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eisai co.,ltd.(headquarters: tokyo, ceo: haruo naito, “eisai”) announced its latest data of nonclinical research which examined the effect to the synaptic function in the brain by spinal densities^*1 in regard to oral bace (beta-site amyloid precursor protein cleaving enzyme) inhibitor elenbecestat^*2 were presented at the alzheimer’s association international conference (aaic) held in los angeles, california, united states, from july 14 to 18, 2019 (poster presentation no.: p2-064).

bace is a key enzyme in the production of aβ peptides, which inhibits β site of amyloid precursor protein (app). bace inhibitor may decrease the formation of toxic aβ peptide aggregates in the brain, thereby thought to exert disease modifying effects and may have potential to slow the disease progression. on the other hand, in addition to app, the other substrates with physiological role in synapse formation and function are known as a substance (substrate) changed by bace. at this time, the effect to aβ level in csf and synaptic damage were examined after 4 weeks of administration of bace inhibitors using novel preclinical model mouse. for the examination compounds, elenbecestat (in-house discovery), verubecestat, and lanabecestat were used. in addition, the effect to the synapse formation and function were evaluated by setting the numerous spinal densities on dendrite of brain cortex (number of spines per 10 μm of dendrites) and mitochondrial function (mitochondrial oxygen efficiency) of hippocampal synaptosomes (isolated presynaptic terminal) as an index. it is believed that decreases in spinal densities and mitochondrial function damage the synaptic function and deteriorate the cognitive function.

the dose of each base inhibitor was adjusted so as to be equivalent to the dose for clinical study in accordance with exploratory data of lowering effect of aβ in mouse csf.

as a result, elenbecestat did not show significant effects on spinal density and mitochondrial function at dose of 3, 10mg/kg with significant decline of aβ level in csf (p<0.001).

as for the verubecestat, significant decline of spinal density was shown at the dose of 10, 30mg/kg (p<0.05) with significant decline of aβ level in csf (p<0.001).

also, as for lanabecestat, significant decline of spinal density was shown at the dose of 30, 100mg/kg (p<0.05) with the significant decline of aβ level in csf (p<0.001), as well as the significant decline of mitochondrial function was shown at the dose of 100mg/kg (p<0.05).

these results suggest that elenbecestat does not affect the synaptic function in the brain with an effective dose to decline the aβ level in csf.

eisai aims to realize the prevention and cure of dementia through a multi-dimensional and holistic approach with a foundation of over 35 years of experience of drug discovery activities in the area of alzheimer’s disease and dementia. eisai strives to create innovative medicines as soon as possible to further contribute to addressing the unmet medical needs of, as well as increasing the benefits provided to, patients and their families.

^*1 there are more than 100 billion nerve cells (neurons) in the brain, the information is transmitted by forming each bond, called a synapse. this synapse is formed between the axon terminal (presynaptic neuron) sending information and the neuron dendrite (postsynaptic neuron) receiving information. many supraspinal structures on the neuron dendrite which forms synapse is called spine.

^*2 elenbecestat, is being jointly developed by eisai and biogen inc. (headquarters: cambridge, massachusetts, united states, “biogen”).

media inquiries:
public relations department,
eisai co., ltd.
81-(0)3-3817-5120

[notes to editors]
1. about elenbecestat (generic name, development code: e2609)
discovered by eisai, elenbecestat is an investigational next-generation oral candidate for the treatment of alzheimer’s disease (ad) that inhibits bace (beta amyloid cleaving enzyme). by inhibiting bace, a key enzyme in the production of aβ peptides, elenbecestat reduces aβ production, and by reducing amyloid plaque formations in the brain, exerts disease modifying effects of potentially slowing the progression of ad. currently, two global phase iii clinical studies (mission ad1/2) of elenbecestat in early ad including mild cognitive impairment (mci) due to ad or the mild ad are underway. in addition, the u.s. food and drug administration (fda) has granted fast track designation for the development of elenbecestat, a process allowing priority reviews by the fda for drugs deemed as having potential to treat serious conditions and tackle key unmet medical needs.

2. about joint development agreement between eisai and biogen for alzheimer’s disease
eisai and biogen are collaborating on the joint development and commercialization of alzheimer’s disease treatments. eisai serves as the lead in the co-development of elenbecestat, a bace inhibitor, and ban2401, an anti-amyloid beta (aβ) protofibril antibody, and the companies plan to pursue marketing authorizations for the two compounds worldwide. if approved, the companies will also co-promote the products in major markets, such as the united states, the european union and japan. as to ban2401 and elenbecestat, both companies will equally split overall costs, including research and development expenses. eisai will book all sales for elenbecestat and ban2401 following marketing approval and launch, and profits will be equally shared between the companies.

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that eisai received new drug approval for eisai’s in-house developed anticancer agent eribulin mesylate (halaven®) for use in the treatment of patients with locally advanced or metastatic breast cancer, previously treated with at least two prior chemotherapy regimens, including an anthracycline and a taxane, from the china national medical products administration (nmpa).

this approval is based on the results of study 304,¹ which was a multicenter, open-label, randomized, parallel group phase iii clinical study, to evaluate the efficacy and safety of eribulin and vinorelbine in 530 women with locally recurrent or metastatic breast cancer, previously treated with chemotherapy regimens, including an anthracycline and a taxane. eribulin demonstrated a statistically significant extension in the study’s primary endpoint of progression-free survival (pfs) over the comparator treatment vinorelbine according to independent imaging review (hazard ratio: 0.80; 95% confidence interval: 0.65-0.98; p = 0.036).
the five most common adverse events observed in the eribulin arm of this study were white blood cell count decreased, neutrophil count decreased, increased aspartate aminotransferase, increased alanine aminotransferase, and anemia, which is consistent with the known side-effect profile of eribulin.

the number of women diagnosed with breast cancer in china has increased in recent years,² and breast cancer is now the most frequently diagnosed cancer in chinese women.³

eribulin is a halichondrin class microtubule dynamics inhibitor with a distinct binding profile. in addition to its mechanism of action of inhibiting the growth of microtubule dynamics, non-clinical studies showed eribulin’s unique actions on the tumor microenvironment such as an increase in vascular perfusion and permeability in tumor cores,⁴ promotion of the epithelial state, decrease in the capacity of breast cancer cells to migrate,⁵ etc. for use in the treatment of breast cancer, eribulin is currently approved in over 65 countries worldwide, including the united states, japan and countries in europe and asia.

eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. lenvima® has been available as a treatment of patients with unresectable hepatocellular carcinoma who have not received prior systematic therapy in china since november 2018. with this approval of eribulin, eisai seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers in china.

media inquiries:
public relations department,
eisai co., ltd.
81-(0)3-3817-5120

[notes to editors]
1. about eribulin mesylate
eribulin is in the halicondrin class of microtubule dynamics inhibitors with a novel mechanism of action. structurally, eribulin is a simplified and synthetically produced version of halichondrin b, a natural product isolated from the marine sponge halichondria okadai. eribulin is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division. in addition, non-clinical studies showed eribulin’s unique actions in the tumor microenvironment such as an increase in vascular perfusion and permeability in tumor cores,⁴ promotion of the epithelial state, decrease in capacity of breast cancer cells to migrate,⁵ and etc.
eribulin was first approved as a treatment in the united states in november 2010 for patients with metastatic breast cancer. eribulin is currently approved for use in the treatment of breast cancer in over 65 countries worldwide, including japan and countries in europe, the americas and asia. furthermore, eribulin was first approved as a treatment for soft tissue sarcoma in the united states in january 2016, and is approved in over 60 countries including japan and in europe and asia. furthermore, eribulin has been designated as an orphan drug for soft tissue sarcoma in the united states and japan.

specifically, eribulin is approved for the following indications.
in the united states for the treatment of patients with:

• metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.

• unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen.

in japan for the treatment of patients with:

• inoperable or recurrent breast cancer

• soft tissue sarcoma

in europe for the treatment of adult patients with:

• locally advanced or metastatic breast cancer who have received a prior anthracycline-containing regimen for advanced disease. prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments.

• unresectable liposarcomas who have received prior anthracycline containing therapy (unless unsuitable) for advanced or metastatic disease.

2. about study 304¹
conducted in china, study 304 was a multicenter, open-label, randomized, parallel group phase iii clinical study to evaluate the efficacy and safety of eribulin and vinorelbine in 530 female patients with locally recurrent or metastatic breast cancer, previously treated with at least two and a maximum of five prior chemotherapy regimens, including an anthracycline and a taxane. patients received either eribulin (1.4mg/m² administered intravenously on day 1 and day 8 to 264 patients) or vinorelbine (25 mg/m² administered intravenously on day 1, day 8 and day15 to 266 patients) every 21 days. the study’s primary endpoint was progression-free survival (pfs).

¹yuan p et al., eribulin mesilate versus vinorelbine in women with locally recurrent or metastatic breast cancer: a randomized clinical trial eur j cancer, 2019; 112, 57-65
²lei f et al., breast cancer in china. the lancet oncology, 2014; 15(7), e279–e289
³ ferlay j, et al., (2018). global cancer observatory: cancer today. lyon, france: international agency for research on cancer. , as of july 17, 2019
⁴funahashi y et al., eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models. cancer sci., 2014; 105, 1334-1342
⁵yoshida t et al., eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (emt) to mesenchymal-epithelial transition (met) states. br j cancer, 2014; 110, 1497-1505

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that it has been included in the ftse4good index series for the 18th consecutive year since its initial inclusion in 2002. the ftse4good index series is a global index series for socially responsible investment.

the ftse4good index series is designed to help investors integrate the global standard factors of environmental, social and governance (esg) into their investment decisions. eisai received particularly high scores in “customer responsibility”, “labor standards”, “corporate governance”, “anti-corruption”, and “climate change”, among others. as of july 2019, a total of 1,034 companies from around the world have been selected for the ftse4good developed index, including 175 companies from japan.

along with being listed in the ftse4good index series, eisai is also listed in the msci japan empowering women index (win), the ftse blossom japan index, the msci japan esg select leaders index, and s&p/jpx carbon efficient index, which are the four esg investment indices for japanese stocks adopted by the government pension investment fund (gpif).

eisai’s corporate philosophy is to give first thought to patients and their families, and increase the benefits that health care provides as well as address diverse healthcare needs worldwide. by strengthening its esg initiatives and increasing non-financial value, eisai is striving to sustainably enhance corporate value based on this corporate philosophy.

media inquiries:
public relations department,
eisai co., ltd.
81-(0)3-3817-5120

a focused drug discovery approach that integrates human genetics / data science / precision chemistry

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that the eisai center for genetics guided dementia discovery (g2d2), a new exploratory research facility in cambridge, massachusetts, u.s., held its opening ceremony and has begun full-scale research activities.

(standing from left to right) ryan fattman, u.s. senator for massachusetts; mike belleville, patient living with dementia; haruo naito, eisai ceo; yoshito kishi, morris loeb professor of chemistry, harvard university; yasushi nakamura, acting consul general at consulate general of japan in boston; mark fuller, undersecretary for business growth, executive office of economic development.

g2d2 integrates eisai’s strengths cultivated from human genetics, data sciences and precision chemistry for the novel drug discovery approach, and this approach will focus on the immunodementia to expand eisai’s dementia pipeline beyond amyloid-beta (aβ) and tau. specifically, g2d2 will leverage human genetics and human biology to attempt to discover potential innovative medicines for dementia, which target the brain’s immune system.

g2d2 is located in cambridge, massachusetts, one of the world’s leading biotechnology clusters where academic institutions and private research organizations are concentrated, and will collaborate with the world-class science. taking advantage of the benefits of its location, the eisai incubator for neurodiscovery (e-ind) will provide space to cambridge-based start-up/spin-out companies conducting high-risk but potentially transformative research that can impact the discovery of breakthrough neuroscience therapeutics. g2d2 also plans to contribute to the development of next-generation scientific leaders in the boston and cambridge areas through internships, training programs and postdoctoral fellowships in genetics and drug discovery science.

with the full-scale operation of g2d2, eisai is striving to discover innovative dementia treatments using a multi-dimensional, comprehensive approaches to fulfill unmet needs and increase the benefits for patients and their families.

media inquiries:
public relations department,
eisai co., ltd.
81-(0)3-3817-5120

[notes to editors]
1. about immunodementia
drug discovery targets supported by human genetics have been demonstrated to have a higher probability of success than drug targets that are not. large-scale genetic and other studies of alzheimer’s disease have highlighted neuro-immune regulating factors of a particular cell-type, microglia, as likely being causal in the onset of dementia. integrating cutting-edge strengths in human genetics, data sciences and precision chemistry, g2d2 will focus on a new research theme of immunodementia, a novel genetically validated target modulating immune mechanism that treats dementia, to extend eisai’s discovery pipeline beyond targeting amyloid and tau. under the medium-term business plan eway2025 currently in progress, immunodementia is a ricchi (an area where real patient needs are unmet and eisai can become a frontrunner) in neurology.

2. eisai’s initiatives for dementia research
eisai possesses experience cultivated through over 35 years of drug creation activities in the dementia area, including the development of aricept^® as a standard treatment for alzheimer’s disease, as well as a rich development pipeline. with tsukuba research laboratories as its hub, the company is working on global exploratory development of research for dementia treatments using a multi-dimensional, comprehensive approaches by following global research sites:

・tsukuba research laboratories (japan): a hub for drug discovery research with abundant experiences in small molecules for the central nervous system;
・g2d2 (u.s.): research on immunodementia with the strengths in human genetics, data sciences and precision chemistry;
・kan research institute (kobe, japan): research on glial cell based on cellular biology;
・european knowledge centre (hatfield, u.k.): open innovation drug discovery through cooperation with u.k. academia;
and
・eisai-keio innovation lab for dementia (japan): brain defense mechanism research based on reverse translation.

3. photographs of inside and outside of g2d2

(outside) (eisai incubator for neurodiscovery)

(equipment of data science) (space of precision chemistry)

july 3, 2019 – eisai china inc. announced that it would again donate 350,000 yuan to china population welfare foundation for the project “public welfare stars invite you to help the elderly with cognitive impairment go home”, which was jointly organized by china population welfare foundation and tencent news.

it was reported that this charitable activity will be carried out with “stars appealing and netizens forwarding the appeals”. each forwarding by a participant will bring one “helping hand”, which is equivalent to one yuan donated to the charitable fund, and one yellow bracelet will be donated for every 326 yuan, or 326 times of forwarding. the charitable money will be donated by benevolent enterprises (scan the two-dimensional code below for details of the activity). this activity aims to call public attention to patients with cognitive impairment.

the related funds donated by eisai china inc., one of the benevolent enterprises, will be used to purchase 1,000 positioning yellow bracelets. patients with cognitive impairment and their families can get the yellow bracelets for free in memory clinics of relevant hospitals. the positioning yellow bracelet has the functions of real-time positioning, movement track checking, safety fence, emergency call and so on. families of the elderly can track and positioning the location of the elderly through mobile app, which help change passive search into active care.

cognitive impairment is a progressive declining brain disease, which is often mistaken for normal aging. in addition to the misunderstandings, there is still serious discrimination against the elderly with cognitive impairment in our society. what’s more, such patients have a strong sense of shame, resulting in a low rate of medical treatment. the disease is still incurable up to now, which brings heavy burdens in finance, care-giving and psychology to families of such patients. china sees large population with cognitive impairment and high incidence of the disease with tens of millions of such patients becoming a huge challenge in the aging society.

since entering china market in the 1990s, we have always been adhering to our company philosophy of hhc (human health care), giving our first thoughts to patients and their families, and to increasing the benefits health care provides. we always commit to promoting the progress and development of neuroscience, one of the key treatment fields we focus on.

in 2019, we will continue to cooperate with the china population welfare foundation to promote a total of nearly 200 online and offline activities regarding yellow bracelets, which is expected to benefit more than 10,000 people, as well as large-scale science popularizations and free clinics. meanwhile, we will collect caregiver stories jointly with china association for alzheimer’s disease and carry out online disease education and more activities in cooperation with jd.com. we are willing to work with all sectors of the society to improve the life quality of patients, promote the development of disease-related industries, enhance social understanding and prevention of the disease and actively help improve public policies to address the challenges brought by an ageing society.

on june 24, 2019, eisai china inc. was invited to participate in the “health to countryside” activity, which was organized by the education, science, health and sports committee of cppc in qinghai province, and donated drugs worth of about rmb 530,000 yuan to the qinghai red cross society, which will be used in the “health to countryside” activity in qinghai province. eisai china has always been adhering to its hhc (human health care) corporate philosophy, actively participating in charitable activities and bearing its social responsibilities. from 2014 to 2019, we have donated medicines worth of about rmb 3 million yuan through the “health to countryside” campaign.

the honorary credential granted eisai china inc.

the “health to countryside” is hosted by the education, science, health and sports committee of cppc and undertook by the chinese pharmaceutical association to provide health assistance to huangzhong county of xining city, guide county of the hainan tibetan autonomous prefecture, gangcha county of haibei tibetan autonomous prefecture and xihai town of haibei prefecture of qinghai province etc. it is an important activity organized annually by the education, science, health and sports committee of cppc and a traditional activity to implement the cppcc constitution, providing not only basic medical services, medicines, concepts, technologies and management, but also charity clinics and lectures etc., which close the distance between the committee members, experts, doctors, enterprises and the masses.

the core of the “hhc” concept of eisai china is to give our first thoughts to patients and their families, actively communicate with patients and meet the needs of both patients and their families. eisai china advocates that every employee should spend 1% of their working time with patients every year to practice hhc. only by understanding the patients’ feelings and pains, we could provide better services, introduce products that the patients really need and win the trust of both the patients and their families on the products and services of eisai china. eisai china attaches great importance to corporate social responsibility and will continue to devote its corporate love to the “health to countryside” under the leadership of ms. feng yanhui, the president of eisai china, and contribute to the medical and health career in the poverty-stricken areas.

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that a joint research group including scientists from eisai and professor yoshito kishi’s group of harvard university has achieved a total synthesis and obtained results of nonclinical studies of the novel compound, e7130, derived from total synthesis of halichondrin. these results have been published in scientific reports, a scientific journal of nature.¹ currently a phase i study to investigate e7130 in solid tumor is underway in japan.

halichondrins, which was isolated from the marine sponge halichondria okadai in 1986, was known for their outstanding antitumor activity in mice, however the supply from natural sources were limited. furthermore, the very complicated chemical structure has prevented drug discovery and development based on intact halichondrins. the joint research group strictly controlled 31 asymmetric carbons and achieved a total synthesis of e7130, on a >10 g scale with >99.8% purity under gmp (good manufacturing practice) conditions.
the joint research team also demonstrated that e7130 is not only a novel microtubule dynamics inhibitor but can also increase intratumoral cd31-positive endothelial cells (vascular remodeling activity) and reduce alpha-sma (smooth muscle actin)-positive cancer-associated fibroblasts (anti-caf effect), which are important constituents of the tumor microenvironment and may be involved in the malignant transformation of cancers in nonclinical in vivo studies.

according to these unique effects, e7130 augments the effect of antitumor treatments in nonclinical studies. overall, our work demonstrates that a total synthesis can address the issue of limited material supply in drug discovery and development even for complex natural products.

“in 1992, it was unthinkable to synthesize a gram-quantity of a halichondrin,” said yoshito kishi, morris loeb professor of chemistry, emeritus, in the department of chemistry and chemical biology at harvard university, said “but three years ago we proposed it to eisai. organic synthesis has advanced to that level, even with molecular complexity that was untouchable several years ago. we are very delighted to see our basic chemistry discoveries have now made it possible to synthesize this compound at large scale.”

eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. we will maximize the potential of halichondrins by adding e7130 project to two investigational projects of eisai’s eribulin platform; morab-202 (antibody-drug conjugate with eribulin as the payload) and liposomal formulation of eribulin, as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

* harvard has exclusively licensed the intellectual property associated with this research project to eisai for the commercial development of therapeutics.

media inquiries:
public relations department,
eisai co., ltd.
81-(0)3-3817-5120

[notes to editors]
about e7130
e7130 is a next-generation agent improving tumor microenvironment, which has been developed by a joint research with eisai and harvard university. e7130 is derived from total synthesis of halichondrin, a natural product isolated from the marine sponge halichondria okadai. e7130 is believed to improve tumor microenvironment by unique action for potential effect on immune activation by releasing hypoxia and suppressing interaction between cancer cells and stroma. a phase i study to investigate e7130 in solid tumor is currently underway in japan.

^1. kawano s et al., “a landmark in drug discovery based on complex natural product synthesis” scientific reports 2019.

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that the latest data on its antiepileptic drug (aed) perampanel (product name: fycompa^®) will be presented at the 33^rd international epilepsy congress (iec) to be held from june 22 to 26, 2019 in bangkok, thailand.

as major presentations, 2 oral presentations will be given including on the final analysis of a phase iii clinical study (study 311) on adjunctive perampanel in pediatric patients aged 4 to less than 12 years old with epilepsy. also, a total of 12 poster presentations will be given, including on the primary analysis from a phase iii clinical study (freedom / study 342), which was conducted in japan and south korea, on the efficacy and safety of perampanel monotherapy in untreated epilepsy patients with partial-onset seizures (with or without secondary generalized seizures).

perampanel is a first-in-class aed and a once-daily tablet discovered at eisai’s tsukuba research laboratories. in the united states and europe, an oral suspension formulation has been approved and is being marketed. the agent is a highly selective, noncompetitive ampa receptor antagonist that reduces neuronal hyperexcitation by targeting glutamate activity at ampa receptors on postsynaptic membranes. perampanel is currently approved in countries around the world as an adjunctive therapy for the treatment of partial-onset seizures (with or without secondary generalized seizures) and primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older. furthermore, in the united states, perampanel is approved for monotherapy and adjunctive use in the treatment of partial-onset seizures (with or without secondary generalized seizures) in patients with epilepsy 4 years of age and older.

eisai considers neurology including epilepsy, a therapeutic area of focus, and strives to deliver perampanel throughout the world in pursuit of our mission to provide “seizure freedom” to a greater number of patients living with epilepsy. eisai seeks to address the diverse needs of, as well as increasing the benefits provided to, patients with epilepsy and their families.

oral presentations

presentation number and scheduled presentation date (local time)	abstract title
platform session: treatment oral presentation: monday, june 24th 15:30-15:45	safety and efficacy of adjunctive perampanel in paediatric patients (aged 4 to <12 years) with partial-onset seizures (pos) or primary generalised tonic-clonic seizures (pgtcs): final results from the 311 core study
platform session: treatment oral presentation: monday, june 24th 15:45-16:00	effect of concomitant enzyme-inducing anti-seizure drugs (eiasds) on the safety and efficacy of adjunctive perampanel in patients aged 4 to <12 years with partial-onset seizures (pos): final results from the 311 core study

presentation number and scheduled presentation date (local time)

abstract title

platform session: treatment

oral presentation:

monday, june 24th 15:30-15:45

safety and efficacy of adjunctive perampanel in paediatric patients (aged 4 to <12 years) with partial-onset seizures (pos) or primary generalised tonic-clonic seizures (pgtcs): final results from the 311 core study

platform session: treatment

oral presentation:

monday, june 24th 15:45-16:00

effect of concomitant enzyme-inducing anti-seizure drugs (eiasds) on the safety and efficacy of adjunctive perampanel in patients aged 4 to <12 years with partial-onset seizures (pos): final results from the 311 core study

poster presentations

presentation number and scheduled presentation date (local time)	abstract title
poster # p125 poster session: drug therapy 1 poster presentation: sunday, june 23rd 10:00-17:00	first-line perampanel added to monotherapy in patients with partial-onset seizures, with or without secondary generalised seizures: a multicentre, open-label, prospective cohort study
poster # p215 poster session: paediatric epileptology 1 poster presentation: sunday, june 23rd 10:00-17:00	adjunctive perampanel in pediatric patients with epilepsy: population pharmacokinetic (pk) and exposure-response analyses
poster # p317 poster session: drug therapy 2 poster presentation: monday, june 24th 10:00-17:00	perampanel does not worsen myoclonic and absence seizures
poster # p328 poster session: drug therapy 2 poster presentation: monday, june 24th 10:00-17:00	perampanel in real-world clinical care of patients with epilepsy: retrospective phase iv study 506 (prove study)
poster # p329 poster session: drug therapy 2 poster presentation: monday, june 24th 10:00-17:00	study 506 (prove study) – a retrospective, phase iv study of perampanel in real-world clinical care of patients with epilepsy: adolescent subgroup (aged 12 to <18 years)
poster # p331 poster session: drug therapy 2 poster presentation: monday, june 24th 10:00-17:00	efficacy and safety of adjunctive perampanel in chinese patients with partial-onset seizures or primary generalised tonic-clonic seizures: post hoc analysis of phase iii double-blind and open-label extension studies
poster # p410 poster session: paediatric epileptology 2 poster presentation: monday, june 24th 10:00-17:00	safety and efficacy of adjunctive perampanel in younger (aged 4 to < 7 years) and older (7 to < 12 years) paediatric patients with partial-onset seizures (pos) or primary generalised tonic-clonic seizures (pgtcs): final results from the 311 core study
poster # p413 poster session: paediatric epileptology 2 poster presentation: monday, june 24th 10:00-17:00	study 506 (prove study) – a retrospective, phase iv study of perampanel in real-world clinical care of patients with epilepsy: paediatric subgroup (aged <12 years)
poster # p424 poster session: paediatric epileptology 2 poster presentation: monday, june 24th 10:00-17:00	effect of adjunctive perampanel on clinical global impression (cgi) in paediatric patients (aged 4 to <12 years) with partial-onset seizures (pos) or primary generalised tonic-clonic seizures (pgtcs) in study 311
poster # p425 poster session: paediatric epileptology 2 poster presentation: monday, june 24th 10:00-17:00	safety and efficacy of adjunctive perampanel in japanese paediatric patients (aged 4 to < 12 years) with partial-onset seizures (pos) with or without secondarily generalised seizures (sgs): final results from the 311 core study
poster # p315 poster session: drug therapy 3 poster presentation: tuesday, june 25th 10:00-17:00	efficacy and safety of perampanel monotherapy in previously untreated patients with partial-onset seizures (pos): primary analysis of study 342 (freedom study)
poster # p520 poster session: drug therapy 3 poster presentation: tuesday, june 25th 10:00-17:00	efficacy and safety of adjunctive perampanel in indian patients with partial-onset seizures (pos) or primary generalised tonic-clonic seizures (pgtcs): post hoc analysis of phase ii and iii double-blind and open-label extension (olex) studies

media inquiries:
public relations department,
eisai co., ltd.
81-(0)3-3817-5120

[notes to editors]
1. about perampanel (generic name, product name: fycompa)
perampanel is a first-in-class aed discovered and developed by eisai. with epileptic seizures being mediated by the neurotransmitter glutamate, the agent is a highly selective, noncompetitive ampa receptor antagonist that reduces neuronal hyperexcitation by targeting glutamate activity at ampa receptors on postsynaptic membranes. perampanel is available in tablet form to be taken once daily orally at bedtime. in addition, an oral suspension formulation has been approved and is being marketed in the united states and europe.

perampanel is currently approved in more than 55 countries, including the united states, japan, in europe and in asia as adjunctive treatment for partial-onset seizures (with or without secondarily generalized seizures) in patients with epilepsy 12 years of age and older. an application seeking approval for use in the adjunctive treatment of partial-onset seizures is under review in china, which has been designated for priority review. in addition, perampanel has been approved in more than 50 countries, including the united states, japan, in europe and in asia for treatment as an adjunctive therapy for tonic-clonic seizures in patients with generalized epilepsy 12 years of age and older. in the united states, perampanel is approved for monotherapy and adjunctive use in the treatment of partial-onset seizures (with or without secondarily generalized seizures) in patients with epilepsy 4 years of age and older. in japan, a supplementary new drug application has been filed seeking approval of perampanel for use as monotherapy for partial-onset seizures, treatment for partial-onset seizures in pediatric patients aged 4 years and older, as well as a fine granule formulation. in europe, an application has been submitted seeking the additional approval of perampanel for adjunctive use in the treatment of partial-onset seizures (with or without secondarily generalized seizures) or primarily generalized tonic-clonic seizures in pediatric patients with epilepsy.

furthermore, eisai is conducting a global phase iii clinical study (study 338) for the agent in patients with epileptic seizures associated with lennox-gastaut syndrome.

eisai co.,ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) today announced that latest information on lemborexant, an investigational sleep-wake regulation agent being studied for the treatment of multiple sleep-wake disorders, including insomnia and irregular sleep-wake rhythm disorder (iswrd) will be presented at the 33rd annual meeting of the associated professional sleep societies (sleep 2019), from june 8 to 12 in san antonio, texas, the united states.

eight posters including the integrated analysis of lemborexant’s effects on daily function and disease severity as well as sleep onset and sleep maintenance for the combined 1,955 patient population of two pivotal clinical phase iii studies, sunrise 1 (study 304) and sunrise 2 (study 303) in insomnia disorders, and an evaluation of results on respiratory function after administration of lemborexant in elderly and mild obstructive sleep apnea, and the latest pre-clinical data on iswrd will be presented.

lemborexant acts on the orexin neurotransmitter system and is believed to regulate sleep and wake by controlling arousal without affecting awakening by external stimuli, and is being developed for the treatment of multiple sleep-wake disorders including insomnia disorder. in december 2018 and march 2019, new drug applications seeking approval of lemborexant for use in the treatment of insomnia disorder were submitted in the united states and japan, respectively. for the ongoing clinical studies, please visit clinicaltrials.gov.

through the development of lemborexant, eisai is aiming to bring to patients suffering from sleep-wake disorders a new treatment option to improve their ability to fall and stay asleep and wake without impairing the next morning, and is striving to further contribute to satisfying unmet medical needs and improve the benefits to patients and their families.

■ presentations for lemborexant:

poster session: p18, presentation date: monday june 10, 5:15pm – 7:15pm (local time)

	presentation title
poster number: 102 abstract: 0367	lemborexant treatment for insomnia: six-month safety
poster number: 105 abstract: 0368	efficacy and tolerability of lemborexant in female and male subjects with insomnia
poster number: 106 abstract: 0369	effect of lemborexant on sleep architecture in older adults with insomnia disorder
poster number: 107 abstract: 0370	patient-reported sleep onset and sleep maintenance: pooled analyses of lemborexant phase 3 studies
poster number: 108 abstract: 0371	lemborexant treatment for insomnia in phase 3: impact on disease severity
poster number: 103 abstract: 0429	respiratory safety of lemborexant in adult and elderly subjects with mild obstructive sleep apnea
poster number: 104 abstract: 0430	respiratory safety of lemborexant in healthy adult and elderly subjects
poster number: 022 abstract: 0056	samp8 mice as a preclinical model for irregular sleep-wake rhythm disorder and efficacy of the dual orexin (hypocretin) receptor antagonist lemborexant

separate from the poster presentations, eisai will host a symposium, an interactive dialogue on insomnia diagnostic and therapeutic decision making, which will be held on sunday, june 9, from 6:15pm – 8:30pm (local time).

media inquiries:
public relations department,
eisai co., ltd.
81-(0)3-3817-5120

[notes to editors]

1. about lemborexant

lemborexant is a novel investigational small molecule compound, discovered and developed by eisai, that inhibits orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptors 1 and 2). in individuals with normal daily sleep-wake rhythms, orexin signaling is believed to promote periods of wakefulness. in individuals with sleep-wake disorders, it is possible that orexin signaling that regulates wakefulness is not functioning normally, suggesting that inhibiting inappropriate orexin signaling may enable initiation and maintenance of sleep. eisai is investigating lemborexant as a potential treatment option for multiple sleep-wake disorders, such as insomnia.

additionally, a phase 2 clinical study of lemborexant in patients with irregular sleep-wake rhythm disorder (iswrd) and mild to moderate alzheimer’s dementia is underway.

2. about sleep disorders

several population studies show that sleep disorders affect many more people worldwide than previously thought.¹ insomnia disorder is the most common sleep disorder, with persistent insomnia symptoms experienced by approximately 30 percent of the adult population.^1,2 insomnia disorder is characterized by difficulty falling asleep, staying asleep, or both, despite an adequate opportunity to sleep, that can lead to daytime consequences such as fatigue, difficulty concentrating and irritability.^3,4

sleeping well is essential for good health, including brain health. poor sleep is associated with a wide range of health consequences, including an increased risk of hypertension, accidental injury, diabetes, obesity, depression, heart attack, stroke, dementia, as well as adverse effects on mood and behavior.^3,5

experimental studies in animals and humans provide evidence of associations between sleep and disease risk factors, diseases, and mortality.⁶ studies suggest an optimal sleep duration between seven and eight hours.⁷

women are 1.4 times more likely than men to suffer from insomnia.⁸ older adults also have higher prevalence of insomnia; aging is often accompanied by changes in sleep patterns, including disrupted sleep, frequent walking, and early waking, that can lead to less sleep time.⁹

¹ ferrie je, et al. sleep epidemiology – a rapidly growing field. int j epidemiol. 2011;40(6):1431–1437.
² roth t. insomnia: definition, prevalence, etiology and consequences. j clin sleep med. 2007;3(5 suppl):s7–s10.
³ institute of medicine. sleep disorders and sleep deprivation: an unmet public health problem. washington, dc: national academies press. 2006.
⁴ ohayon mm, et al. epidemiology of insomnia: what we know and what we still need to learn. sleep med rev. 2002;6(2):97-111.
⁵ pase mp, himali jj, grima na, et al. sleep architecture and the risk of incident dementia in the community. neurology. 2017;89(12):1244-1250.
⁶ cappuccio fp et al. sleep and cardio-metabolic disease. curr cardiol rep. 2017;19:110.
⁷ cappuccio fp et al. sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies. sleep. 2010;33(5):585-592.
⁸ roth t, et al. prevalence and perceived health associated with insomnia based on dsm-iv-tr; international statistical classification of diseases and related health problems, tenth revision; and research diagnostic criteria/international classification of sleep disorders, second edition criteria: results from the america insomnia survey. biol psychiatry. 2011;69:592– 600.
⁹ crowley, k. sleep and sleep disorders in older adults. neuropsychol rev. 2011;21(1):41-53.

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that presentations on a series of abstracts highlighting updates regarding its in-house discovered lenvatinib mesylate (product name: lenvima^®, “lenvatinib”, kinase inhibitor), eribulin mesylate (product name: halaven^®, “eribulin”, halichondrin class microtubule dynamics inhibitor), and morab-202 (antibody drug conjugate, adc) will be given at the 55th annual meeting of the american society of clinical oncology (asco), taking place in chicago, the united states, from may 31 to june 4, 2019. the latest information on h3b-6527 (fibroblast growth factor receptor 4 inhibitor) and h3b-6545 (selective estrogen receptor α covalent antagonist), which were discovered by eisai’s u.s. oncology precision medicine-focused research and development subsidiary h3 biomedicine inc., will also be highlighted in presentations at asco.

major poster presentations at this year’s meeting include highlights of the latest data from an ongoing phase i clinical study investigating eisai’s first adc morab-202 in patients with solid tumors in japan. morab-202 is a novel adc that combines eisai’s investigational anti-folate receptor α (fra) antibody farletuzumab with eisai’s in-house discovered anticancer agent eribulin as the payload.

eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. the company will continue to create innovation in the development of new drugs based on cutting-edge cancer research, as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

major poster presentations:

product	abstract title and scheduled presentation date and time (local time)
lenvatinib abstract no: 6081	influence of tumor size and eastern cooperative oncology group performance status (ecog ps) at baseline on patient (pt) outcomes in lenvatinib-treated radioiodine-refractory differentiated thyroid cancer (rr-dtc) *poster presentation* \| june 1 (sat), 1:15-4:15 pm
lenvatinib abstract no: tps5607	a phase 3 trial evaluating efficacy and safety of lenvatinib in combination with pembrolizumab in patients with advanced endometrial cancer *poster presentation* \| june 1 (sat), 1:15-4:15 pm
lenvatinib abstract no: tps9118	randomized, double-blind, phase 3 trial of first-line pembrolizumab platinum doublet chemotherapy (chemo) ± lenvatinib in patients (pts) with metastatic nonsquamous non-small-cell lung cancer (nsclc): leap-006 *poster presentation* \| june 2 (sun), 8:00-11:00 am
lenvatinib abstract no: tps4152	lenvatinib (len) plus pembrolizumab (pembro) for the first-line treatment of patients (pts) with advanced hepatocellular carcinoma (hcc): phase 3 leap-002 study *poster presentation* \| june 3 (mon), 8:00-11:00 am
lenvatinib abstract no: tps9594	lenvatinib (len) plus pembrolizumab (pembro) in patients (pts) with advanced melanoma previously exposed to anti–pd-1/pd-l1 agents: phase 2 leap-004 study *poster presentation* \| june 3 (mon), 8:00-11:00 am
eribulin abstract no: 2606	balixafortide (a cxcr4 antagonist) eribulin in her2 negative metastatic breast cancer (mbc): survival outcomes of the phase 1 trial *poster presentation* \| june 1 (sat), 8:00-11:00 am
morab-202 abstract no: 5544	first-in-human (fih) phase 1 (ph1) study of morab-202 in patients (pts) with advanced folate receptor alpha (fra)-positive solid tumors *poster presentation* \| june 1 (sat), 1:15-4:45 pm
h3b-6545 abstract no: 1052	molecular characterization and monitoring of patient ctdna in phase 1 study of h3b-6545 in er mbc *poster presentation* \| june 2 (sun), 8:00-11:00 am
h3b-6545 abstract no: 1059	phase 1 dose escalation of h3b-6545, a first-in-class highly selective erα covalent antagonist (serca), in women with er-positive, her2-negative breast cancer (hr bc) *poster presentation* \| june 2 (sun), 8:00-11:00 am
h3b-6527 abstract no: 4095	a phase 1 study of h3b-6527 in hepatocellular carcinoma (hcc) or intrahepatic cholangiocarcinoma (icc) patients (pts) *poster presentation* \| june 3 (mon), 8:00-11:00 am
h3b-6527 abstract no: 4121	h3b-6527 clinical biomarker assay development and characterization of hcc patient samples *poster presentation* \| june 3 (mon), 8:00-11:00 am

product

abstract title and scheduled presentation date and time (local time)

lenvatinib

abstract no: 6081

influence of tumor size and eastern cooperative oncology group performance status (ecog ps) at baseline on patient (pt) outcomes in lenvatinib-treated radioiodine-refractory differentiated thyroid cancer (rr-dtc)

poster presentation | june 1 (sat), 1:15-4:15 pm

lenvatinib

abstract no: tps5607

a phase 3 trial evaluating efficacy and safety of lenvatinib in combination with pembrolizumab in patients with advanced endometrial cancer

poster presentation | june 1 (sat), 1:15-4:15 pm

lenvatinib

abstract no: tps9118

randomized, double-blind, phase 3 trial of first-line pembrolizumab platinum doublet chemotherapy (chemo) ± lenvatinib in patients (pts) with metastatic nonsquamous non-small-cell lung cancer (nsclc): leap-006

poster presentation | june 2 (sun), 8:00-11:00 am

lenvatinib

abstract no: tps4152

lenvatinib (len) plus pembrolizumab (pembro) for the first-line treatment of patients (pts) with advanced hepatocellular carcinoma (hcc): phase 3 leap-002 study

poster presentation | june 3 (mon), 8:00-11:00 am

lenvatinib

abstract no: tps9594

lenvatinib (len) plus pembrolizumab (pembro) in patients (pts) with advanced melanoma previously exposed to anti–pd-1/pd-l1 agents: phase 2 leap-004 study

poster presentation | june 3 (mon), 8:00-11:00 am

eribulin

abstract no: 2606

balixafortide (a cxcr4 antagonist) eribulin in her2 negative metastatic breast cancer (mbc): survival outcomes of the phase 1 trial

poster presentation | june 1 (sat), 8:00-11:00 am

morab-202

abstract no: 5544

first-in-human (fih) phase 1 (ph1) study of morab-202 in patients (pts) with advanced folate receptor alpha (fra)-positive solid tumors

poster presentation | june 1 (sat), 1:15-4:45 pm

h3b-6545

abstract no: 1052

molecular characterization and monitoring of patient ctdna in phase 1 study of h3b-6545 in er mbc

poster presentation | june 2 (sun), 8:00-11:00 am

h3b-6545

abstract no: 1059

phase 1 dose escalation of h3b-6545, a first-in-class highly selective erα covalent antagonist (serca), in women with er-positive, her2-negative breast cancer (hr bc)

poster presentation | june 2 (sun), 8:00-11:00 am

h3b-6527

abstract no: 4095

a phase 1 study of h3b-6527 in hepatocellular carcinoma (hcc) or intrahepatic cholangiocarcinoma (icc) patients (pts)

poster presentation | june 3 (mon), 8:00-11:00 am

h3b-6527

abstract no: 4121

h3b-6527 clinical biomarker assay development and characterization of hcc patient samples

poster presentation | june 3 (mon), 8:00-11:00 am

media inquiries:
public relations department,
eisai co., ltd.

[notes to editors]
1. about the eisai and merck & co., inc., kenilworth, n.j., u.s.a. strategic collaboration
in march 2018, eisai and merck & co., inc., kenilworth, n.j., u.s.a., known as msd outside the united states and canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvima^®(lenvatinib). under the agreement, the companies will jointly develop, manufacture and commercialize lenvima, both as monotherapy and in combination with merck & co., inc., kenilworth, n.j., u.s.a.’s anti-pd-1 therapy keytruda^®(pembrolizumab).

in addition to ongoing clinical studies evaluating the lenvima and keytruda combination across several different tumor types, including renal cell carcinoma, the companies will jointly initiate new clinical studies through the leap (lenvatinib and pembrolizumab) clinical program, which will evaluate the combination to support 11 potential indications in six types of cancer (endometrial cancer, hepatocellular carcinoma, melanoma, non-small cell lung cancer, squamous cell carcinoma of the head and neck, and urothelial cancer). the leap clinical program also includes a new basket trial targeting six additional cancer types (biliary tract cancer, breast cancer, colorectal cancer, gastric cancer, glioblastoma and ovarian cancer). the lenvima and keytruda combination is not approved in any cancer types today.

keytruda^® is a registered trademark of merck sharp & dohme corp., a subsidiary of merck & co., inc., kenilworth, n.j., usa.

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