news – page 14 – eisai china lnc.-pg电子app

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that it has launched a new fine granule formulation of its in-house-discovered antiepileptic drug (aed) fycompa^® (perampanel hydrate) in japan on july 6, 2020. eisai received marketing and manufacturing approval for this formulation on january 23, 2020, and the fine granule formulation was added to japan’s national health insurance drug price list on april 23 of the same year.

in japan, it is estimated that there are approximately 1 million patients with epilepsy. while epilepsy is a disease that may occur regardless of age, it is said that incidence is particularly high in children and the elderly. this newly launched fine granule formula was developed so that even patients who have difficulty taking tablets such as children or those who have difficulties in taking tablets due to reduced swallowing ability may take this drug. additionally, greater ability to adjust dosage to match patients’ symptoms becomes possible.

fycompa is a first-in-class aed discovered at eisai’s tsukuba research laboratories and was developed in-house. it is a highly selective, noncompetitive ampa receptor antagonist that reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity at postsynaptic ampa receptors. in japan, fycompa is currently 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, as well as adjunctive treatment for primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older.

with the launch of this fine granule formulation in japan, eisai will continue to prioritize the provision of safety information. furthermore, eisai will pursue its mission of delivering “seizure freedom” to as many patients as possible, and seek 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. product information
1) product name
fycompa^® fine granules 1%

2) generic name
perampanel hydrate

3) indications 
    partial-onset seizures (including secondarily generalized seizures)
adjunctive therapy with antiepileptic drugs for tonic-clonic seizures below in patients with epilepsy showing inadequate response to other antiepileptic drugs

4) price 
fycompa fine granules 1%: 1,068.90 yen per 1g containing 1% (package price: 106,890 yen)

5) packaging
bottles of 100 g

6) product image

2. about fycompa (perampanel hydrate)

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 drug form to be taken once daily orally at bedtime. an oral suspension formulation and tablet have been approved in the united states and europe.

fycompa is currently approved in more than 65 countries and territories, including japan, the united states, china, and other countries 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. in addition, fycompa has been approved in more than 60 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 japan and 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 europe, an application has been submitted seeking the additional approval of fycompa 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. to date, fycompa has been used to treat more than 300,000 patients worldwide across all indications.

eisai is conducting a global phase iii clinical study (study 338) for the agent in patients with seizures associated with lennox-gastaut syndrome. in addition, eisai is conducting development of an injection formulation.

 

3. about epilepsy

epilepsy affects approximately 1 million people in japan, 3.4 million people in the united states, 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 aeds¹, 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,  .

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that its u.s. subsidiary eisai inc. has launched its in-house discovered orexin receptor antagonist dayvigo™ (lemborexant) civ for the treatment of adults with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance in the u.s. on june 1, 2020.

discovered at eisai’s tsukuba research laboratories and developed in-house, dayvigo is a small-molecule compound. the mechanism of action in the treatment of insomnia is presumed to be through antagonism of orexin receptors¹. the orexin neuropeptide signaling system plays a role in wakefulness¹. 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 (ic50 values of 6.1 nm and 2.6 nm, respectively).

dayvigo was approved in the u.s. by the u.s. food and drug administration (fda) based on findings from the lemborexant clinical development program, which included two pivotal phase 3 studies² (sunrise 1 and sunrise 2) in nearly 2,000 adult patients with insomnia.

sunrise 1 was a 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 (the diagnostic and statistical manual of mental disorders – 5th edition) criteria for insomnia disorder. 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 secondary efficacy endpoints in sunrise 1 were the mean change from baseline to end of treatment (day 29/30) in sleep efficiency (sef) 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 and active-controlled.

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. 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 sleep onset. pre-specified secondary efficacy endpoints for sleep maintenance were change from baseline to end of treatment at six months for patient reported sleep efficiency (ssef; defined as the proportion of time spent asleep per time in bed) and wake after sleep onset (swaso; defined as the minutes of wake from the onset of sleep until wake time). the pre-specified primary and 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 ssef and swaso.¹

analyses in both studies suggested dayvigo was not associated with rebound insomnia, and there was no evidence of withdrawal effects following treatment discontinuation, suggesting it does not produce physical dependence in those taking it for up to one year. dayvigo is the first fda-approved insomnia medication with safety data over a 12-month treatment period and with sleep onset and sleep maintenance efficacy data over a six-month treatment period in a pivotal clinical study.

the most common adverse reaction (reported in 5% or more of patients treated with dayvigo and at least twice the rate of placebo) in the sunrise1 and sunrise2 (sunrise2 was initiated 30 days after first dosing) studies was somnolence (dayvigo 10 mg, 10%; dayvigo 5 mg, 7%; placebo, 1%).

in a special safety study (study 106)³, dayvigo at 5 mg and 10 mg doses did not cause statistically significant impairment in next morning driving performance in healthy adult or elderly subjects (compared with placebo). impairment was seen in some people taking the 10 mg dose. patients using the 10 mg dose should be cautioned about the potential for next-morning driving impairment because there is individual variation in sensitivity to dayvigo. additional special safety studies (study 108)⁴evaluated middle-of-the-night safety, next morning postural stability and memory. the effects of dayvigo on next day postural stability 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 and placebo on next-day postural stability or memory at either dose. patients should be cautioned about the potential for middle-of-the-night postural instability as well as attention and memory impairment.

dayvigo (5 mg, 10 mg tablets) received approval from the u.s. fda in december 2019, and was designated as a schedule iv controlled substance by the u.s. drug enforcement administration (dea) in april 2020. according to this schedule iv designation, individuals with a history of abuse or addiction to alcohol or other drugs may be at an increased risk for abuse and addiction to dayvigo and such patients should be followed carefully. eisai received manufacturing and marketing approval for dayvigo as an insomnia treatment in japan in january 2020, and was included in japan’s national health insurance drug price list in april 2020. it is being prepared for launch in japan. eisai has also submitted a new drug application seeking approval of this agent for use in the treatment of insomnia in canada in august 2019.

insomnia is characterized by difficulty falling asleep, staying asleep, or both, despite an adequate opportunity to sleep^{5, 6}. 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 persist for months to years.

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

 

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

 

[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 (ic50 values of 6.1 nm and 2.6 nm, respectively) and acts as a competitive antagonist with stronger inhibition effect to ox2r. in individuals with insomnia, it is possible that orexin signaling regulating wakefulness is not functioning normally.

the orexin neuropeptide signaling system plays a role in wakefulness.² blocking the binding of wake-promoting neuropeptides orexin a and orexin b to receptors ox1r and ox2r is thought to suppress wake drive. dayvigo is being prepared for launch in japan. eisai has also submitted a new drug application seeking approval of this agent for use in the treatment of insomnia in canada in august 2019.

for further information on dayvigo in the united states, including important safety information (isi), please visit the dayvigo website ().

2. about sleep-wake disorders and insomnia
sleep-wake disorders consist of disease categories such as insomnia, irregular sleep-wake rhythm disorder (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.^5,6

diagnostic criteria in the u.s. for insomnia disorder include if the sleep disturbance causes clinically significant distress or impairment in social, occupational, educational, academic, behavioral or other important areas of functioning, occurs at least three nights per week and is present for at least three months.

sleeping well is essential for good health⁹, and studies suggest an optimal sleep duration between seven and eight hours.¹⁰ poor sleep is associated with a wide range of health consequences.^5,12

women are 1.4 times more likely than men to suffer from insomnia.¹¹ 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.¹²

3. about sunrise 1 (study 304)²
sunrise 1 is a one-month trial in adult female patients age 55 and older and male patients 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 from baseline to end of treatment at days 29/30 in latency to persistent sleep (lps; the number of minutes from lights off to the first 10 consecutive minutes of non-wakefulness). secondary efficacy endpoints were the mean change from baseline to end of treatment at days 29/30 in sleep efficiency (sef) and wake after sleep onset (waso). these endpoints were measured by overnight polysomnography monitoring.

4. about sunrise 2 (study 303)²
sunrise 2 is a six-month placebo-controlled treatment trial with a 6-month parallel-group extension period including 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 subjective sleep onset latency (ssol; the estimated minutes from the time that the patient attempted to sleep until sleep onset). secondary efficacy endpoints were mean change from baseline to end of treatment at six months subjective sleep efficiency (ssef; the proportion of time spent asleep per time in bed) and wake after sleep onset (swaso; the minutes of wake from the onset of sleep until wake time). these endpoints were measured by sleep diary.

5. about study 106³
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 mg 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 108⁴
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 active control. there was a statistically significant increase in body sway for both doses of lemborexant compared with placebo. the next morning, shortly after the end of eight hours in bed neither dose of lemborexant had statistically significant residual effects on this measure of postural stability as compared to placebo.
references
¹ scammell te, winrow cj. orexin receptors: pharmacology and therapeutic opportunities. annu rev pharmacol toxicol. 2011;51:243‐266.
² eisai inc. dayvigo full prescribing information. 2020.
³ vermeeren a, et al. on-the-road driving performance the morning after bedtime administration of lemborexant in healthy adult and elderly volunteers. sleep. 2019 42 (4): zsy260.
⁴ murphy p, et al. safety of lemborexant versus placebo and zolpidem: effects on auditory awakening threshold, postural stability, and cognitive performance in healthy older participants in the middle of the night and upon morning awakening, j. clinical sleep medicine. 2020: 16(5):765-773.
⁵ institute of medicine. sleep disorders and sleep deprivation: an unmet public health problem. washington, dc: national academies press. 2006.
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 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 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 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 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.
¹² 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 regarding its in-house discovered lenvatinib mesylate (multikinase inhibitor, product name: lenvima^®, “lenvatinib”) and eribulin mesylate (halichondrin class microtubule dynamics inhibitor, product name: halaven^®, “eribulin”) will be given at the american society of clinical oncology (asco20 virtual scientific program*), from may 29 to 31, 2020.
* presentation materials will be made available on demand via asco’s website at 8:00 am on may 29^th (et).

at this year’s meeting, the final results of two studies will be presented on the combination therapy of lenvatinib with the anti-pd-1 antibody keytruda^® (generic name: pembrolizumab, “pembrolizumab”) from merck & co., inc., kenilworth, n.j., u.s.a. (known as msd outside the united states and canada). one is the oral presentation of the metastatic renal cell carcinoma cohort (abstract number: 5008) of study 111 / keynote-146, and the other is the poster discussion presentation of the first-line therapy for unresectable hepatocellular carcinoma (abstract number: 4519) in study 116 / keynote-524**.
**this release discusses investigational compounds and investigational uses for fda-approved products. it is not intended to convey conclusions about efficacy and safety. there is no guarantee that any investigational compounds and investigational uses of fda-approved products will successfully complete clinical development or gain fda approval.

in march 2018, eisai and merck & co., inc., kenilworth, n.j., u.s.a., through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvatinib.

eisai positions oncology as a key franchise area and aims to create innovative drugs that act towards curing cancer. eisai will continue to create innovation in the development of new drugs based on cutting-edge cancer research, and aims to make continuous efforts to meet the diversified needs of and increase the benefits provided to patients with cancer, their families, and healthcare professionals.

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) and seikagaku corporation (headquarters: tokyo, president: ken mizutani, “seikagaku”) announced today that the companies have entered into an agreement for the co-development and marketing alliance in china for si-613 (diclofenac conjugated sodium hyaluronate), a therapeutic agent for osteoarthritis discovered by seikagaku.

on the basis of this agreement, the companies will jointly develop si-613 in china for a treatment of knee osteoarthritis. after obtaining approval, seikagaku will supply products to eisai, and eisai will be responsible for distribution. the companies will cover an equal share of the development cost, and eisai will pay seikagaku the upfront payment, and development as well as sales milestones.

osteoarthritis is a disease caused by the articular cartilage damage due to aging and other factors, leading to inflammation and pain, which result in impaired quality of life (qol). knee osteoarthritis is one of the most frequent cases among thereof, and the number of symptomatic patients with knee osteoarthritis in china is estimated to be approximately 47 million*1, and it is anticipated that the number will continue to increase as the population ages.

si-613 is diclofenac conjugated sodium hyaluronate created by seikagaku using their proprietary drug-binding technology to chemically bond hyaluronic acid and diclofenac (an anti-inflammatory drug). this material has the analgesic and anti-inflammatory effects of diclofenac, which is designed to be sustained-released*2 by a drug delivery system*3, in addition to the joint function improving effect of sodium hyaluronate. hence, it is expected that si-613 rapidly and continuously reduces the pain and inflammation associated with osteoarthritis.

under this agreement, eisai aims to contribute to patients with knee osteoarthritis that is unmet medical needs by utilizing the knowledge and networks that eisai has cultivated through its china business. seikagaku will seek to maximize the value of si-613 in china by leveraging eisai’s business base in china.
through the development and commercialization of si-613, the companies will provide new treatment options in china for knee osteoarthritis and contribute to improving the qol of patients.

references:
*1: for the estimated data regarding the number of patients with knee osteoarthritis
 · data of morbidity prevalence rate – the prevalence of symptomatic knee osteoarthritis in china, arthritis & rheumatology(2016)
· estimated data calculated from united nations world population estimates – world population prospects, url：http://www.un.org/en/development/desa/population/
*2: sustained release is a gradual release of the active pharmaceutical ingredients of a drug to achieve a sustained therapeutic effect.
*3: drug delivery system (dds) is a technology for the controlled release, targeting, and absorption improvement of drugs.

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that it has submitted in japan a marketing authorization application of the anticancer agent denileukin diftitox (genetic recombinant) (generic name, development code: e7777) for relapsed or refractory cutaneous t-cell lymphoma (ctcl) and peripheral t-cell lymphoma (ptcl).

this application is based on data from a multicenter, open-label, single-arm phase ii clinical study (study 205) conducted in japan for patients with relapsed or refractory ctcl or ptcl to evaluate the efficacy and safety of this agent.

this study achieved the primary endpoint and exceeded a predetermined threshold with statistical significance: the objective response rate (orr) of ctcl and ptcl patients in total (n=36) was 36.1% (95% confidence interval (ci): 20.8-53.8). the orrs of each subtype were 31.6% (95% ci：12.6-56.6) for ctcl (n=19) and 41.2% (95%ci: 18.4-67.1) for ptcl (n=17).

the five most frequent adverse events observed in this study were increased aspartate aminotransferase (ast) (89.2%), increased alanine aminotransferase (alt) (86.5%), hypoalbuminaemia (70.3%), lymphopenia (70.3%), and pyrexia (51.4%).

denileukin diftitox (genetic recombinant) is a fusion protein of the receptor-binding portion of interleukin-2 (il-2) and diphtheria toxin that specifically binds to the il-2 receptor on the surface of tumoral lymphocyte. the antitumor effect of denileukin diftitox depends on the intracellular delivery of diphtheria toxin which inhibits protein synthesis and induces cell death. the agent has been evaluated as a drug with high medical need by the “study group for unapproved drugs/off-label drugs for high medical needs”*, and eisai has been requested to develop it by the ministry of health, labour and welfare.

eisai positions oncology as a key franchise area and aims to create innovative drugs that act towards curing cancer. eisai aims to make continuous efforts to meet the diversified needs of and increase the benefits provided to patients with cancer, their families, and healthcare professionals.