid arthritis. it expresses the percentage of patients who demonstrated a 20% or greater improvement in tender and swollen joint counts and at least three of the following five disease activity variables: patient assessment of pain; patient assessment of global disease activity; physician assessment of global disease activity; patient assessment of physical function; and chronic response protein or erythrocyte sedimentation rate concentrations.

media inquiries

eisai co., ltd.

public relations department

tel： 81-(0)3-3817-5120

nippon medac co., ltd.

ueno

tel： 81-(0)3-6661-6270

findings to be featured in a late-breaking proffered paper session at european society for medical oncology (esmo) congress 2022

tokyo and rahway, n.j., september 12, 2022 – eisai (headquarters: tokyo, ceo: haruo naito, “eisai”) and merck & co., inc., rahway, nj, usa (known as msd outside of the united states and canada) today announced the first presentation of results from the final analysis of the phase 3 leap-002 trial investigating lenvima^®, the orally available multiple receptor tyrosine kinase inhibitor discovered by eisai, plus keytruda^®, the anti-pd-1 therapy from merck & co., inc., rahway, nj, usa versus lenvima monotherapy, as a first-line treatment for patients with unresectable hepatocellular carcinoma (uhcc). results are being presented during a proffered paper session at the european society for medical oncology (esmo) congress 2022, being held in paris, france and virtually from sept. 9-13 (abstract #lba34).

in the final analysis of the trial, there was a trend toward improvement for one of the study’s dual primary endpoints, overall survival (os), for patients treated with lenvima plus keytruda versus lenvima monotherapy; however, the results did not meet statistical significance per the pre-specified statistical plan (hr=0.84 [95% ci: 0.71-1.00]; p=0.0227). the median os was 21.2 months (95% ci: 19.0-23.6) for lenvima plus keytruda and 19.0 months (95% ci: 17.2-21.7) for lenvima monotherapy. additionally, treatment with lenvima plus keytruda resulted in a trend toward improvement in the trial’s other dual primary endpoint of progression-free survival (pfs) versus lenvima monotherapy; however, the results did not meet the pre-specified threshold at the first interim analysis for statistical significance (hr=0.87 [95% ci: 0.73-1.02]; p=0.0466).

“the leap-002 trial reflects our research strategy to build on evolving standards of care to further improve outcomes for more people with unresectable hepatocellular carcinoma,” said dr. gregory lubiniecki, vice president, global clinical development, merck & co., inc., rahway, nj, usa research laboratories. “the median overall survival of 21.2 months seen with keytruda plus lenvima provides critical insights for further research into the potential role of this combination.”

“while the outcome is not what we had hoped, it is important for us to see that patients in the trial treated with lenvima monotherapy had a median overall survival of 19.0 months,” said corina dutcus, m.d., senior vice president, clinical research, oncology at eisai inc. “findings from the leap-002 trial will not only help advance our understanding and application of lenvima plus keytruda across our clinical development program but will also provide physicians with additional information on lenvima monotherapy’s use in unresectable hepatocellular carcinoma, where it is currently approved as a treatment option in multiple regions around the world, including the u.s., the european union (eu), japan and china.”

lenvima monotherapy is approved for the first-line treatment of patients with uhcc in the u.s., the eu and china and for patients with uhcc in japan. the approval of lenvima was based on results of the phase 3 reflect trial, which evaluated the efficacy and safety of lenvima versus sorafenib for the first-line treatment of patients with uhcc.

lenvima (marketed as kisplyx^® for renal cell carcinoma [rcc] in the eu) plus keytruda is approved in the u.s., the eu and japan for the treatment of certain types of advanced endometrial carcinoma and advanced rcc. eisai and merck & co., inc., rahway, nj, usa are studying the lenvima plus keytruda combination through the leap (lenvatinib and pembrolizumab) clinical program in multiple tumor types, including but not limited to endometrial carcinoma, hcc, melanoma, non-small cell lung cancer, rcc, head and neck cancer, colorectal cancer, gastric cancer and esophageal cancer, across more than 15 clinical trials.

leap-002 study design and final analysis results (abstract #lba34)

leap-002 is a multicenter, randomized, double-blinded, active-controlled phase 3 trial (clinicaltrials.gov, ) evaluating lenvima plus keytruda versus lenvima monotherapy for the first-line treatment of adult patients with uhcc. patients were randomized 1:1 to receive lenvima (12 mg orally once daily [for patients with screening body weight of at least 60 kg] or 8 mg orally once daily [for patients with screening body weight less than 60 kg]) plus keytruda (200 mg intravenously [iv] on day 1 of each three-week cycle); or lenvima (12 mg orally once daily [for patients with screening body weight of at least 60 kg] or 8 mg orally once daily [for patients with screening body weight less than 60 kg]) plus saline placebo (iv administered on day 1 of each three-week cycle). lenvima was administered until progressive disease or unacceptable toxicity. keytruda/placebo was administered for up to 35 cycles (approximately two years).

the dual primary endpoints were pfs, as assessed by blinded independent central review (bicr) per response evaluation criteria in solid tumors version 1.1 (recist v1.1; recist v1.1 has been modified for this study to follow a maximum of 10 target lesions in total and a maximum of five target lesions per organ), and os. objective response rate (orr), as assessed by bicr per recist v1.1, was a key secondary endpoint. the trial was designed with two interim analyses and a final analysis for os. pre-specified efficacy boundaries were one-sided p=0.002 for pfs at interim analysis 1 and p=0.0185 for os at the final analysis.

as of the data cut-off for the final analysis (june 21, 2022), a total of 794 patients were enrolled and treated, with a median follow-up of 32.1 months (range, 25.8-41.1). a total of 534 os events had occurred, with 36 patients (9.1%) in the combination arm and 24 patients (6.1%) in the lenvima monotherapy arm remaining on study treatment.

the median os was 21.2 months (95% ci: 19.0-23.6) for lenvima plus keytruda versus 19.0 months (95% ci: 17.2-21.7) for lenvima monotherapy at the final analysis. the median pfs was 8.2 months (95% ci, 6.4-8.4) for lenvima plus keytruda versus 8.0 months (95% ci: 6.3-8.2) for lenvima monotherapy at the first interim analysis and 8.2 months (95% ci: 6.3-8.3) versus 8.1 months (95% ci: 6.3-8.3), respectively, at the final analysis. the orr was 26.1% (95% ci: 21.8-30.7) for lenvima plus keytruda versus 17.5% (95% ci: 13.9-21.6) for lenvima monotherapy at the final analysis. median duration of response was 16.6 months (range, 2.0 to 33.6 ) in the keytruda plus lenvima arm versus 10.4 months (range, 1.9 to 35.1 ) in the lenvima monotherapy arm at the final analysis.

the safety profile of lenvima plus keytruda was consistent with previously reported data on the combination. grade 3-4 treatment-related adverse events (traes) occurred in 61.5% of patients treated with lenvima plus keytruda versus 56.7% of patients treated with lenvima monotherapy. grade 5 traes occurred in 1.0% of patients treated with lenvima plus keytruda versus 0.8% of patients treated with lenvima monotherapy. in patients treated with lenvima plus keytruda, the five most common traes of any grade were hypertension (43.3%), diarrhea (40.3%), hypothyroidism (40.0%), palmar-plantar erythrodysesthesia (ppe) syndrome (33.2%) and proteinuria (30.6%). in patients treated with lenvima monotherapy, the five most common traes of any grade were hypertension (46.8%), hypothyroidism (35.7%), proteinuria (34.9%), diarrhea (33.9%) and ppe syndrome (30.6%). post-study systematic anti-cancer treatments were given for 44.1% of patients receiving lenvima plus keytruda versus 52.1% of those receiving lenvima monotherapy.

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merck & co., inc., kenilworth, n.j., u.s.a.

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to strengthen its research and development function for injectable drug formulations

findings to be featured in a late-breaking proffered paper session at european society for medical oncology (esmo) congress 2022

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