news – page 19 – eisai china lnc.-爱游戏(ayx)中国官方网站

news – page 19 – eisai china lnc.-爱游戏(ayx)中国官方网站

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

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.

eisai to continue to develop and commercialize lemborexant globally

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announces today that its u.s. subsidiary eisai inc. has bought out purdue pharma l.p.’s rights in the worldwide collaboration for the development and commercialization of 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) in patients with alzheimer’s disease. eisai group will solely conduct the development and the commercialization of lemborexant globally.

discovered by eisai, lemborexant is an investigational dual orexin receptor antagonist. the u.s. food and drug administration (fda) accepted the new drug application (nda) for lemborexant for use in the treatment of insomnia disorders for review in march 2019 and set a prescription drug user fee act (pdufa) date for december 27, 2019. for japan, a marketing authorization application for lemborexant for use in the treatment of insomnia disorder has been submitted to the pharmaceuticals and medical devices agency (pmda) in march 2019 and is currently under review. furthermore, a phase ii clinical study of lemborexant for iswrd in patients with alzheimer’s disease is ongoing.

through lemborexant, eisai is striving to address unmet medical needs and contribute to further increasing the benefits for patients with sleep disorders and their families.

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 in-house scientists, that inhibits orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptor 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. 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.

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that the latest data on its dual orexin receptor antagonist lemborexant and its antiepileptic drug (aed) perampanel (product name: fycompa®) will be presented at the 2019 annual american academy of neurology (aan) meeting to be held from may 4 to 10, 2019 in philadelphia, pennsylvania in the united states.

as major presentations, an oral presentation will be given on the next-morning residual effects of lemborexant from the results of three placebo-controlled, active comparator, randomized, double-blind clinical studies evaluating on-road driving performance as well as postural stability, and memory and attention performance directly after awakening.
regarding perampanel, a total of 18 poster presentations will be given, including on the final analysis results from a phase iii clinical study (study 311) in pediatric patients aged 4 to 12 years old with epilepsy, as well as on inpatient hospitalization risk in patients with epilepsy before and after perampanel treatment.

eisai considers neurology a therapeutic area of focus, and strives to maximize the value of lemborexant and perampanel to further contribute to addressing the diverse needs of, as well as increasing the benefits provided to, patients and their families.

oral presentation: 

presentation number and scheduled presentation date (local time) abstract title
session 46:sleep science and therapy updates

thursday may 9
poster presentation: 13:00-15:00

effects of lemborexant in the morning: results from 3 randomized studies


poster presentation: 

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

poster number: 5-009

poster session: p1
sun
day may 5
poster presentation: 17:30-18:30

symptoms and impacts in epilepsy: findings from qualitative patient interviews

poster number: 5-021

poster session: p1
sun
day may 5
poster presentation: 17:30-18:30

safety and efficacy of adjunctive perampanel in younger (aged 4 to <7 years) and older (7 to <12 years) pediatric patients with partial-onset seizures (pos) or primary generalized tonic-clonic seizures (pgtcs) : final results from the 311 core study

poster number: 5-024

poster session: p1
sun
day may 5
poster presentation: 17:30-18:30

a post-marketing observational study to evaluate the safety and tolerability of perampanel as add-on therapy in patients with epilepsy aged ≥12 years

poster number: 5-029

poster session: p1
sun
day may 5
poster presentation: 17:30-18:30

pharmacokinetic (pk) assessment of perampanel intravenous (iv) formulation as a bioequivalent alternative to oral tablet administration

poster number: 5-001

poster session: p3
tues
day may 7
poster presentation: 17:30-18:30

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

poster number: 5-002

poster session: p3
tuesday
 may 7
poster presentation: 17:30-18:30

risk of hospitalization in patients with uncontrolled epilepsy treated with a long versus short half-life adjunctive antiepileptic medication

poster number: 5-005

poster session: p3
tues
day may 7
poster presentation: 17:30-18:30

perampanel use in established, refractory, and super-refractory status epilepticus (se): a summary of cases from austria, finland, germany, and spain

poster number: 5-007

poster session: p3
tues
day may 7
poster presentation: 17:30-18:30

effect of concomitant enzyme-inducing antiepileptic drugs (eiaeds) 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 number: 5-017

poster session: p3
tues
day may 7
poster presentation: 17:30-18:30

phase ii, open-label pharmacokinetic (pk) study of perampanel oral suspension as adjunctive therapy in pediatric patients (aged ≥1 to <24 months) with epilepsy: study 238 design and preliminary safety data
poster number: 5-018

poster session: p3
tuesday
 may 7
poster presentation: 17:30-18:30

inpatient hospitalizations rates in patients diagnosed with epilepsy and treated with perampanel or lacosamide
poster number: 5-019

poster session: p3
tues
day may 7
poster presentation: 17:30-18:30

study 410 enrollment update: multicenter, open-label, phase iv study of perampanel as monotherapy or first adjunctive therapy in patients with partial-onset seizures (pos) or primary generalized tonic-clonic seizures (pgtcs)
poster number: 5-022

poster session: p3
tuesday may 7
poster presentation: 17:30-18:30

inpatient hospitalization risk in patients with epilepsy before and after perampanel treatment
poster number: 5-027

poster session: p3
tuesday
 may 7
poster presentation: 17:30-18:30

elevated healthcare burden amongst patients with active generalized tonic-clonic (gtc) convulsions
poster number: 5-004

poster session: p5
thursday
may 9
poster presentation: 17:30-18:30

adjunctive perampanel in pediatric patients with epilepsy: population pharmacokinetic (pk) and exposure-response analyses
poster number: 5-008

poster session: p5
thurs
daymay 9
poster presentation: 17:30-18:30

perampanel in real-world clinical care of patients with epilepsy: retrospective phase iv study 506 – second interim analysis
poster number: 5-009

poster session: p5
thurs
daymay 9
poster presentation: 17:30-18:30

study 506 – second interim analysis of a retrospective, phase iv study of perampanel in real-world clinical care of patients with epilepsy: pediatric subgroup (aged <12 years)
poster number: 5-014

poster session: p5
thursday
may 9
poster presentation: 17:30-18:30

inpatient hospitalization risk in medicaid patients with epilepsy before and after perampanel treatment
poster number: 5-017

poster session: p5
thursd
aymay 9
poster presentation: 17:30-18:30

study 506 – second interim analysis of a retrospective, phase iv study of perampanel in real-world clinical care of patients with epilepsy: adolescent subgroup (aged 12 to <18 years)

 

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 in-house scientists, that inhibits orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptor 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. 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 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 associated with seizures 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 in the united states.

perampanel is currently approved in more than 55 countries and territories, 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”) announced today that in the 8th meeting of the data safety monitoring board (dsmb) for the global phase iii clinical studies (mission ad) on the investigational oral bace (beta amyloid cleaving enzyme) inhibitor elenbecestat (development code: e2609) in early alzheimer’s disease (ad), the dsmb reviewed safety data including the potential for decline in cognition, and recommended the continuation of the studies. elenbecestat is being jointly developed by eisai and biogen inc. (headquarters: cambridge, massachusetts, united states).

the phase iii clinical trial program for elenbecestat (mission ad) consists of two global phase iii clinical studies with identical protocols, mission ad1 (study 301) and mission ad2 (study 302). both studies are multicenter, placebo-controlled, double-blind, parallel-group phase iii clinical studies aiming to assess the efficacy and safety of elenbecestat for treatment in patients with mild cognitive impairment (mci) due to ad or mild ad dementia (collectively known as early ad) with confirmed amyloid pathology in the brain. patients are allocated randomly to receive either 50 mg of elenbecestat or placebo daily during the treatment period of 24 months, and the primary endpoint utilizes the clinical dementia rating sum of boxes (cdr-sb).
enrollment in mission ad is scheduled to be completed in march 2019.

eisai aims to create innovative medicines for alzheimer’s disease as soon as possible in order to further contribute to addressing the unmet medical needs of, as well as potentially increasing the benefits provided to, patients and their families.

 

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 mission ad
initiated in october 2016, the phase iii clinical trial program for elenbecestat (mission ad) consists of two global phase iii clinical studies with identical protocols, mission ad1 (study 301) and mission ad2 (study 302), and is being conducted at over 400 sites in 30 countries worldwide. both studies are multicenter, placebo-controlled, double-blind, parallel-group phase iii clinical studies aiming to assess the efficacy and safety of elenbecestat for treatment in patients with mild cognitive impairment (mci) due to ad or mild ad dementia (collectively known as early ad) with confirmed amyloid pathology in the brain. patients are allocated randomly to receive either 50 mg of elenbecestat or placebo daily during the treatment period of 24 months, and the primary endpoint utilizes the clinical dementia rating sum of boxes (cdr-sb).

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced that a global phase iii clinical study (clarity ad/study 301) of ban2401, an anti-amyloid beta protofibril antibody, in patients with early alzheimer’s disease has been initiated. ban2401 is being jointly developed by eisai and biogen inc. (headquarters: cambridge, massachusetts, united states, “biogen”).

clarity ad is a global placebo-controlled, double-blind, parallel-group, randomized study in 1,566 patients with mild cognitive impairment (mci) due to alzheimer’s disease (ad) or mild alzheimer’s disease dementia (collectively known as early ad) with confirmed amyloid pathology in the brain. after discussion with regulatory agencies based on the results of a phase ii clinical study (study 201), a single phase iii clinical study is being initiated to support a filing for ban2401. the treatment group will be administered a dosage of 10 mg/kg bi-weekly of ban2401, with patients allocated in a 1:1 ratio to receive either placebo or the treatment group. the primary endpoint is the change from baseline in the clinical dementia rating–sum of boxes (cdr-sb) at 18 months of treatment. respective changes from baseline to 18 months of treatment in the ad composite score (adcoms), ad assessment scale–cognitive subscale (adas-cog), and brain amyloid levels as measured by amyloid positron emission tomography (pet) have been set as key secondary endpoints.

eisai aims to create innovative medicines for alzheimer’s disease as soon as possible in order to further contribute to addressing the unmet medical needs of, as well as potentially increasing the benefits provided to, patients and their families.

 

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

 

[notes to editors]
1. about ban2401
ban2401 is a humanized monoclonal antibody for alzheimer’s disease that is the result of a strategic research alliance between eisai and bioarctic. ban2401 selectively binds to neutralize and eliminate soluble, toxic aβ aggregates (protofibril) that are thought to contribute to the neurodegenerative process in alzheimer’s disease. as such, ban2401 may have the potential to have an effect on disease pathology and to slow down the progression of the disease. eisai obtained the global rights to study, develop, manufacture and market ban2401 for the treatment of alzheimer’s disease pursuant to an agreement concluded with bioarctic in december 2007. in march 2014 eisai and biogen entered into a joint development and commercialization agreement for ban2401 and the parties amended that agreement in october 2017.

2. about study 201
study 201 is a placebo-controlled, double-blind, parallel-group, randomized phase ii clinical study in 856 patients with mild cognitive impairment (mci) due to alzheimer’s disease or mild alzheimer’s dementia (collectively known as early alzheimer’s disease) with confirmed amyloid pathology in the brain. this study used bayesian adaptive randomization design to automatically allocate newly enrolled patients into the study to treatment arms showing higher probability of efficacy based on the results of interim analyses. the study design included five dose regimens and placebo, and considered the efficacy of ban2401 as well as dose responsiveness through 16 interim analyses that assessed potential for early success, an analysis based on adcoms at 12 months, and a comprehensive final analysis at 18 months (secondary endpoints). patients who received treatment with ban2401 were randomized to five dose regimens, 2.5 mg/kg biweekly (52 patients), 5 mg/kg monthly (51 patients), 5 mg/kg biweekly (92 patients), 10 mg/kg monthly (253 patients), or 10 mg/kg biweekly (161 patients). biomarker endpoints included changes in aβ accumulated in the brain as measured by amyloid pet (positron emission tomography) as well as in cerebrospinal fluid (csf), while adcoms (alzheimer’s disease composite score), clinical dementia rating sum of boxes (cdr-sb) and alzheimer’s disease assessment scale-cognitive subscale (adas-cog) were measured as efficacy endpoints (clinical).

detailed results of study 201 were presented at alzheimer’s association international conference 2018 and clinical trials on alzheimer’s disease 2018 in july 2018 and october 2018, respectively.

currently, an open-label extension phase of study 201 is ongoing. eligible patients are those enrolled in study 201, and receive the highest dose of ban2401 (10 mg/kg biweekly).

3. about bioarctic ab
bioarctic ab (publ) is a swedish research-based biopharma company focusing on disease modifying treatments and reliable biomarkers and diagnostics for neurodegenerative diseases, such as alzheimer’s disease and parkinson’s disease. the company also develops a potential treatment for complete spinal cord injury. bioarctic focuses on innovative treatments in areas with high unmet medical needs. the company was founded in 2003 based on innovative research from uppsala university, sweden. collaborations with universities are of great importance to the company together with our strategically important global partners in the alzheimer (eisai) and parkinson (abbvie) projects. the project portfolio is a combination of fully funded projects run in partnership with global pharmaceutical companies and innovative in-house projects with significant market- and out-licensing potential. bioarctic’s b-share is listed on nasdaq stockholm mid cap (sto:bioa b). www.bioarctic.com.

tokyo and stamford, conn. – march 12, 2019 – eisai co., ltd. (ceo: haruo naito, “eisai”) and imbrium therapeutics l.p. (imbrium therapeutics), a clinical-stage biopharmaceutical company and operating subsidiary of purdue pharma, l.p. (president and ceo: craig landau, md) today announced that the u.s. food and drug administration (fda) has accepted for review the new drug application (nda) for lemborexant, an investigational agent being studied for the treatment of insomnia, a sleep-wake disorder. a prescription drug user fee act (pdufa) date is set for december 27, 2019.

the nda submission was based on data from the clinical development program including two pivotal phase 3 studies of lemborexant – sunrise 1 (study 304) and sunrise 2 (study 303).

  • sunrise 1: a one-month phase 3 clinical study to evaluate the efficacy and safety of lemborexant versus placebo and versus an active comparator (zolpidem tartrate extended release, “zolpidem er”) in 1,006 patients 55 years and older (45 percent of all patients were aged 65 years and older) with insomnia disorder. this study assessed sleep latency (using latency to persistent sleep; primary objective); sleep efficiency and wake after sleep onset (effect on maintaining sleep; key secondary objectives) objectively using polysomnography, and achieved its primary and key secondary objectives. the most common adverse events (aes) reported in the lemborexant arms were headache and somnolence.1
  • sunrise 2: a 12-month placebo-controlled (first six months) phase 3 clinical study to evaluate the long-term efficacy and safety of lemborexant in 949 adult patients (18 to 88 years of age) with insomnia disorder. this study evaluated subjective (patient-reported) sleep onset latency (primary objective), sleep efficiency, and wake after sleep onset (key secondary objectives) using sleep diaries, and achieved its pre-specified primary and key secondary efficacy objectives. the most common aes reported in the lemborexant arms were somnolence, nasopharyngitis, headache, and influenza.2

“our ultimate goal for the development of a sleep-wake treatment is to bring to patients living with insomnia a new option that has the potential to improve their ability to fall asleep, stay asleep and wake the next morning without impairment,” said lynn kramer, md, chief clinical officer and chief medical officer, neurology business group, eisai. “this milestone for lemborexant brings us one step closer to addressing unmet needs for millions of patients who experience insomnia.”

“insomnia, a disorder of sleep quality and quantity, causes significant impairment in daily functioning and has long-term consequences for health and well-being,”3 said john renger, phd, vice president, head of research & development and regulatory affairs, imbrium therapeutics. “we are committed to working with our partner eisai to make this investigational treatment available to patients, pending regulatory approval.”

lemborexant is being jointly developed by eisai and imbrium therapeutics for the treatment of multiple sleep-wake disorders, including insomnia disorder. information about ongoing clinical studies is available at clinicaltrials.gov.

eisai and imbrium therapeutics are striving to address new unmet medical needs and to improve the lives of patients and their families.

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

 

contacts:
eisai co., ltd.                                                     imbrium therapeutics l.p.
public relations department                              
81-(0)3-3817-5120

 


1. about lemborexant
lemborexant is a novel investigational small molecule compound, discovered and developed by eisai in-house scientists, that inhibits orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptor 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 and imbrium therapeutics are 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 sunrise 1 (study 304)1
sunrise 1 was a multicenter, randomized, double-blind, placebo-controlled, active comparator, parallel-group study evaluating the efficacy and safety of lemborexant in 1,006 male or female adult patients 55 years and older (45 percent of patients were 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 minimum two-week period without treatment prior to the end-of-study visit. in this study, patients were randomized to receive 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 objectives included change from baseline in sleep efficiency and 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, each after the last two nights of one month of treatment.

3. about sunrise 2 (study 303)2
sunrise 2 was a 12-month multicenter, global, randomized, controlled, double-blind, parallel-group study of the efficacy and safety of lemborexant in 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 active-only treatment and a two-week period without treatment prior to the end-of-study visit. in this study, during the placebo-controlled treatment period, patients were randomized to receive placebo or one of two treatment regimens (lemborexant 5 mg or 10 mg). during the active-only treatment period, patients who received placebo during the first period were re-randomized to receive lemborexant 5 mg or 10 mg. patients who received active treatment during the first period continued on the treatment to which they were originally randomized.

the primary objective was change from baseline in subjective sleep onset latency after six months of placebo-controlled treatment using patient reported (subjective) sleep diaries. key secondary endpoints were change from baseline in subjective sleep efficiency and subjective wake after sleep onset (swaso) by using patient reported (subjective) sleep diaries for both lemborexant doses after six months of placebo-controlled treatment.

4. about sleep disorders
population studies show that sleep disorders affect many more people worldwide than previously thought.4 insomnia disorder is the most common sleep disorder affecting approximately 30 percent of the adult population worldwide.4,5 insomnia disorder is characterized by difficulty falling asleep, staying asleep or both, despite an adequate opportunity to sleep, which can lead to daytime consequences such as fatigue, difficulty concentrating and irritability.3,6

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 and dementia, as well as adverse effects on mood and behavior.3,7

experimental studies in animals and humans provide evidence of associations between sleep and disease risk factors, diseases and mortality.8 studies suggest an optimal sleep duration between seven and eight hours.9

women are 1.4 times more likely than men to suffer from insomnia.10 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.11

5. about eisai co., ltd
eisai co., ltd. is a leading global research and development-based pharmaceutical company headquartered in japan. we define our corporate mission as “giving first thought to patients and their families and to increasing the benefits health care provides,” which we call our human health care (hhc) philosophy. with over 10,000 employees working across our global network of r&d facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products in various therapeutic areas with high unmet medical needs, including neurology and oncology. furthermore, we invest and participate in several partnership-based initiatives to improve access to medicines in developing and emerging countries. for more information about eisai co., ltd., please visit .

6. about imbrium therapeutics
imbrium is a clinical-stage biopharmaceutical company dedicated to advancing medical science through the development of important new pharmacologic and biologic therapeutics. we are pursuing treatments for disorders of the central nervous system, oncology chemotherapeutics, and non-opioid approaches to the management of pain. as an operating subsidiary of purdue pharma l.p., imbrium strives to develop and bring to market new medicines that serve the unmet needs of patients, physicians, and health systems worldwide. we have built a robust and diversified pipeline of investigational drug candidates, and we actively collaborate with industry and academic partners to identify and advance future impactful medicines. for more information, please visit .

 

references
1 eisai inc. a multicenter, randomized, double-blind, placebo-conrolled, 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.
2 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.
3 institute of medicine. sleep disorders and sleep deprivation: an unmet public health problem. washington, dc: national academies press. 2006.
4 ferrie je, et al. sleep epidemiology – a rapidly growing field. int j epidemiol. 2011;40(6):1431–1437.
5 roth t. insomnia: definition, prevalence, etiology and consequences. j clin sleep med. 2007;3(5 suppl):s7–s10.
6 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.
7 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.
8 cappuccio fp et al. sleep and cardio-metabolic disease. curr cardiol rep. 2017;19:110.
9 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.
10 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.
11 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 it has submitted an application to the european medicines agency (ema) for its in-house discovered antiepileptic drug (aed) fycompa® (perampanel) seeking approval for use in pediatric patients with epilepsy.

this application aims to expand the indication for fycompa, which is already approved for adjunctive use in patients aged 12 years and older with partial-onset seizures (with or without secondarily generalized seizures) or primarily generalized tonic-clonic seizures, to cover pediatric patients as well.

this application was based on the results of phase iii (study 311) and phase ii (study 232) clinical studies conducted globally to evaluate fycompa as adjunctive therapy in pediatric patients. study 311 evaluated the safety, tolerability, as well as relationship between efficacy and blood concentration of fycompa when administered as an adjunctive therapy in pediatric patients (age 4 to less than 12 years) with inadequately controlled partial-onset seizures or tonic-clonic seizures. study 232 evaluated the pharmacokinetics, efficacy, and long-term safety of adjunctive perampanel in pediatric patients (from 2 to less than 12 years of age). detailed results of both studies will be presented at upcoming academic conferences, respectively.

discovered at eisai’s tsukuba research laboratories, fycompa is a first-in-class aed that is a highly selective, noncompetitive ampa receptor antagonist which reduces neuronal hyperexcitation by targeting glutamate activity at ampa receptors on postsynaptic membranes. available in tablet form to be taken orally once daily, fycompa has been approved in over 55 countries in the world and has been used to treat more than 200,000 patients worldwide to date. regarding the indication covering pediatric patients, fycompa was approved in the united states in september 2018, and an application was submitted in japan in january 2019.

it is estimated that there are approximately 6 million patients with epilepsy in europe, and although onset occurs at any age, onset is most common in people aged 18 and younger and the elderly.

eisai considers neurology including epilepsy, a therapeutic area of focus, and in continued 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.

 

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

 

[notes to editors]
1. about fycompa (perampanel)
fycompa 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 associated with seizures by targeting glutamate activity at ampa receptors on postsynaptic membranes. fycompa is available in tablet form to be taken once daily orally at bedtime. in addition, an oral suspension formulation has been approved in the united states.
fycompa is currently approved in more than 55 countries and territories, 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, fycompa 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, fycompa 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 fycompa 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.
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.

 

2. about study 311

study title: an open-label study to evaluate the safety, tolerability, and exposure-efficacy relationship of fycompa oral suspension when administered as an adjunctive therapy in pediatric subjects (age 4 to less than 12 years) with inadequately controlled partial-onset seizures or primary generalized tonic clonic seizures
study population: 180 patients aged 4 to 12 with inadequately controlled partial-onset seizures or primarily generalized tonic-clonic seizures
treatment administered: 2 – 16 mg of fycompa administered orally once daily before bedtime
duration of treatment: treatment phase (titration period: up to 11 weeks, maintenance period: up to 12 weeks)

extension phase

study locations: global (united states, europe, japan, asia)
primary endpoint: safety and tolerability
results: in the 180 patients who were administered fycompa, efficacy was similar to that observed in patients 12 years of age and older. the most common adverse events (incidence of 10% or higher) observed in this study were somnolence, nasopharyngitis, pyrexia, vomiting, dizziness, influenza, and irritability, which is consistent with the safety profile of fycompa to date.

 

3. about study 232
study 232 was a global (united states, europe), multicenter, open-label clinical study with an extension phase to evaluate 63 pediatric patients with epilepsy (ages 2 to less than 12). the study evaluated the pharmacokinetics, safety, tolerability and efficacy of fycompa oral suspension taken at the same time as other aeds. administration of once-daily fycompa was titrated from 0.015 mg/kg to 0.18 mg/kg, and long-term safety was confirmed after 11 weeks of treatment and an extension phase (41 weeks). the adverse events (≥10% in the fycompa arms) observed in study 232 were pyrexia, fatigue, vomiting, irritability, somnolence, dizziness, upper respiratory tract infection.


4. about epilepsy
it has been reported that epilepsy affects approximately 3.4 million people in the united states, 1 million people in japan, 6 million people in europe, 9 million people in china, and approximately 60 million people worldwide. as approximately 30% of patients with epilepsy are unable to control their seizures with currently available aeds,1 this is a disease with significant unmet medical need.
epilepsy is broadly categorized by seizure type, with partial-onset seizures accounting for approximately 60% of epilepsy cases and generalized seizures accounting for approximately 40%. in a partial-onset seizure, an abnormal electrical disturbance occurs in a limited area of the brain, and may subsequently spread throughout the brain, becoming a generalized seizure (known as a secondarily generalized seizure). in a generalized seizure, abnormal electrical disturbances occur throughout the brain, and can be followed by a loss of consciousness or physical symptoms manifested throughout the whole body.

 

1 “the epilepsies and seizures: hope through research. what are the epilepsies?” national institute of neurological disorders and stroke, accessed may 24, 2016, 

six-month data show significant improvements in patient-reported measures of sleep onset and sleep maintenance for investigational agent lemborexant

tokyo and stamford, conn. – february 4, 2019 – eisai co., ltd. (ceo: haruo naito, “eisai”) and purdue pharma l.p. (president and ceo: craig landau, md, “purdue pharma”) today announced six-month results from sunrise 2, a long-term phase 3 clinical study evaluating the efficacy and safety of lemborexant, an investigational agent being developed for the treatment of insomnia, a sleep-wake disorder. data were presented at the sleep research society’s advances in sleep and circadian science conference, taking place in clearwater beach, florida, feb. 1-4, 2019.

sunrise 2 was a 12-month multicenter, global, randomized, controlled, double-blind, parallel-group study of the efficacy and safety of lemborexant in 949 adult patients (18 to 88 years of age) with insomnia disorder, which was characterized by difficulty falling asleep and/or staying asleep. approximately 28 percent of the patients randomized and treated were 65 years of age or older. during the first six months of the study, patients were randomized to receive either lemborexant 5 mg, lemborexant 10 mg, or placebo. the primary and key secondary efficacy objectives were assessed by patient self-reports via electronic sleep diaries.

at the end of the six-month, placebo-controlled treatment period, treatment with lemborexant at either 5 mg or 10 mg resulted in statistically significant improvements compared to placebo in patient-reported (subjective) sleep onset latency (ssol), the study’s primary efficacy endpoint, and subjective sleep efficiency (sse) and subjective wake after sleep onset (swaso), the study’s key secondary endpoints. six-month results from the study showed that:
● median reductions from baseline in ssol with lemborexant 5 mg (21.81 minutes) and 10 mg (28.21 minutes) were larger and statistically significant compared to placebo (11.43 minutes) at the end of month six (p<0.0001 for all treatment groups).
● improvements from baseline, as measured by least squares mean (lsm), in sse with lemborexant 5 mg (14.19 percent, p=0.0001) and 10 mg (14.31 percent, p<0.0001) were larger and statistically significant compared to placebo (9.64 percent) at the end of month six.
● reductions from baseline in swaso, as measured by lsm, with lemborexant 5 mg (46.75 minutes, p=0.0005) and 10 mg (41.95 minutes, p=0.0105) were larger and statistically significant compared with placebo (29.28 minutes) at the end of month six.

most adverse events (aes) reported were mild to moderate. serious aes were reported at a rate of 2.2 percent (lemborexant 5 mg), and 2.9 percent (lemborexant 10 mg), and 1.6 percent (placebo); only one was considered treatment-related. the most common aes reported, greater than 5 percent in either lemborexant treatment arm and greater than placebo, were somnolence, headache, and influenza. discontinuation rates due to aes were comparable between placebo and lemborexant 5 mg (3.8 percent and 4.1 percent, respectively), and higher for lemborexant 10 mg (8.3 percent).

“these findings add to the growing body of clinical data supporting the development of lemborexant for the treatment of insomnia, and we look forward to presenting 12-month results from the study in a future scientific forum,” said lynn kramer, md, chief clinical officer and chief medical officer, neurology business group, eisai. “it remains our aspiration to bring a medicine to physicians and patients that helps patients sleep well at night and wake well in the morning.”

sunrise 2 is one of two phase 3 safety and efficacy studies of lemborexant conducted by eisai and purdue pharma. these studies supported the new drug application for lemborexant for the treatment of insomnia, filed with the u.s. food and drug administration, on december 27, 2018. in japan, an application is scheduled to be filed within fiscal 2018.

“the six-month findings from sunrise 2 are exciting, highlighting improvements in subjective measures of both sleep onset and sleep maintenance,” said john renger, phd, head of research & development and regulatory affairs, purdue pharma. “sunrise 2 was a robust phase 3 clinical study in which the self-reported patient outcomes are encouraging as they reflect the patients’ perception of lemborexant’s impact on enabling the patient to both fall asleep faster and stay asleep longer.”

lemborexant, which acts on the orexin neurotransmitter system and is believed to regulate sleep and wake by dampening wakefulness without impeding the ability to awaken to external stimuli, is being jointly developed by eisai and purdue pharma for the treatment of multiple sleep-wake disorders, including insomnia disorder. in addition to the treatment of insomnia disorder, a phase 2 clinical study of lemborexant in patients with irregular sleep-wake rhythm disorder and mild to moderate alzheimer’s dementia is underway. information about ongoing clinical studies is available at clinicaltrials.gov.

eisai and purdue pharma are striving to address new unmet medical needs and to improve the lives of patients and their families.

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

contacts:
eisai co., ltd.
                                    purdue pharma l.p.
public relations department               danielle lewis
81-(0)3-3817-5120                            1-203-588-7653

 
1. about lemborexant

lemborexant is a novel investigational small molecule compound, discovered and developed by eisai in-house scientists, that inhibits orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptor 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 which regulates wakefulness is not functioning normally, suggesting that inhibiting inappropriate orexin signaling may enable initiation and maintenance of sleep.

2. about sunrise 21
sunrise 2 was a 12-month multicenter, global, randomized, controlled, double-blind, parallel-group study of the efficacy and safety of lemborexant in 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 active-only treatment and a two-week period without treatment prior to the end-of-study visit. in this study, during the placebo-controlled treatment period, patients were randomized to receive placebo or one of two treatment regimens (lemborexant 5 mg or 10 mg). during the active-only treatment period, patients who received placebo during the first period were re-randomized to receive lemborexant 5 mg or 10 mg. patients who received active treatment during the first period continued on the treatment to which they were originally randomized. the primary objective was to determine the efficacy of lemborexant 5 mg and 10 mg compared to placebo on patient-reported (subjective) sleep onset latency at the end of six months of treatment. key secondary endpoints were mean change from baseline in subjective sleep efficiency and subjective wake after sleep onset (swaso) for lemborexant 5 mg and 10 mg compared to placebo at the end of six months of treatment.

3. about sleep disorders
population studies show that sleep disorders affect many more people worldwide than previously thought.insomnia disorder is the most common sleep disorder affecting approximately 30 percent of the adult population worldwide.2,3 insomnia disorder is characterized by difficulty falling asleep, staying asleep or both, despite an adequate opportunity to sleep, which can lead to daytime consequences such as fatigue, difficulty concentrating and irritability.4,5
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 and dementia, as well as adverse effects on mood and behavior.4,6
experimental studies in animals and humans provide evidence of associations between sleep and disease risk factors, diseases and mortality.7 studies suggest an optimal sleep duration between seven and eight hours.8
women are 1.4 times more likely than men to suffer from insomnia.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.10 

4. about eisai co., ltd
eisai co., ltd. is a leading global research and development-based pharmaceutical company headquartered in japan. we define our corporate mission as “giving first thought to patients and their families and to increasing the benefits health care provides,” which we call our human health care (hhc) philosophy. with approximately 10,000 employees working across our global network of r&d facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products in various therapeutic areas with high unmet medical needs, including neurology and oncology.
furthermore, we invest and participate in several partnership-based initiatives to improve access to medicines in developing and emerging countries.
for more information about eisai co., ltd., please visit  

5. about purdue pharma l.p.
purdue pharma l.p. develops and provides prescription medicines that meet the evolving needs of healthcare professionals, patients, and caregivers. we were founded by physicians and we are currently led by a physician. beyond our efforts to provide quality medications, purdue pharma is committed to supporting national, regional and local collaborations to drive innovations in patient care. privately held, purdue pharma is pursuing a pipeline of new medications and technologies through internal research & development and strategic industry partnerships. for more information, please visit .

references 
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.
2 ferrie je, et al. sleep epidemiology – a rapidly growing field. int j epidemiol.2011;40(6):1431–1437.
3 roth t. insomnia: definition, prevalence, etiology and consequences. j clin sleep med. 2007;3(5 suppl):s7–s10.
institute of medicine. sleep disorders and sleep deprivation: an unmet public health problem. washington, dc: national academies press. 2006.
5 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.
6 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.
7 cappuccio fp et al. sleep and cardio-metabolic disease. curr cardiol rep. 2017;19:110.
8 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.
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.
10 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 it has filed a supplementary new drug application in japan for its in-house discovered antiepileptic drug (aed) fycompa® (perampanel) seeking approval 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 new fine granule formulation.

the submission covering monotherapy for partial-onset seizures was based on the results of a phase iii clinical study (freedom/study 342) conducted in japan and south korea. in freedom, the percentage of untreated patients from 12 to 74 years of age with partial onset seizures who achieved seizure freedom with fycompa monotherapy exceeded the criteria for efficacy*, and the primary endpoint was met. the most common adverse events (incidence of 10% or higher) observed in this study were dizziness, somnolence, nasopharyngitis and headache, which is consistent with the safety profile of fycompa to date.

the submission covering partial-onset seizures in pediatric patients was based on the results of a phase iii clinical study (study 311) of fycompa as adjunctive therapy in pediatric patients conducted in japan, the united states and europe. in study 311 which evaluated fycompa in pediatric patients (ages 4 to less than 12 years) with inadequately controlled partial-onset seizures or primary generalized tonic-clonic seizures, it was demonstrated that the safety and efficacy of fycompa in pediatric patients was similar to that observed in patients 12 years of age and older.

in addition, regarding the additional application for the fine granule formulation, eisai developed this formulation to make it easier to administer fycompa to children and patients who have difficulty taking tablets, and subsequently conducted a clinical study verifying bioequivalence with the tablet formulation, which led to this application.

detailed results of freedom and study 311 will be presented at upcoming academic conferences.

discovered at eisai’s tsukuba research laboratories, fycompa is a first-in-class aed that is a highly selective, noncompetitive ampa receptor antagonist which reduces neuronal hyperexcitation by targeting glutamate activity at ampa receptors on postsynaptic membranes. available in tablet form to be taken orally once daily, fycompa is approved in japan as an adjunctive therapy for partial-onset seizures (including secondarily generalized seizures) or primary generalized tonic-clonic seizures in patients with epilepsy showing inadequate response to other aeds.

it is estimated that there are approximately 1 million patients with epilepsy in japan, and although onset occurs at any age, onset is most common in people aged 18 and younger and the elderly.

eisai considers neurology including epilepsy, a therapeutic area of focus, and in continued 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.

 

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

 

[notes to editors]
1. about fycompa (perampanel)
fycompa 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 associated with seizures by targeting glutamate activity at ampa receptors on postsynaptic membranes. fycompa is available in tablet form to be taken once daily orally at bedtime. in addition, an oral suspension formulation has been approved in the united states.

fycompa is currently approved in more than 55 countries and territories, 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, fycompa 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 primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older. in the united states, fycompa 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.

to date, fycompa has been used to treat more than 200,000 patients worldwide across all indications.

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

 

2. about study 342 (freedom)

study title: an uncontrolled, open-label study for verification of efficacy and safety for perampanel monotherapy in untreated patients with partial onset seizures (including secondarily generalized seizures)
study population: 89 untreated patients aged 12 to 74 with partial-onset seizures with or without secondarily generalized seizures
treatment administered: up to 4 mg of perampanel administered orally once daily before bedtime (may be titrated up to 8 mg if seizures occur)
duration of treatment: treatment phase (titration period: 6 weeks, maintenance period: 26 weeks (if titrated up from 4 mg to 8 mg, titration period is 4 weeks and treatment period is 26 weeks))

extension phase

study locations: japan, south korea
primary endpoint: seizure-free rate during 26-week maintenance period for participants with partial onset seizures
results: 89 patients were administered fycompa as monotherapy, and the proportion of 73 patients for evaluation receiving 4 mg who were seizure-free during the treatment period exceeded the efficacy criteria*, and the primary endpoint was met. in addition, the interim results demonstrated that the 4 mg and 8 mg patients combined also exceeded the efficacy criteria. the most common adverse events (incidence of 10% or higher) observed in this study were dizziness, somnolence, nasopharyngitis and headache, which is consistent with the safety profile of fycompa to date

*the criteria for efficacy in this study with 73 patients for evaluation of efficacy required a 52.1% or higher proportion of patients to have achieved seizure freedom, which was set primarily in consideration of the results from other aed monotherapy studies.


3. about study 311

study title: an open-label study to evaluate the safety, tolerability, and exposure-efficacy relationship of perampanel oral suspension when administered as an adjunctive therapy in pediatric subjects with inadequately controlled partial-onset seizures or primary generalized tonic clonic seizures
study population: 180 patients aged 4 to 12 with inadequately controlled partial-onset seizures or primarily generalized tonic-clonic seizures.
treatment administered: 2 – 16 mg of perampanel administered orally once daily before bedtime
duration of treatment: treatment phase (titration period: up to 11 weeks, maintenance period: up to 12 weeks)

extension phase

study locations: global (united states, europe, japan, asia)
primary endpoint: safety and tolerability
results: in the 180 patients who were administered fycompa, efficacy was similar to that observed in patients 12 years of age and older. the most common adverse events (incidence of 10% or higher) observed in this study were somnolence, nasopharyngitis, pyrexia, vomiting, dizziness, influenza, and irritability, which is consistent with the safety profile of fycompa to date.


4. about epilepsy

epilepsy affects approximately 3.4 million people in the united states, 1 million people in japan, 6 million people in europe, 9 million people in china, and approximately 60 million people worldwide. as approximately 30% of patients with epilepsy are unable to control their seizures with currently available aeds,1 this is a disease with significant unmet medical need.

epilepsy is broadly categorized by seizure type, with partial-onset seizures accounting for approximately 60% of epilepsy cases and generalized seizures accounting for approximately 40%. in a partial-onset seizure, an abnormal electrical disturbance occurs in a limited area of the brain, and may subsequently spread throughout the brain, becoming a generalized seizure (known as a secondarily generalized seizure). in a generalized seizure, abnormal electrical disturbances occur throughout the brain, and can be followed by a loss of consciousness or physical symptoms manifested throughout the whole body.

 

1 “the epilepsies and seizures: hope through research. what are the epilepsies?” national institute of neurological disorders and stroke, accessed may 24, 2016, 

网站地图