news – page 18 – eisai china lnc.-pg电子app

news – page 18 – eisai china lnc.-pg电子app

eisai co.,ltd.(headquarters: tokyo, ceo: haruo naito, “eisai”) announced that data relating to a new anti-tau antibody e2814*1 was 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.: p4-696).

neurofibrillary tangles composed of aggregated tau protein is one of the pathological features of alzheimer’s disease (ad). during the course of the disease, tau is believed to spread throughout the brain via synaptically-connected pathways. the propagation of this pathology is thought to be mediated by tau species (“seeds”) containing the microtubule binding region of tau (mtbr). e2814 is designed to target mtbr containing tau species, preventing build-up and spreading of tau seeds, and thus may slow the course of the disease.

the data presented describes a method for quantification of mtbr-containing tau fragments mtbr in cerebrospinal fluid (csf) from patients with ad. in addition, an e2814 target engagement biomarker assay is binding to fragments including mtbr of e2814 target with this assay in the clinical study.

the results confirmed that mtbr-containing tau species can be quantified in human csf and there was a significant increase in mtbr in csf of patients with ad (caucasian aged between 64 and 84, mmse: 13-26) in comparison with healthy adults (caucasian aged between 46 and 75) (p<0.0001). furthermore, mtbr-containing tau species in the csf of ad patients was well correlated with phosphorylated tau (r2 = 0.8849) rather than total tau (r2 = 0.7811), maybe indicating the pathological species for tau propagation.

in vitro experiments using csf from patients with ad spiked with e2814, showed that e2814 was able to bind the majority of mtbr-containing tau in the samples. additionally, in vivo experiments in non-human primates demonstrated dose-dependent binding of e2814 to mtbr-containing tau fragments in csf samples and a concomitant reduction in free mtbr-containing tau species.

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 e2814 is the first clinical candidate discovered as part of a research collaboration with university college london in uk.

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

[notes to editors]
1. about e2814
an investigational anti-tau monoclonal antibody. e2814 is being developed as a disease modifying agent for alzheimer’s disease and other tauopathies, phase i clinical studies are under preparation. the clinical candidate was discovered as part of the research collaboration between eisai and university college london. e2814 is designed to prevent the spreading of tau seeds within the brains of affected individuals.

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 its latest research on evaluation about correlation of amyloid beta (aβ) in plasma and in cerebrospinal fluid (csf) by high precision measurement with the newly developed automated protein assay system, jointly developed with sysmex corporation (headquarters: hyogo, chairman and ceo: hisashi ietsugu, “sysmex”), using full-automated immunoassay system hiscltm*1 series for creating the simplified diagnosis of alzheimer’s disease (ad) with blood was 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.: p4-548)

aβ is a peptide consisting of amino acid residues, which is generated by excision from the amyloid precursor protein.  aβ1-40 consisting of 40 residues is dominant substance, and aβ1-40 does not significantly fluctuate with progression of ad. on the other hand, as for the aβ1-42 consisting of 42 residues, the aggregability is high and the reduction in aβ1-42 is detected from the early stage of ad. the absolute value of aβ has individual differences and intra individual variabilities, therefore, aβ1-42/aβ1-40 ratio in csf is used for the diagnosis of amyloid positive or negative.

in this research, the correlation between aβ1-42/aβ1-40 ratio in plasma and aβ1-42/aβ1-40 in csf were investigated for creating a simple blood diagnostic for ad by the automated protein assay system using full-automated immunoassay system hiscl™series. this assay system enables the automated immune assay in 17 minutes with small volume samples such as 10-30µl, and aβ assay in plasmas is possible with enough sensitivity and the high reliability. the samples from elderly person with normal cognition and patients with mild cognitive impairment (mci) and ad were used for investigation with hiscl™ series. results show a correlation (spearman’s rank correlation coefficient (rs) *2 =0.502, p<0.001) between aβ1-42/aβ1-4 ratio in plasma and aβ1-42/aβ1-40 ratio in csf; therefore, it may be possible to understand the pathological processes in the brain condition by measuring aβ1-42/aβ1-40 ratio in plasma. to further assess clinical utility, eisai aim to check the correlation between aβ1-42/aβ1-40 ratio in plasma and amyloid pet.

eisai aims to realize the prevention and cure of dementia including establishment of new diagnostics by 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 further contribute to addressing the unmet medical needs of, as well as increasing the benefits provided to, patients and their families.

 

*1 hiscl™ is a trademark of sysmex corporation.

*2 the correlation coefficient indicates the strength of the relationship between the two data from the two quantitative data distributions. in this analysis, spearman’s rank correlation coefficient (rs) which is an index of correlation obtained from rank data is calculated.

 

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

 

[notes to editors]
1. about collaboration between eisai and sysmex
eisai and sysmex have entered into a comprehensive non-exclusive collaboration agreement aimed at the creation of new diagnostics in the field of dementia in february, 2016. leveraging each other’s technologies and knowledge, the two companies aim to discover next-generation diagnostics that will enable early diagnosis, selection of treatment options and the regular monitoring of the effects of treatment for dementia.

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).

 

yuan 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
lei 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  
funahashi y et al., eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models. cancer sci., 2014; 105, 1334-1342
yoshida 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 33rd 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


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.

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