news – page 15 – eisai china lnc.-pg电子app

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) and fuji yakuhin co., ltd. (headquarters: saitama, ceo: masayuki takayanagi, “fuji yakuhin”) announced today that they have concluded a license agreement concerning dotinurad (generic name), a treatment for hyperuricemia and gout discovered by fuji yakuhin, for development and distribution in china.

based on this agreement, eisai will acquire exclusive development and marketing rights for dotinurad in china from fuji yakuhin. fuji yakuhin will retain responsibility for manufacturing the formulation of dotinurad, and supply to eisai. eisai will be responsible for a new drug application for dotinurad  in china and pay fuji yakuhin upfront payment, development milestone and sales milestone.

hyperuricemia is the second most common metabolic disease after diabetes mellitus in china. in addition, hyperuricemia is known to be associated with various diseases in the urinary system, endocrine system, metabolic system, cardio-cerebrovascular system etc., including gout. furthermore, it is estimated that currently in china, the number of patients with hyperuricemia is approximately 190 million and the number of patients with gout is approximately 16 million.¹ it is expected that the number of patients will further increase in the near future due to changes in lifestyle and dietary preferences in accordance with socioeconomic development in china.
dotinurad is a new therapeutic agent for gout and hyperuricemia discovered by fuji yakuhin. dotinurad suppresses uric acid reabsorption and lowers blood uric acid levels, by selectively inhibiting the urate transporter (urat1) related to reabsorption of uric acid in the kidney.

under this agreement, eisai will proceed with the development of dotinurad in china. following commercialization, eisai will aim to contribute to patients with hyperuricemia that is unmet medical needs by utilizing the knowledge and networks that eisai has cultivated through its china business. fuji yakuhin anticipates maximizing the value of dotinurad in china by leveraging eisai’s business base as the first step in the global expansion of dotinurad. through the development and commercialization of dotinurad, eisai and fuji yakuhin will provide new treatment options for hyperuricemia and gout in china and contribute to improving the quality of life of patients.

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references:
¹ for the estimated data regarding the number of patients with hyperuricemia as well as the number of patients with gout:data of morbidity prevalence rate – rui liu et al., prevalence of hyperuricemia and gout in mainland china from 2000 to 2014: a systematic review and meta-analysis, biomed research international, volume 2015, article id 762820
estimated data calculated from united nations world population estimates – world population prospects, url：

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that it has launched the in-house developed anticancer agent halaven^® (product name in china: 海乐卫^®, generic name: eribulin mesylate) in china.

halaven 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 halaven’s unique actions on the tumor microenvironment such as increasing vascular perfusion and permeability in tumor cores,¹ promotion of the epithelial state and decrease in the capacity of breast cancer cells to migrate.² in a phase iii clinical study (embrace) of halaven versus treatment of physician’s choice (tpc) in 762 patients with advanced or recurrent breast cancer previously treated with an anthracycline and a taxane, halaven showed an extended overall survival compared to tpc.³ for use in the treatment of breast cancer, halaven is currently approved in over 70 countries worldwide, including the united states, japan and countries in europe and asia. the most common adverse events (incidence 25% and higher) in the halaven arm of this study were asthenia (fatigue), neutropenia, alopecia, peripheral neuropathy, nausea and constipation.

in china, halaven received new drug approval for the use in the treatment of patients with locally advanced or metastatic breast cancer, previously treated with at least two prior chemotherapy regimens, including and an anthracycline and a taxane in july 2019 based on the results of study 304,⁴ which was a phase iii clinical study in 530 women with locally recurrent or metastatic breast cancer, previously treated with chemotherapy regimens, including an anthracycline and a taxane. halaven demonstrated a statistically significant extension of progression-free survival over the comparator treatment vinorelbine. the five most common adverse events observed in the halaven arm of this study were white blood cell count decreased, neutrophil count decreased, increased aspartate aminotransferase, increased alanine aminotransferase and anemia.

the number of women diagnosed with breast cancer in china has increased in recent years,⁵ with an estimated 370,000 new cases of breast cancer and 100,000 related deaths in 2018.⁶ breast cancer is now the most frequently diagnosed cancer in chinese women.⁶

eisai positions oncology as a key therapeutic area, and is aiming to create revolutionary new medicines with the potential to cure cancer. lenvima^® has been available in china as a treatment of patients with unresectable hepatocellular carcinoma who have not received prior systematic therapy since november 2018.* with this approval of halaven, 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.

*eisai and merck & co., inc., kenilworth, n.j., u.s.a’s chinese subsidiary msd china have been providing information about lenvima in china.

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1. about halaven (generic name: eribulin mesylate)
halaven is in the halichondrin class of microtubule dynamics inhibitors with a novel mechanism of action. structurally, halaven is a simplified and synthetically produced version of halichondrin b, a natural product isolated from the marine sponge halichondria okadai. halaven is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division. in addition, non-clinical studies showed halaven’s unique actions in the tumor microenvironment such as an increase in vascular perfusion and permeability in tumor cores,¹ promotion of the epithelial state, decrease in capacity of breast cancer cells to migrate,² and etc.

halaven was first approved as a treatment in the united states in november 2010 for patients with metastatic breast cancer. halaven is currently approved for use in the treatment of breast cancer in over 70 countries worldwide, including japan, china and countries in europe, the americas and asia. furthermore, halaven was first approved as a treatment for soft tissue sarcoma in the united states in january 2016, and is approved in over 65 countries including japan and in europe and asia. furthermore, halaven has been designated as an orphan drug for soft tissue sarcoma in the united states and japan.

specifically, halaven 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.

¹ 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
² 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
³ cortes j et al., eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (embrace): a phase 3 open-label randomised study lancet, 2011; 377, 914-23
⁴ 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
⁵ lei f et al., breast cancer in china. the lancet oncology, 2014; 15(7), e279–e289
⁶ ferlay j, et al., (2018). global cancer observatory: cancer today. lyon, france: international agency for research on cancer. , as of january 10, 2020

 

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) today announced that the u.s. food and drug administration (fda) approved the new drug application for its in-house discovered and developed orexin receptor antagonist dayvigo^tm(lemborexant). dayvigo was approved for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults¹. in the united states, dayvigo will be commercially available in 5 mg and 10 mg tablets following scheduling by the u.s. drug enforcement administration (dea), which is expected to occur within 90 days.

the mechanism of action of lemborexant in the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance is presumed to be through antagonism of orexin receptors. the orexin neuropeptide signaling system plays a role in wakefulness. blocking the binding of wake-promoting neuropeptides orexin a and orexin b to orexin receptors ox1r and ox2r is thought to suppress wake drive. lemborexant binds to orexin receptors ox1r and ox2r and acts as a competitive antagonist with stronger inhibition effect to ox2r*.

the approval was based on the results of a clinical development program that included two pivotal phase iii studies (sunrise 2 and sunrise 1), which evaluated dayvigo versus comparators for up to one month and dayvigo versus placebo for six-months, respectively, in a total of about 2,000 adult patients with insomnia. from these studies results, dayvigo demonstrated statistically significant superiorities on sleep onset and sleep maintenance compared to placebo in both subjective and objective evaluations.

across sunrise 2 and sunrise 1, dayvigo was not associated with rebound insomnia following treatment discontinuation, and there was no evidence of withdrawal effects following dayvigo discontinuation at either dose. in addition, the development program included multiple safety studies evaluating effects on postural stability, cognition, driving performance and respiratory safety.

• sunrise 2 was a long-term (six month), randomized, double-blind, placebo-controlled, multi-center, trial in adult patients age 18 or older who met dsm-5** criteria for insomnia disorder. patients were randomized to placebo (n=325), dayvigo 5 mg (n=323), or dayvigo 10 mg (n=323) once nightly. the primary efficacy endpoint was the mean change from baseline to end of treatment at six months for patient-reported (subjective) sleep onset latency (ssol), defined as the estimated minutes from the time that the subject attempted to sleep until falling asleep. pre-specified secondary efficacy endpoints were change from baseline to end of treatment at six months for patient reported sleep efficiency (sse; defined as the proportion of time spent asleep during time in bed) and subjective sleep onset and sleep maintenance (swaso; defined as the minutes of wake from the onset of persistent sleep until lights on). the primary and pre-specified secondary efficacy endpoints were measured using a sleep diary. in sunrise 2, dayvigo 5 mg and 10 mg demonstrated statistically significant superiority on the primary efficacy measure, ssol, compared to placebo. dayvigo 5 mg and 10 mg also showed statistically significant superiority in sse and swaso.¹
• sunrise 1 was a short-term (one month), randomized, double-blind, placebo- and active-controlled, multi-center, parallel-group clinical trial in adult female subjects age 55 and older and male subjects 65 years and older who met dsm-5 criteria for insomnia disorder. patients were randomized to placebo (n=208), dayvigo 5 mg (n=266) or 10 mg (n=269) or active comparator (n=263) once nightly. the primary efficacy endpoint was the mean change in latency to persistent sleep (lps; defined as the number of minutes from lights off to the first 10 consecutive minutes of non-wakefulness) from baseline to end of treatment (day 29/30), as measured by overnight polysomnography (psg) monitoring. the pre-specified secondary efficacy endpoints in sunrise 1 were the mean change from baseline to end of treatment (day 29/30) in sleep efficiency (se) and wake after sleep onset (waso) measured by psg. in sunrise 1, dayvigo 5 mg and 10 mg demonstrated statistically significant superiority on the primary efficacy measure, lps, compared to placebo. dayvigo 5 mg and 10 mg demonstrated statistically significant improvement in se and waso compared to placebo.¹

the most common adverse reaction (reported in 5% or more of patients treated with dayvigo and at least twice the rate of placebo) in sunrise 2 (the first 30 days) and sunrise 1 was somnolence (dayvigo 10 mg, 10%; dayvigo 5 mg, 7%; placebo, 1%).

in addition to these pivotal trials, eisai conducted a number of studies to further evaluate the safety of dayvigo, including a study that assessed the effect of dayvigo on postural stability and cognitive performance and a next-morning driving study.

• middle of the night safety (study 108): the effect of dayvigo on middle of the night safety was evaluated in a randomized, placebo- and active-controlled trial in healthy female subjects ≥ age 55 or male subjects ≥ age 65. postural stability, the ability to awaken in response to a sound stimulus, and attention and memory were assessed following a scheduled awakening four hours after the start of the eight-hour time in bed. nighttime dosing of dayvigo 5 and 10 mg resulted in impairment of balance (measured by body sway area) at four hours as compared to placebo. there were no meaningful differences between dayvigo (5 or 10 mg) and placebo on ability to awaken to sound. dayvigo was associated with dose-dependent worsening on measures of attention and memory as compared to placebo.¹
• effects on next-day postural stability and attention and memory (sunrise1 and study 108): the effects of dayvigo on next day postural stability and attention and memory were evaluated in two randomized, placebo- and active-controlled trials in healthy subjects and insomnia patients age 55 and older. there were no meaningful differences between dayvigo (5 or 10 mg) and placebo on next-day postural stability, or memory compared to placebo. ¹
• effects on driving (study 106): a randomized, double-blind, placebo- and active-controlled, four-period crossover study evaluated the effects of nighttime administration of dayvigo on next-morning driving performance approximately nine hours after dosing in 24 healthy elderly subjects (≥65 years old, median age 67 years) and 24 adult subjects (median age 49 years). although dayvigo at doses of 5 and 10 mg did not cause statistically significant impairment in next-morning driving performance in adult or elderly subjects (compared with placebo), driving ability was impaired in some subjects taking 10 mg dayvigo.

“insomnia disorder is a chronic condition that has a variety of potential negative impacts and long-term consequences for health and well-being,”² said russell rosenberg, phd, d.absm, a principal investigator in the dayvigo clinical studies and former chairman of the board of the national sleep foundation. “the clinical trials provide evidence that dayvigo may improve patients’ ability to fall asleep and stay asleep.”

“we believe the approval of dayvigo is particularly exciting because it is the first fda-approved medication to report safety data over a 12-month period along with sleep onset and sleep maintenance efficacy data over a six-month period in a pivotal clinical study,” said lynn kramer, md, chief clinical officer, neurology business group, eisai. “we look forward to making this new therapeutic option available to the millions of patients who suffer with insomnia.

eisai has submitted new drug applications seeking approval of this agent for use in the treatment of insomnia in japan (march 2019) and canada (august 2019).

insomnia 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.^2,9 insomnia is one of the most common sleep-wake disorders with high prevalence. approximately 30% of adults worldwide have symptoms of insomnia,^7,8 and many of them remain months to years. as a result, insomnia causes various social losses such as long absences and reduced productivity.

with dayvigo and through its research and development efforts focusing on orexin biology, eisai aspires to improve the lives of patients suffering from sleep disorders.

*lemborexant binds to orexin receptors, ox1r and ox2r and acts as a competitive antagonist (ic₅₀ values of 6.1 nm and 2.6 nm, respectively). when activated, the role of ox1r is to suppress rem sleep, and the role of ox2r is to suppress both non-rem sleep and rem sleep. lemborexant enables sleep by preventing activation of ox1r and ox2r.
**dsm-5: diagnostic and statistical manual of mental disorders, fifth edition (american psychiatric association)

 

media inquiries:
public relations department,
eisai co., ltd.
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[notes to editors]
1. about lemborexant
lemborexant is eisai’s in-house discovered and developed small molecule that binds to orexin receptors, ox1r and ox2r and acts as a competitive antagonist (ic50 values of 6.1 nm and 2.6 nm, respectively). the mechanism of action of lemborexant in the treatment of insomnia is presumed to be through antagonism of orexin receptors. the orexin neuropeptide signaling system plays a role in wakefulness. blocking the binding of wake-promoting neuropeptides orexin a and orexin b to receptors ox1r and ox2r is thought to suppress wake drive.
as a result of clinical studies, the effect of lemborexant are suggested not only for primary insomnia but also for insomnia which is associated with other diseases, such as depression, (sunrise-1 and sunrise-2).
in addition to the indication of insomnia, a phase ii clinical study of lemborexant in patients with iswrd associated with mild to moderate alzheimer’s dementia is underway.

2. about sleep-wake disorders and insomnia
sleep-wake disorders consist of disease categories such as insomnia, iswrd, hypersomnia and breathing-related sleep disorders. among the sleep-wake disorders, insomnia is the most common with persistent insomnia symptoms experienced by approximately 30 percent of the adult population worldwide.^7,8 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.^2,9
good quality sleep is essential for good health including brain health,¹¹ and studies suggest an optimal sleep duration between seven and eight hours.¹² 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.^2,10
women are 1.4 times more likely than men to suffer from insomnia.¹³ older adults also have higher prevalence of insomnia; aging is often accompanied by changes in sleep patterns, including disrupted sleep, frequent waking, and early waking, that can lead to less sleep time.¹⁴ 

3. sunrise 2 (study 303)⁴
sunrise 2 is a 12-month multicenter, global (japan, north america, south america, europe, asia, and oceania), randomized, placebo-controlled, double-blind, parallel group phase iii study of 949 male or female adult participants (18 to 88 years of age) with insomnia disorder. sunrise 2 included a pre-randomization phase of up to 35 days (including a two-week placebo run-in period) and a randomization phase comprised of a six-month placebo-controlled treatment period, a six-month period of only active treatment, and a two-week period without treatment prior to the end-of-study-visit. lemborexant 5 mg, 10 mg or matching placebo was taken orally in tablet form at home each night immediately before the patient intended to try to sleep for the first six months of study. patients who received placebo during the first six-month period were administered lemborexant 5 mg or 10 mg for the second six-month period. patients who received active treatment during the first period continued on the treatment to which they were originally randomized.
the primary outcome measure was mean change from baseline in subjective sleep onset latency after six months of placebo-controlled treatment. key secondary outcome measures were mean change from baseline in subjective sleep efficiency and subjective wake after sleep onset after six months of placebo-controlled treatment.
from the results, the primary endpoint and all secondary endpoints for efficacy were achieved for lemborexant arms, and statistically significant improvements in sleep onset and sleep maintenance were confirmed for lemborexant  arms compared to placebo during the six-month treatment period. the common aes in the lemborexant arms were somnolence, nasopharyngitis, headache and influenza.

4. sunrise 1 (study 304)³
sunrise 1 is a multicenter, randomized, double-blind, placebo-controlled, active comparator, parallel-group phase iii study of the efficacy and safety of lemborexant in 1,006 patients 55 years and older (45% of all patients were aged 65 years and older) with insomnia disorder conducted in north america and europe. sunrise 1 included a pre-randomization phase of up to 35 days (including a two-week placebo run-in period) and a randomization phase comprised of a 30-day treatment period and a two-week period without treatment prior to the end-of-study-visit. in this study, patients were administered placebo or one of three treatment regimens (lemborexant 5 mg, lemborexant 10 mg, zolpidem er 6.25 mg).
the primary objective for sunrise 1 was to demonstrate using polysomnography that lemborexant  at either the 5 mg or 10 mg dose is superior to placebo on objective sleep onset, as measured by latency to persistent sleep after the last two nights of one month of treatment. key secondary endpoints included change from baseline in sleep efficiency for both lemborexant  doses compared to placebo, wake after sleep onset (waso) for both lemborexant  doses compared to placebo, and waso in the second half of the night (waso2h) for both lemborexant  doses compared to zolpidem er, after one month of treatment, measured objectively by polysomnography.
the results of the study showed that lemborexant  had statistically significant improvement compared to zolpidem er 6.25 mg and placebo in sleep parameters evaluated in primary and key secondary endpoints. the common adverse events (aes) in the dayvigo arms were headache and somnolence.

5. about study 106⁵
study 106 was a randomized, double-blind, placebo- and active-controlled, four period, crossover phase i study to evaluate the effect of lemborexant in 48 healthy adults and elderly volunteers (23 to 58 years of age, mean: 58.5 years old) to evaluate on-road driving performance. volunteers (65 years and older: 24, 23 to 64 years old: 24) were treated at bedtime with two out of three dose levels of lemborexant (2.5, 5 or 10 mg) and placebo for eight consecutive days. zopiclone 7.5 mg as an active control was administered on days one and eight only, with placebo given for the six days in between. the primary endpoint was to evaluate change of standard deviation of lateral position (sdlp) during an on-road driving test conducted after the first (in the morning of day 2) and last day (in the morning of day 9) of treatment administration after 9-hour dose.
in the on-road test, the volunteers drove a specially instrumented vehicle for about one hour over 100km (approximately 60 miles) primary highway circuit, accompanied by a licensed driving instructor. the task was to drive with a steady lateral position between the delineated boundaries of the slower traffic lane, while maintaining a constant speed of 95km/h.
although lemborexant at doses of 5 and 10 mg did not cause statistically significant impairment in next-morning driving performance in adult or elderly subjects (compared with placebo), driving ability was impaired in some subjects taking 10 mg lemborexant.

6. about study 108⁶
study 108 was a randomized, double-blind, four period crossover phase i study to evaluate the effect of lemborexant on postural stability, auditory awakening threshold, and cognitive performance in 56 healthy volunteers 55 years and older. participants were treated at bedtime with a single dose of placebo, lemborexant 5 mg, lemborexant 10 mg, or zolpidem er 6.25 mg. the primary endpoint assessed postural stability when awakened by an alarm approximately four hours after administration of lemborexant compared to zolpidem er, as measured by stabilometer.

while there was a statistically significant increase in body sway for both doses of lemborexant compared with placebo, zolpidem er increased body sway at a magnitude almost three times more than lemborexant. this increase with zolpidem was three times that, which is associated with a blood alcohol content (bac 0.05 percent) near the legal driving limit.

the next morning, shortly after the end of eight hours in bed, unlike zolpidem er, neither dose of lemborexant had statistically significant residual effects on this measure of postural stability as compared to placebo.

¹ eisai inc. dayvigo full prescribing information. 2019.
² institute of medicine. sleep disorders and sleep deprivation: an unmet public health problem. washington, dc: national academies press. 2006.
³ eisai inc. a multicenter, randomized, double-blind, placebo-controlled, active comparator, parallel-group study of the efficacy and safety of lemborexant in subjects 55 years and older with insomnia disorder. (e2006-g000-304). (clinicaltrials.gov identifier nct02783729). 2018. unpublished data on file.
⁴ eisai inc. a long-term multicenter, randomized, double-blind, controlled, parallel-group study of the safety and efficacy of lemborexant in subjects with insomnia disorder (e2006-g000-303). (clinicaltrials.gov identifier nct02952820). 2018. unpublished data on file.
⁵ eisai inc. a randomized, double-blind, placebo- and active-controlled, 4-period crossover study to evaluate the effect of dayvigo versus placebo on driving performance in healthy adult and elderly subjects. (e2006-e044-106). (clinicaltrials.gov identifier nct02583451). 2017. unpublished data on file.
⁶ eisai inc. a randomized, double-blind, placebo-controlled and active-comparator, 4-period crossover study to evaluate the effect of dayvigo versus placebo and zolpidem on postural stability, auditory awakening. (e2006-a001-108). (clinicaltrials.gov identifier nct03008447). 2017. unpublished data on file.
⁷ ferrie je, et al. sleep epidemiology – a rapidly growing field. int j epidemiol.2011;40(6):1431–1437.
⁸ roth t. insomnia: definition, prevalence, etiology and consequences. j clin sleep med. 2007;3(5 suppl):s7–s10.
⁹ 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.
¹⁰ 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.
¹¹ cappuccio fp, et al. sleep and cardio-metabolic disease. curr cardiol rep. 2017;19:110.
¹² 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.
¹³ 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.
¹⁴ crowley k. sleep and sleep disorders in older adults. neuropsychol rev.2011;21(1):41-53.

the content presented at the 13th clinical trials on alzheimer’s disease (ctad) conference

 

sysmex corporation (hq: kobe, japan; chairman and ceo: hisashi ietsugu; “sysmex”) and eisai co., ltd. (hq: tokyo, japan; ceo: haruto naito; “eisai”) announced that the most recent data from the project to develop a method of diagnosing alzheimer’s disease (ad) using blood plasma was presented at the 13th clinical trials on alzheimer’s disease (ctad) conference, held virtually from november 4 to 7, 2020. sysmex demonstrated on behalf of the two companies the performance of the amyloid beta (aβ) in plasma measured on sysmex’s hiscl^tm fully automated immunoassay analyzers in predicting amyloid pathology as defined by amyloid positron emission tomography (pet) imaging on the centiloid scale.¹

 

the total number of those living with dementia across the world is projected to reach 82 million in 2030 and 152 million in 2050, with the total global societal cost of dementia stemming from direct medical and social care costs and lower productivity being estimated to reach 2 trillion usd in 2030.⁶ in japan, the number of those with dementia is thought to have reached approximately 4.62 million in 2012 and is projected to grow to 7.30 million in 2025⁷, with the total societal cost of this disease being estimated to be equivalent to 4.1%⁸ of the gross domestic product (gdp) in 2025 (25.8 trillion yen⁹). of these sufferers, those living with ad are thought to account for more than 60% of those living with dementia.⁷

it is conceivable that ad is a disease that results in synaptic dysfunction and neuronal cell death due to tau deposition in neurons triggered by aβ aggregation on the outside of neurons. these brain changes cause cognitive impairment and psychological and behavioral symptoms, suggesting that the aβ aggregation and accumulation inside the brain is caused by ad before the presence of cognitive impairment appears, thus, it is believed that early diagnosis and early intervention is more effective in therapies targeting aβ. currently, amyloid pet and aβ ratio in cerebrospinal fluid (csf) are used for detecting amyloid aggregates in the brain, but this puts significant burden on patients in terms of access, costs, and their physical wellbeing.¹⁰

sysmex and eisai are working to create new diagnostic technologies for the prevention and treatment of dementia. accordingly, the overarching aim is to contribute to the advancement of healthcare and improve the quality of life for those living with the disease and their families.

 

terminology
1. a standardization scale for integration analysis of pet suvr values as measured by different amyloid pet imaging probes.
2. trained doctors qualitatively distinguish amyloid pet positive from amyloid negative subjects by visually reading images.
3. klunk we et al, alzheimer’s dementia (2014)
4. assesses how correlated two sets of data are based on two quantitative data distributions. for the purpose of this analysis, spearman’s rank correlation coefficient (rs), which is a correlation index as determined by the rankings of the two variables, was calculated.
5. schindler se et al, neurology (2019)
6. world alzheimer report 2018
7. promotion of comprehensive measures against dementia, ministry of health, labour and welfare
8. study on economic impact of dementia in japan, 2014 health labour sciences research grant annual report
9. estimated by sysmex based on japan’s medium-term economic outlook (february 2018), daiwa institute of research
10. aβ is a peptide made of amino-acid residues removed from amyloid precursor protein. many of them are aβ_1-40, which is comprised of 40-residues, and the aβ_1-40 level does not fluctuate significantly as ad progresses. comprised of 42-residues, aβ_1-42, on the other hand, is highly cohesive and decreases in cerebrospinal fluid (csf) from the early stages of ad. it is believed that aβ’s absolute values show individual and intrinsic variability but that the plasma aβ_1-42/aβ_1-40 ratio remains unchanged. it has also been reported that the plasma aβ_1-42/aβ_1-40 ratio in csf shows a high correlation with amyloid pet.

about the collaboration between sysmex and eisai

in february 2016, sysmex and eisai signed a comprehensive non-exclusive agreement aimed at the development of new diagnostic tests in the field of dementia. by leveraging each other’s technologies and knowledge, the objective has been to discover next-generation diagnostic reagents that will enable early diagnosis of dementia, selection of the most appropriate treatment options, and regular monitoring of the effects of such treatments. at the 12th ctad held in december 2019, the two companies reported on the performance of the plasma aβ ratio measured on a fully automated immunoassay system hiscl in predicting the amyloid pet scan results (sensitivity: 73%, specificity: 71% [auc = 0.74]), thus demonstrating the potential to predict amyloid pathology in the brain using the plasma aβ ratio.^* this finding was expected to lead to the development of a simple method of diagnosing alzheimer’s disease using blood.
^*

 

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eisai co., ltd.
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tel：03-3817-5120

information contained in the press release is current as of the date of the announcement but may be subject to change without prior notice.