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news – page 12 – eisai china lnc.-leyu手机版登录入口app

amgen and eisai to participate in the immune modulation domain of remap-covid, an adaptive clinical trial to test interventions for patients hospitalized with covid-19

amgen’s apremilast and eisai’s eritoran to be evaluated across multiple international trial sites within the remap network

(business wire)–global coalition for adaptive research (los angeles, ca), amgen (thousand oaks, ca), and eisai co., ltd. (tokyo, japan “eisai”) — the global coalition for adaptive research (gcar) in collaboration with amgen and eisai, today announced enrollment of the first patient in the immune modulation domain of remap-covid, a sub-study of remap-cap (a randomized, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia) that tests multiple interventions for the treatment of patients hospitalized with covid-19. amgen’s apremilast and eisai’s investigational eritoran are being evaluated as potential therapeutic agents.

remap-cap was developed to test treatments for severe pneumonia both in non-pandemic and pandemic settings. in february 2020, remap-cap rapidly pivoted to its pandemic mode (the remap-covid sub-study), as per its original intent, to incorporate additional potential treatment regimens specifically targeting covid-19 and to expand enrollment to covid-19 patients. this trial is a multicenter, randomized platform study, with treatments tested within groupings or “domains” based on pathway or mechanism of action.

the trial is being conducted in the multi-hospital upmc (university of pittsburgh medical center) health system along with over 20 hospitals in the united states. additional global sites across the trial network will follow. university of pittsburgh is serving as the u.s. regional coordinating center.

“partnering with the biopharmaceutical industry to be able to efficiently test well-understood targeted agents is critical to understanding treatment paradigms for covid-19 patients,” says derek angus, md., mph, frcp, u.s. principal investigator of remap and chief healthcare innovation officer, upmc health system. “today’s announcement marks an important milestone in the collaboration between industry and the scientific and academic community to work collectively to evaluate potentially promising therapies to support patients hospitalized with covid-19.”

amgen’s apremilast is an oral drug which inhibits the activity of pde4 (phosphodiesterase 4), an enzyme found in inflammatory cells in the human body. by inhibiting pde4, apremilast is thought to modulate the production of inflammatory cytokines and other mediators, which may prove helpful in inhibiting the inflammatory response associated with the signs, symptoms and pulmonary involvements observed in some covid-19 patients. apremilast is currently approved for use in more than 45 countries as an oral treatment for inflammatory diseases including moderate to severe plaque psoriasis, psoriatic arthritis and oral ulcers associated with behcet’s disease.

“amgen believes that, based on its mechanism of action, apremilast might help prevent the respiratory distress seen in moderate to severe-stage adult covid-19 patients,” said david m. reese, m.d., executive vice president of research and development at amgen. “we are proud to be joining remap-covid, which is an important and innovative effort utilizing a platform approach and has the potential to rapidly identify whether apremilast may improve health outcomes for patients hospitalized with moderate to severe covid-19.”

eritoran is eisai’s in-house discovered and developed investigational tlr4 (toll-like receptor 4) antagonist created with natural product organic synthesis technology. it is a structural analogue of lipid a, which is an activator of endotoxins of bacteria. it has been previously observed to be safe in 14 clinical studies including a large phase 3 randomized trial in severe sepsis. it is expected to suppress inflammation and increasing in severity caused by covid-19 by inhibiting the activation of tlr4, which is found in the most upstream of various cytokine gene expression signaling that causes the cytokine-storm.

“eisai is pleased to participate in the groundbreaking remap-covid effort, and we expect that this study will generate important insights about eritoran’s potential to possibly improve health outcomes for patients with moderate and severe covid-19,” said lynn kramer, m.d., faan, chief clinical officer, neurology business group, eisai “as part of our human health care mission, we are committed to making a difference for patients, their families and health care professionals across the globe.”

gcar is the u.s. sponsor of remap-covid and is guiding efforts to facilitate the inclusion of multiple pharma partners in remap-covid globally.

“gcar is delighted to utilize our expertise in implementing and overseeing innovative trials to collaborate on this important effort,” shared meredith buxton, phd, chief executive officer of gcar.  “we are committed to working closely with pharma and the remap network to identify new effective treatments for patients with covid-19 by serving as u.s. sponsor of this important and innovative platform trial.

about remap-cap

remap-cap is led by world experts in critical care, clinical trials, pandemic and infectious disease outbreaks, virology, immunology, emergency medicine, and bayesian statistics. remap-cap has enrolled over 2000 patients at 263 sites across 19 countries. this vital research is being conducted in collaboration with berry consultants, leaders in statistical design for adaptive platform trials, and is being supported by governments and non-profits worldwide.

to learn more about remap-cap and the remap-covid sub-study, please visit  and follow 


about otezla® (apremilast)

otezla® (apremilast) is an oral small-molecule inhibitor of phosphodiesterase 4 (pde4) specific for cyclic adenosine monophosphate (camp). pde4 inhibition results in increased intracellular camp levels, which is thought to indirectly modulate the production of inflammatory mediators. the specific mechanism(s) by which otezla exerts its therapeutic action in patients is not well defined.

by inhibiting pde4, otezla is thought to modulate the production of inflammatory cytokines and other mediators, which may prove helpful in inhibiting the inflammatory response associated with the signs, symptoms and pulmonary involvements observed in some covid-19 patients. amgen plans to collaborate with platform trials to investigate otezla in treatment of hospitalized covid-19 patients.

otezla® (apremilast) u.s. indications

otezla® (apremilast) is indicated for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

otezla is indicated for the treatment of adult patients with active psoriatic arthritis.

otezla is indicated for the treatment of adult patients with oral ulcers associated with behçet’s disease.


otezla® (apremilast) u.s. important safety information

contraindications

  • otezla®(apremilast) is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients in the formulation


warnings and precautions

  • diarrhea, nausea, and vomiting: cases of severe diarrhea, nausea, and vomiting were associated with the use of otezla. most events occurred within the first few weeks of treatment. in some cases patients were hospitalized. patients 65 years of age or older and patients taking medications that can lead to volume depletion or hypotension may be at a higher risk of complications from severe diarrhea, nausea, or vomiting. monitor patients who are more susceptible to complications of diarrhea or vomiting; advise patients to contact their healthcare provider. consider otezla dose reduction or suspension if patients develop severe diarrhea, nausea, or vomiting
  • depression: carefully weigh the risks and benefits of treatment with otezla for patients with a history of depression and/or suicidal thoughts/behavior, or in patients who develop such symptoms while on otezla. patients, caregivers, and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes, and they should contact their healthcare provider if such changes occur

  o psoriasis: treatment with otezla is associated with an increase in depression. during clinical trials, 1.3% (12/920) of patients reported depression compared to 0.4% (2/506) on placebo. depression was reported as serious in 0.1% (1/1308) of patients exposed to otezla, compared to none in placebo-treated patients (0/506). suicidal behavior was observed in 0.1% (1/1308) of patients on otezla, compared to 0.2% (1/506) on placebo. one patient treated with otezla attempted suicide; one patient on placebo committed suicide

  o psoriatic arthritis: treatment with otezla is associated with an increase in depression. during clinical trials, 1.0% (10/998) reported depression or depressed mood compared to 0.8% (4/495) treated with placebo. suicidal ideation and behavior was observed in 0.2% (3/1441) of patients on otezla, compared to none in placebo-treated patients. depression was reported as serious in 0.2% (3/1441) of patients exposed to otezla, compared to none in placebo-treated patients (0/495). two patients who received placebo committed suicide compared to none on otezla

  o  behcet’s disease: treatment with otezla is associated with an increase in depression. during the phase 3 clinical trial, 1% (1/104) reported depression or depressed mood compared to 1% (1/103) treated with placebo. no instances of suicidal ideation or behavior were reported in patients treated with otezla or treated with placebo

  • weight decrease: monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of otezla

  o  psoriasis: during the clinical trials, body weight loss of 5-10% occurred in 12% (96/784) of patients treated with otezla and in 5% (19/382) of patients treated with placebo. body weight loss of ≥10% occurred in 2% (16/784) of patients treated with otezla compared to 1% (3/382) of patients treated with placebo

  o  psoriatic arthritis: during the clinical trials, body weight loss of 5-10% was reported in 10% (49/497) of patients taking otezla and in 3.3% (16/495) of patients taking placebo

  o  behcet’s disease: during the clinical trials, body weight loss of >5% was reported in 4.9% (5/103) of patients taking otezla and in 3.9% (4/102) of patients taking placebo

  • drug interactions: apremilast exposure was decreased when otezla was co-administered with rifampin, a strong cyp450 enzyme inducer; loss of otezla efficacy may occur. concomitant use of otezla with cyp450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended


adverse reactions

  • psoriasis: adverse reactions reported in ≥5% of patients were (otezla%, placebo%): diarrhea (17, 6), nausea (17, 7), upper respiratory tract infection (9, 6), tension headache (8, 4), and headache (6, 4)
  • psoriatic arthritis: adverse reactions reported in at least 2% of patients taking otezla, that occurred at a frequency at least 1% higher than that observed in patients taking placebo, for up to 16 weeks (after the initial 5-day titration), were (otezla%, placebo%): diarrhea (7.7, 1.6); nausea (8.9, 3.1); headache (5.9, 2.2); upper respiratory tract infection (3.9, 1.8); vomiting (3.2, 0.4); nasopharyngitis (2.6, 1.6); upper abdominal pain (2.0, 0.2)
  • behçet’s disease: adverse reactions reported in at least ≥5% of patients taking otezla, that occurred at a frequency at least 1% higher than that observed in patients taking placebo, for up to 12 weeks, were (otezla%, placebo%): diarrhea (41.3, 20.4); nausea (19.2, 10.7); headache (14.4, 10.7); upper respiratory tract infection (11.5, 4.9); upper abdominal pain (8.7, 1.9); vomiting (8.7, 1.9); back pain (7.7, 5.8); viral upper respiratory tract infection (6.7, 4.9); arthralgia (5.8, 2.9)


use in specific populations

  • pregnancy: otezla has not been studied in pregnant women. advise pregnant women of the potential risk of fetal loss. consider pregnancy planning and prevention for females of reproductive potential. there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to otezla during pregnancy. information about the registry can be obtained by calling 1-877-311-8972 or visiting 
  • lactation: there are no data on the presence of apremilast or its metabolites in human milk, the effects of apremilast on the breastfed infant, or the effects of the drug on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for otezla and any potential adverse effects on the breastfed child from otezla or from the underlying maternal condition
  • renal impairment: otezla dosage should be reduced in patients with severe renal impairment (creatinine clearance less than 30 ml/min) for details, see dosage and administration, section 2, in the full prescribing information

please click  for otezla® full prescribing information.

about eritoran (e5564)

eritoran is eisai’s in-house discovered and developed investigational tlr4 (toll-like receptor 4) antagonist created with natural product organic synthesis technology. it is a structural analogue of lipid a which is an activator of endotoxins of bacteria. it has been previously observed to be safe in 14 clinical studies including a large phase 3 randomized trial in severe sepsis. it is expected to suppress inflammation and increasing in severity caused by covid-19 by inhibiting the activation of tlr4, which is found in the most upstream of various cytokine gene expression signaling that causes the cytokine-storm.

about global coalition for adaptive research (gcar)

the global coalition for adaptive research (gcar) is a 501(c)(3) nonprofit organization uniting physicians, clinical researchers, advocacy and philanthropic organizations, biopharma, health authorities, and other key stakeholders in healthcare to expedite the discovery and development of treatments for patients with rare and deadly diseases by serving as sponsor of innovative and complex trials including master protocols and platform trials. in this effort, gcar is serving as u.s. trial sponsor of remap-cap.

to learn more about gcar, visit  and follow us: @gcaresearch and .


about upmc (university of pittsburgh medical center)

pittsburgh-based upmc is inventing new models of patient-centered, cost-effective, accountable care. upmc integrates more than 90,000 employees, 40 hospitals, 700 doctors’ offices and outpatient sites. u.s. news & world report consistently ranks upmc presbyterian shadyside on its annual honor roll of america’s best hospitals and ranks upmc children’s hospital of pittsburgh on its honor roll of america’s best children’s hospitals. for more information, go to .


about amgen 

amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. this approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. a biotechnology pioneer since 1980, amgen has grown to be the world’s largest independent biotec

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) and cogstate, ltd. (headquarters: melbourne, australia and new haven, usa, ceo: brad o’connor, “cogstate”) announced today that the companies have entered into a collaboration whereby eisai has secured the global development rights and exclusive commercialization rights of all cognitive function tests developed by cogstate, including the “cogstate brief batterytm” (cbb) for use in healthcare and other markets. this global licensing deal is an expansion of an existing partnership executed in august 2019 whereby eisai secured exclusive development and commercialization rights in japan for all cognitive function tests developed by cogstate, including the cbb. both companies plan to proceed with development globally of cbb as a tool for individuals to self-assess brain performance to support healthy lifestyle choices and preventative measures in daily life, as well as a medical device to aid healthcare professionals in clinical diagnosis decisions.

developed by cogstate, the cbb is a scientifically validated digital tool that enables cognitive function self-checks and consists of four tests evaluating psychomotor function, attention, learning and memory, and working memory. in the united states, europe, australia, new zealand and canada, the cbb has been adapted as a medical device named “cognigramtm” that has achieved marketing authorization by regulators in these jurisdictions and provides informative results for healthcare professionals to support clinical examination to aid in the diagnosis of mci and dementia.

in its medium-term business plan, eway2025, eisai is aiming to become a “medico societal innovator” (a company that changes society through creating medicines and providing solutions). eisai is creating next-generation medical remedies focused on the neurology and oncology areas as well as building disease ecosystem platforms, in order to provide environments and solutions including digital solutions for early diagnosis and early treatment.

cogstate aims to make assessment of brain health as simple, common and informative as assessment of blood pressure. cogstate’s technology, which is easy to use and available in over 70 languages, is supported by extensive scientific validation, including more than 600 peer reviewed publications. cogstate technology has been used extensively in clinical trials, including trials conducted by eisai.

the global agreement between eisai and cogstate will allow the two companies to replicate many of the advancements that have already been launched in japan, where eisai has developed and launched a new digital tool using the cbb, named “nouknowtm” (pronounced “noh-noh”), a non-medical device for self-assessment of brain performance (brain health). eisai is currently investigating the possibility of developing a medical device using the cbb in japan.

in recent years, various research has demonstrated the possibility that decline in brain performance may be mitigated through major readjustments to lifestyle, such as regular exercise and sleep, a well-balanced diet, and social interaction. however, according to a survey by eisai, the number of people taking correct preventive actions or habitually performing self-checks of cognitive function are few, with disparities (“chasms”) existing against the incorporation of these habits into daily lifestyle.

as a result of these findings, in japan, eisai is constructing a dementia platform, called “easiit”, with the goal of erasing these chasms. core to this platform will be the brain-performance self-check tool “nouknow” and the “easiit app” which aims to contribute to the promotion of health practices through data visualization of brain and body health insights.

it can be expected that the use of “nouknow” to perform periodic self-assessments of brain performance among the generation currently in their prime working years, along with the use of the “easiit app” for the adjustment of lifestyle and practice of preventive measures in daily life, will become an opportunity for the creation of better brain and body health.

through this agreement, eisai and cogstate will work together for the development of digital tools for simpler self-checks of cognitive function and diagnostic tool development for healthcare professionals to promote greater awareness of brain performance globally, thus contributing to the realization of well-being for all.

 

[notes to editors]

1. about eisai co., ltd.

eisai co., ltd. defines 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 to address unmet medical needs, with a particular focus in our strategic areas of neurology and oncology. as a global pharmaceutical company, our mission extends to patients around the world through working with key stakeholders to improve access to medicines in developing and emerging countries.

for further information on eisai co., ltd., please visit 

 

2. about cogstate ltd.

cogstate ltd. (asx:cgs) is a neuroscience technology company headquartered in melbourne, victoria, australia and new haven, connecticut, usa, focused on optimising brain health assessments to advance the development of new medicines and to enable earlier clinical insights in healthcare. since 1999, cogstate technologies have provided rapid, reliable and highly sensitive computerised cognitive tests across a growing list of domains. the company’s clinical trials solutions include quality assurance services for clinical outcome assessments that combine electronic data capture, innovative operational approaches, advanced analytics and scientific consulting. for more than 20 years, cogstate has proudly supported the leading-edge research needs of biopharmaceutical companies and academic institutions and the clinical care needs of physicians and patients around the world. notwithstanding this agreement, cogstate will continue to independently offer its technology and services to the clinical trials market.

for further information on cogstate, please visit .

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that biogen (nasdaq: biib) has disclosed its submission of the marketing authorization application (maa) to the european medicines agency (ema) for the review of aducanumab, an investigational treatment for alzheimer’s disease, as of october 2020 in its q3 2020 earnings press release issued on october 21. this maa is subject to validation of whether the ema accepts the application for review, which biogen plans to announce when notified.

 

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

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that the supplementary new drug applications for its in-house discovered and developed anti-epileptic drug (aed) fycompa® (product name in china: 卫克泰®, generic name: perampanel) as monotherapy for partial-onset seizures and pediatric indication for partial onset seizures in patients with epilepsy 4 years or older have been accepted in china by the national medical products administration.

the submission covering monotherapy for partial-onset seizures was based on subgroup analysis estimating monotherapy safety and efficacy within clinical studies of the combination therapy (study 304, 305, 306, and 335) conducted globally including the united states, europe and china on patients ages 12 years and older with partial-onset seizures (with or without secondarily generalized seizures). additionally, results of a phase iii clinical study (freedom/study 342) conducted in japan and south korea on untreated epilepsy patients ages 12 years to 74 years old with partial-onset seizures (with or without secondarily generalized seizures) were submitted as supplementary safety and efficacy data.

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 conducted globally on pediatric patients (ages 4 to less than 12 years) with inadequately controlled partial-onset seizures or primary generalized tonic-clonic seizures.

in china, it is estimated that there are approximately 9 million patients with epilepsy, and although onset occurs at any age, onset is most common in people aged 18 and younger and the elderly. 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 needs.

fycompa is a first-in-class aed and a once-daily tablet discovered at eisai’s tsukuba research laboratories. the agent is a highly selective, noncompetitive ampa receptor antagonist that reduces neuronal hyper-excitation associated with seizures by targeting glutamate activity at ampa receptors on postsynaptic membranes. fycompa has been approved in china as an adjunctive treatment for partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy 12 years of age and older.

eisai considers neurology, including epilepsy, a therapeutic area of focus. with the acceptance of these additional applications regarding fycompa in china, eisai pursues its mission to provide “seizure freedom” to a greater number of patients with epilepsy across the world. 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 (generic name: 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 drug form to be taken once daily orally at bedtime. a tablet and fine granule formulation have been approved in japan. an oral suspension formulation and tablet have been approved in the united states and europe.

fycompa is currently approved in more than 70 countries and territories, including japan, the united states, china, and other countries in europe and in asia as an 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 65 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, the united states, and south korea, 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.

 

2. about the phase iii clinical studies upon which the additional submission in china covering monotherapy for partial-onset seizures was based

the additional submission covering monotherapy for fycompa in china was based on the results of a phase iii clinical study (study 3352) conducted including japan, china, and south korea, as well as the results of three phase iii clinical studies (study 3043, 3054, and 3065) conducted globally including the united states, europe and china.

study 335 was conducted to evaluate the efficacy and safety of fycompa mainly for the patients in asia region. furthermore, studies 304 and 305 included three arms (placebo, fycompa 8 mg, and 12 mg) and were to evaluate a more extended dose range. the key goal of study 306 was to identify the minimal effective dose and included four treatment arms (placebo, fycompa 2 mg, 4 mg, and 8 mg).

these studies were conducted as the multicenter, randomized, double-blind, placebo-controlled, parallel-group study for the patients aged 12 years and older who have a diagnosis of epilepsy with partial-onset seizures receiving one to a maximum of three anti-epileptic drugs. the primary endpoint of study 335 was the percentage change in seizure frequency. the primary endpoint of study 304, 305, and 306 for the approval in europe was the 50% responder rate (percentage of patients achieving a 50% or greater reduction in seizure frequency compared to pre-randomization phase), while for the approval in the united states it was the percentage change in seizure frequency. specifically, the results showed:

 

1) study 335

  • the percentage changes in seizure frequency shown were -17.3% (p=0.223), -29.0% (p=0.0003), -38.0% (p<0.00001) in the 4, 8, and 12 mg fycompa / day groups, respectively, versus -10.8% with placebo.
  • the most common three adverse events were dizziness, somnolence, and nasopharyngitis.

2) study 304

  • the 50% responder rates compared to placebo were 37.6% (p=0.0760) and 36.1% (p=0.0914) in the 8 mg and 12 mg fycompa / day groups, respectively, versus 26.4% with placebo.
  • the percentage changes in seizure frequency shown were -26.3% (p=0.0261) and -34.5% (p=0.0158) in the 8 mg and 12 mg fycompa / day groups, respectively, versus -21.0% with placebo.
  • the most common six adverse events were dizziness, somnolence, irritability, headache, falls and ataxia.

3) study 305

  • the 50% responder rates compared to placebo were 33.3% (p=0.0018) and 33.9% (p=0.0006) in the 8 mg and 12 mg fycompa / day groups, respectively, versus 14.7% with placebo.
  • the percentage changes in seizure frequency shown were -30.5% (p=0.0008) and -17.6% (p=0.0105) in the 8 mg and 12 mg fycompa / day groups, respectively, versus -9.7% with placebo.
  • the most common four adverse events were dizziness, fatigue, headache, and somnolence.

4) study 306

  • the 50% responder rates compared to placebo were 20.6% (p=0.4863), 28.5% (p=0.0132), and 34.9% (p=0.0003) in the 2, 4, and 8 mg fycompa / day groups, respectively, versus 17.9% with placebo.
  • the percentage changes in seizure frequency shown were -13.6% (p=0.4197), -23.3% (p=0.0026), and -30.8% (p<0.0001), in the 2, 4, and 8 mg fycompa / day groups, respectively, versus -10.7% with placebo.
  • the most common three adverse events were dizziness, headache, and somnolence.

 

3. about freedom (study 342)6

freedom (study 342) is an uncontrolled, open-label phase iii clinical study evaluating efficacy and safety for the fycompa monotherapy conducted in japan and south korea on untreated epilepsy patients aged 12 to 74 with partial-onset seizures with or without secondarily generalized seizures. up to 4 mg of fycompa was taken orally once daily before bedtime (may be titrated up to 8 mg if seizures occur). this study comprised a treatment phase including a titration period of 6 weeks and a maintenance period of 26 weeks (if titrated up from 4 mg to 8 mg, titration period was 4 weeks and maintenance period was 26 weeks) and an extension phase. in this study, 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.

 

4. about study 3117

study 311 is a global (united states, europe, japan, south korea), open-label phase iii clinical study evaluating the safety, tolerability, and exposure efficacy relationship of the fycompa oral suspension when administered as an adjunctive therapy in 180 pediatric epilepsy patients aged 4 to less than 12 with inadequately controlled partial-onset seizures or primary generalized tonic-clonic seizures. this study comprised a treatment phase including a titration period of up to 11 weeks and a maintenance period of up to 12 weeks and an extension phase. in this study, 2 to 16 mg of fycompa was taken orally once daily before bedtime. primary endpoints were safety and tolerability. 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.

 

5. about epilepsy

epilepsy affects approximately 9 million people in china, 1 million people in japan, 3.4 million people in the united states, 6 million people in europe, 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 needs.

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, 
2 nishida t, et al. adjunctive perampanel in partial-onset seizures: asia-pacific, randomized phase iii study. acta neurol scand. 2018;137:392–399.
3 french ja, et al. adjunctive perampanel for refractory partial-onset seizures: randomized phase iii study 304. neurology 2012; 79, 589-596
4 french ja, et al. evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase iii study 305. epilepsia 2013; 54, 117-125.
5 krauss gl, et al. randomized phase iii study 306: adjunctive perampanel for refractory partial-onset seizures. neurology 2012; 78, 1408-1415.
6 yamamoto, takamichi et al. efficacy and safety of perampanel monotherapy in patients with focal-onset seizures with newly diagnosed epilepsy or recurrence of epilepsy after a period of remission: the open-label study 342 (freedom study). epilepsia, 2020; 5, 274-284.
7 fogarasi, andras et al. open-label study to investigate the safety and efficacy of adjunctive perampanel in pediatric patients (4 to <12 years) with inadequately controlled focal seizures or generalized tonic-clonic seizures. epilepsia. 2020; 61, 125-137.

establishment of social cooperation program “protein degradation drug discovery”

 

the university of tokyo (president: makoto gonokami, “the university of tokyo”) and eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today a collaboration aiming for the development and drug discovery of targeted protein degradation technology has been created, with the establishment of a social cooperation program, “protein degradation drug discovery”. the research time span will last five years from october 1, 2020 to september 30, 2025.

the social cooperation program is established and operated based on funds of private organizations dedicated to conducting research in collaboration with the university of tokyo regarding shared issues of high common concern.

the “protein degradation drug discovery” course is to be established within the graduate school of pharmaceutical sciences, the university of tokyo. dr. mikihiko naito, former director of the division of molecular target and gene therapy products, national institute of health sciences, has been inaugurated as a project professor for this program and will lead research with protein degradation technology including sniper. this research will combine the world’s most advanced ubiquitin-proteasome research as conducted in the graduate school with drug discovery knowledge fostered by eisai, for the development of new protein degradation technology towards proteins targeted by drugs and the promotion of drug discovery research based on this technology. in addition, through this research, the course will educate and train the next generation of leaders in this research field.

targeted protein degradation is a series of technologies in which precisely designed compounds force target proteins into proximity with e3 ubiquitin ligase and apply the ubiquitin-proteasome system to induce degradation of the target proteins. the technology provides a means of creating medicines for not only conventional targets such as specific enzymes and receptors, but also disease-related proteins for which drug discovery up to this point has been difficult. through the development of this technology and drug discovery, the university of tokyo and eisai aim to provide new treatment options to patients for which treatment options were previously limited.

 

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

[notes to editors] 
1. about sniper
sniper (specific and nongenetic iap-dependent protein eraser) is a compound which utilizes the ubiquitin-proteasome system to degrade target proteins. this compound is a “hybrid compound”, and consists of a moiety that binds to the target protein and a moiety that binds to e3 ubiquitin ligase (iaps) with an appropriate linker. designing this compound requires advanced medicinal chemistry and cutting-edge structural biology. when the sniper compound brings the target protein and e3 ubiquitin ligase (iaps) into proximity (step 1 in the chart below), ubiquitin as a protein degradation tag transfers from the e2 ubiquitin conjugating enzyme to the target protein (2) for recognition of the protein by the proteasome and subsequent degradation (3).

conventional small-molecule inhibitors bind to the active moiety of target enzymes, and express pharmacological activity by inhibiting the activity thereof. on the other hand, because sniper exhibits pharmacological properties by target protein degradation as described above, it is not only expected to exhibit different pharmacological activity from small-molecule inhibitors; it is also predicted to target proteins that do not have enzymatic activity. similar technologies include protac (proteolysis targeting chimeras) and degronimid.

2. about the ubiquitin-proteasome system
the ubiquitin-proteasome system is one of the naturally occurring mechanisms for controlling the degradation of unneeded proteins, and is in control of critical movements relating to the preservation of life including cell cycle, transcription regulation, and signal transmission. when ubiquitin as a protein degradation tag connects to unneeded proteins through agents such as the e3 ubiquitin ligase, it marks the protein for recognition by the proteasome for subsequent degradation. in recent years, the relation between the ubiquitin-proteasome system and major human diseases including cancer and neurodegeneration is becoming evident.

adopted for the public call for amed “development of therapeutic drugs for the novel coronavirus infection (covid-19)”

 

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that it has entered into a joint research agreement with four research organizations (kan research institute, national center for global health and medicine, nagasaki university, and yokohama city university) in japan concerning the “development of therapeutics to prevent the aggravation of the novel coronavirus infectious disease (covid-19)” (grant number: 20fk0108255), which is a research project with eisai as the representative research organization. this joint research project “development of therapeutics for novel coronavirus infectious disease (covid-19)” was adopted for the second public call by the japan agency for medical research and development (amed) as part of its operation for promotion of the research and development of innovative treatments for emerging and re-emerging infectious diseases in fiscal year 2020.

in patients with covid-19 due to the sars-cov-2 infection, severe cases such as acute respiratory distress syndrome (ards) and subsequent multiple organ failure have been reported. the involvement of the formation and exacerbation of vasculopathy as well as the cytokine storm* in the process of aggravation are assumed. however, at this time, the mechanism of aggravation based on the sars-cov-2 infection is not fully understood.

in this collaborative research, a non-clinical animal model of sars-cov-2 infection will be constructed. additionally, tlr (toll-like receptor) 4 antagonist eritoran, discovered by eisai, and an anti-fkn (fractalkine) antibody e6011, discovered by eisai’s research subsidiary kan research institute, will be evaluated. in addition, this project will promote biomarker research using clinical samples derived from sars-cov-2 infected patients. this collaborative research, aims to elucidate the mechanism of covid-19 aggravation based on sars-cov-2 infection and to create drugs that prevent the aggravation of covid-19.

in the fight against the expansion of covid-19, based on the human health care (hhc) philosophy, eisai will continue the development of therapeutics, stable supply of pharmaceuticals, and support activities in each country.

* cytokine storm: a state of immune runaway, in which the production of cytokines, which play a role in activating the immune response, becomes uncontrollable and cytokines are released in large amounts.

 

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

[notes to editors]

1. about tlr4 and eritoran (e5564)

tlr(toll-like receptor)s are receptors of the innate immune system, and recognize the specific molecular structure of pathogens. it is considered that tlr initiated activation of the innate immune system plays a critical role in eliminating pathogens, causing an inflammatory reaction or an antiviral response. tlr4, one of the tlrs which constitute a family of various receptors, is activated by endotoxins such as lipopolysaccharide released from bacteria. eritoran is eisai’s in-house discovered and developed tlr4 antagonist created by natural product organic synthesis technology. it is a structural analogue of lipid a, which is an active pharmacophore of endotoxins. it has been previously observed to have well-tolerated safety profile in 14 clinical studies including a large phase iii randomized trial in severe sepsis. eritoran has been shown to have the effects of suppressing cytokine production and improving systemic condition in a mouse influenza virus infection model1. it is expected to suppress inflammation and aggravation caused by covid-192,3 by inhibiting the activation of tlr4, which is the most upstream of various cytokine gene expression signaling that causes the cytokine-storm.

eritoran has been selected as the therapeutic drug candidate in the international trial remap-covid for hospitalized patients with moderate covid-19.

2. about fkn and e6011

fkn (fractalkine) is a chemokine that has dual functions of cell migration regulation and cell adhesion, which is induced in vascular endothelial cells during inflammation. the fkn receptor (cx3cr1) is mostly expressed in monocytes, macrophages and killer lymphocytes selectively and plays a key role in efficient collection of cells to the inflamed site. it has been suggested that the fkn-cx3cr1 system relates to various chronic inflammatory diseases including inflammatory bowel disease, rheumatoid arthritis, liver disease, central nervous system disease, arteriosclerosis, dermatosis and others. e6011 is the world’s first humanized anti-fkn monoclonal antibody developed by eisai’s research subsidiary kan research institute, inc., and has a novel action mechanism inhibiting cell invasion by neutralizing activity of fractalkine (fkn), unlike existing cytokine treatments. currently, a phase ii clinical trial in patients with crohn’s disease is being conducted by eisai’s subsidiary for gastrointestinal diseases business ea pharma co., ltd. e6011 inhibits tight binding of cd16 monocytes (cell populations with high cx3cr1 expression), which are important for local inflammatory response, to vascular endothelial cells4. e6011 therefore is expected to suppress the initiation and exacerbation of vasculopathy in covid-195.

1 ka shirey et al., nature. 2013 may 23; 497(7450):498-502
2 p mehta et al., the lancet 2020; 395: 1033-1034
3 c huang et al., the lancet 2020; 395: 497-506
4 y kuboi et al., int immunol. 2019 apr 26;31(5):357
5 h li et al., the lancet 2020; 395: 1517-1520

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 marketing alliance in south korea for si-613 (diclofenac conjugated sodium hyaluronate), a therapeutic agent for osteoarthritis discovered by seikagaku. eisai and seikagaku signed an agreement for the co-development and marketing alliance in china of si-613 on april 1, 2020. thus, south korea becomes the second country for the companies to conclude the marketing alliance for si-613.

on the basis of this agreement, eisai korea inc., eisai’s subsidiary in south korea, will acquire exclusive marketing rights for si-613 in south korea and apply for the manufacturing and marketing approval thereof. after obtaining approval, seikagaku will supply products to eisai, and eisai will be responsible for distribution. eisai will pay seikagaku the upfront payment and 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 the diseases thereof, and the number of patients with knee osteoarthritis in south korea is estimated to be approximately 3.2 million.*1 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 meet the unmet medical needs of patients with knee osteoarthritis by utilizing the knowledge and networks that eisai has cultivated through its korea business. seikagaku will seek to maximize the value of si-613 in south korea by leveraging eisai’s business base in south korea.

through the commercialization of si-613, the companies will provide new treatment options in south korea for knee osteoarthritis and contribute to improving the qol of patients.

1. about si-613

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 effects of sodium hyaluronate. it is expected that si-613 rapidly and continuously reduces the pain and inflammation associated with osteoarthritis (such as knee joint). also, since this is administered directly into the joint cavity by injection, it is considered that the amount of diclofenac systemic exposure and the risk of eliciting systemic adverse drug reaction are to be low.

on january 6, 2020, seikagaku submitted a new drug application (“nda”) for manufacturing and marketing approval of si-613 for osteoarthritis (knee joint, hip joint, and ankle joint) in japan. eisai and seikagaku signed an agreement for the co-development and marketing alliance of si-613 in china on april 1, 2020.

 

2. about eisai co., ltd.

eisai co., ltd. defines 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 to address unmet medical needs, with a particular focus in our strategic areas of neurology and oncology. as a global pharmaceutical company, our mission extends to patients around the world through working with key stakeholders to improve access to medicines in developing and emerging countries.

for further information on eisai co., ltd., please visit 

 

3. about seikagaku corporation

seikagaku corporation is an r&d-oriented pharmaceutical company that focuses on glycoscience as an area of specialization. since its foundation in 1947, seikagaku has continuously focused on the possibilities of glycoscience and developed original, beneficial pharmaceutical products and medical devices in the fields of orthopedic disorders and ophthalmic diseases. under a unique business model of specializing in r&d and manufacturing without having an in-house pharmaceuticals sales division, seikagaku contributes to healthy and fulfilling lives for people around the world by marketing products globally in collaboration with companies having strengths in particular countries and product areas.

for further information on seikagaku corporation, please visit 

 

references:

*1: for the estimated data regarding the number of patients with knee osteoarthritis

  • vital data – korea statistical information service, url : 
  • changes in the number of patients – healthcare bigdata hub, url : 

*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.

filgotinib demonstrates durable efficacy and consistent safety profile through 52 weeks in clinical trials

 

gilead sciences, inc. (nasdaq: gild) and eisai co., ltd. (tokyo, japan) today announced that the japanese ministry of health, labour and welfare (mhlw) has granted gilead k.k. (tokyo, japan) regulatory approval of jyseleca® (filgotinib 200 mg and 100 mg tablets), a once-daily, oral, jak1 preferential inhibitor for the treatment of rheumatoid arthritis (ra) in patients who have had an inadequate response to conventional therapies, including the prevention of structural joint damage.

gilead japan will hold the marketing authorization of jyseleca in japan and will be responsible for product supply of jyseleca in japan, while eisai will be responsible for product distribution of jyseleca in japan in ra. the companies will jointly commercialize the medicine to make it available to physicians and patients across japan.

“despite progress in the treatment of ra, existing therapies have not enabled many patients to reach the treatment goals recommended in clinical guidelines. there continues to be a need for effective and well-tolerated new treatment options,” said tsutomu takeuchi, md, professor of internal medicine and chief of rheumatology at the school of medicine, keio university. “jyseleca is a new jak inhibitor that, in clinical trials, has demonstrated clinical improvement, low disease activity and clinical remission in a broad patient population, including patients with inadequate response to biologics.”

“ra causes many patients debilitating fatigue and pain that can significantly interfere with their daily lives,” said yoshiya tanaka, md, professor at first department of internal medicine, university of occupational and environmental health. “it is important to have new treatment options that can offer patients effective symptom control and bring them new hope.”

the approval in japan is based on robust clinical trial results from the global finch phase 3 and darwin phase 2 programs. the finch and darwin programs evaluated jyseleca in more than 3,500 patients across a range of ra patient populations, including patients new to treatment and those who have demonstrated inadequate response to treatment with standard of care including biologic dmards. patients receiving jyseleca once daily showed improvements in clinical signs and symptoms, decreases in disease activity, and less progression of structural damage in their joints. across the finch trials, jyseleca demonstrated a consistent safety profile, and the frequency of adverse events of interest (including serious infections, herpes zoster, venous thromboembolism and major cardiovascular events) was comparable to control groups.

across the finch and darwin trials, the most common adverse reactions were nausea, upper respiratory tract infection, urinary tract infection and dizziness. rates of herpes zoster and pneumonia were 0.2 percent and 0.3 percent, respectively. the exposure adjusted incidence rate of serious infections per 100 persons per year (95 percent ci) was 1.7 percent (1.3, 2.1) in the jyseleca 200 mg group and 2.5 percent (1.9, 3.3) in the jyseleca 100 mg group, respectively. when prescribing jyseleca, physicians are advised to monitor patients for the development of new, or exacerbation of existing, serious infections including pneumonia, tuberculosis, sepsis and other viral infections.

“this regulatory approval recognizes the benefit that jyseleca may be able to provide people living with ra who have not been successfully treated with prior therapies and represents an important advance in the treatment of this challenging disease,” said luc hermans, md, president and representative director, gilead sciences, k.k.

“now that jyseleca has received approval in japan, we look forward to leveraging our extensive experience in clinical development and commercialization in the ra area in japan to bring this new treatment option to patients across japan as soon as possible, and contribute to the improvement of patients’ quality of life,” said hidenori yabune, president of eisai japan, senior vice president, eisai.

gilead is developing jyseleca in collaboration with galapagos nv (mechelen, belgium (nasdaq and euronext: glpg)). the two companies are conducting global studies investigating the potential role of jyseleca in a variety of diseases, including the previously reported phase 3 selection trial in ulcerative colitis.

 

about the finch program

the finch phase 3 program investigated the efficacy and safety of filgotinib 100 mg and 200 mg once-daily, in ra patient populations ranging from early stage to biologic-experienced patients. finch 1 was a 52-week, randomized, placebo- and adalimumab-controlled trial in combination with mtx, enrolling 1,759 adult patients with moderately to severely active ra who had inadequate response to mtx. the primary endpoint in finch 1 was acr20 at week 12. the trial included radiographic assessment at weeks 24 and 52. finch 2 was a global, 24-week randomized, double-blind, placebo-controlled, phase 3 study evaluating filgotinib on a background of conventional synthetic disease-modifying anti-rheumatic drug(s) (csdmards) among 449 adult patients with moderately to severely active ra who had not adequately responded to biologic dmards (bdmards). the primary endpoint in finch 2 was acr20 at week 12. finch 3 was a 52-week, randomized trial in 1,252 mtx-naïve patients to evaluate filgotinib 200 mg alone and filgotinib 100 mg or 200 mg combined with mtx versus mtx alone. the primary endpoint in finch 3 was acr20 at week 24. the trial included radiographic assessment at weeks 24 and 52.

 

about gilead sciences

gilead sciences, inc. is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. the company strives to transform and simplify care for people with life-threatening illnesses around the world. gilead has operations in more than 35 countries worldwide, with headquarters in foster city, california.

for more information on gilead sciences, please visit the company’s website at .

for more information on gilead sciences k.k., please visit the company’s website at .

 

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 to address unmet medical needs, with a particular focus in our strategic areas of neurology and oncology. as a global pharmaceutical company, our mission extends to patients around the world through our investment and participation in partnership-based initiatives to improve access to medicines in developing and emerging countries.

for more information about eisai co., ltd., please visit 

 

gilead forward-looking statements

this press release includes forward-looking statements within the meaning of the private securities litigation reform act of 1995 that are subject to risks, uncertainties and other factors, including the risk that jyseleca may not be successfully commercialized for the treatment of rheumatoid arthritis in japan. there is also the possibility of unfavorable results from ongoing and additional clinical trials involving jyseleca and the risk that other regulatory authorities may not approve jyseleca for the treatment of rheumatoid arthritis and other indications, and any marketing approvals, if granted, may have significant limitations on its use. further, it is possible that gilead may make a strategic decision to discontinue development and commercialization of jyseleca, and as a result, jyseleca may never be successfully commercialized. these risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. the reader is cautioned not to rely on these forward-looking statements. these and other risks are described in detail in gilead’s quarterly report on form 10-q for the quarter ended june 30, 2020, as filed with the u.s. securities and exchange commission. all forward-looking statements are based on information currently available to gilead, and gilead assumes no obligation to update any such forward-looking statements.

jyseleca®, gilead and the gilead logo are trademarks of gilead sciences, inc. or its related companies.

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced that it has received a positive opinion from the european medicines agency (ema)’s committee for medicinal products for human use (chmp) on the license extension application submitted by its u.k. subsidiary eisai ltd. regarding the use of its in-house discovered and developed anti-epileptic agent (aed) fycompa® (generic name: perampanel) in the treatment of pediatric patients. the chmp’s positive opinion is to extend the use of fycompa as an adjunctive therapy for partial-onset seizures (pos) (with or without secondary generalization) by expanding the approved age range from 12 years and above to 4 years and above, and for primary generalized tonic-clonic seizures (pgtcs) from 12 years and above to 7 years and above.

the application, submitted to ema in february 2019, was based on the results of phase iii (study 311) and phase ii (study 232) clinical studies conducted globally to evaluate fycompa as an adjunctive therapy in pediatric patients with pos or pgtcs. study 311 evaluated the safety, tolerability, and exposure-efficacy relationship of fycompa when administered as an adjunctive therapy in pediatric patients aged 4 to less than 12 years with inadequately controlled pos or pgtcs. study 232 evaluated the pharmacokinetics, efficacy, and long-term safety of fycompa as an adjunctive therapy in pediatric patients with epilepsy (from 2 to less than 12 years of age).

fycompa is a first-in-class aed) and a once-daily tablet discovered at eisai’s tsukuba research laboratories. the agent is a highly selective, noncompetitive ampa receptor antagonist that is postulated to reduce neuronal hyper-excitation associated with seizures by targeting glutamate activity at ampa receptors on postsynaptic membranes. in japan, fycompa is currently approved for monotherapy and adjunctive use in the treatment of pos (with or without secondarily generalized seizures) in patients with epilepsy 4 years of age and older, as well as adjunctive treatment for pgtcs in patients with epilepsy 12 years of age and older. furthermore, fycompa is also indicated for monotherapy and adjunctive use in the treatment of pos (with or without secondarily generalized seizures) in patients with epilepsy 4 years of age and older and for adjunctive therapy in the treatment of pgtcs in patients with epilepsy 12 years of age and older in the united states.

eisai considers neurology, including epilepsy, a therapeutic area of focus. as we offer several treatment options in europe, including fycompa, eisai pursues its mission to provide “seizure freedom” to a greater number of patients 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 (generic name: perampanel)

fycompa is a first-in-class anti-epileptic agent (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. a tablet and fine granule formulation have been approved in japan. an oral suspension formulation and tablet have been approved in the united states and europe.

fycompa is currently approved in more than 70 countries and territories, including japan, the united states, china, and other countries in europe and in asia as an 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 65 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. 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.

 

2. about study 311 1

study 311 is a global (united states, europe, japan, south korea), open-label phase iii clinical study evaluating the safety, tolerability, and exposure efficacy relationship of the fycompa oral suspension when administered as an adjunctive therapy in 180 pediatric epilepsy patients aged 4 to less than 12 with inadequately controlled partial-onset seizures or primary generalized tonic-clonic seizures. this study comprised a treatment phase, including a titration period of up to 11 weeks and a maintenance period of up to 12 weeks and an extension phase. in this study, 2 to 16 mg of fycompa was taken orally once daily before bedtime. primary endpoints were safety and tolerability. 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 2

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

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.

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 aeds,3 this is a disease with significant unmet medical needs. although onset occurs at any age, onset is most common in people aged 18 and younger and the elderly. as causes and clinical symptoms of pediatric epilepsy are not uniform, and prognoses can range from very positive cases to obstinate cases, special consideration for each patient is required of treatments.

1 a. fogarasi et al. open-label study to investigate the safety and efficacy of adjunctive perampanel in pediatric patients (4 to <12 years) with inadequately controlled focal seizures or generalized tonic-clonic seizures epilepsia. 2020 jan;61(1):125-137.
2 j. ben renfroe et al. adjunctive perampanel oral suspension in pediatric patients from ≥2 to <12 years of age with epilepsy: pharmacokinetics, safety, tolerability, and efficacy j child neurol. 2019 apr;34(5):284-294
3 “the epilepsies and seizures: hope through research. what are the epilepsies?” national institute of neurological disorders and stroke, accessed may 24, 2016,

new results include findings from the phase 2 leap-004 trial showing an orr of 21.4% in patients with unresectable or advanced melanoma who had previously progressed on an anti-pd-1/pd-l1 therapy

 

tokyo and kenilworth, n.j.  [september 23, 2020] – eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) and merck & co., inc., kenilworth, n.j., u.s.a. (known as msd outside the united states and canada) announced new investigational data from two trials under the leap (lenvatinib and pembrolizumab) clinical program evaluating lenvima, the orally available multiple receptor tyrosine kinase inhibitor discovered by eisai, plus keytruda, merck’s anti-pd-1 therapy. in the phase 2 leap-004 trial, the lenvima plus keytruda showed an objective response rate (orr) of 21.4% (95% confidence interval (ci): 13.9-30.5) in patients with unresectable or advanced melanoma who had previously progressed on an anti-pd-1/pd-l1 therapy. in the phase 2 leap-005 trial, lenvima plus keytruda demonstrated an orr that ranged from 9.7-32.3% (95% ci: 2.0-51.4) in previously treated patients with triple-negative breast cancer (tnbc), ovarian cancer, gastric cancer, colorectal cancer (non-microsatellite instability-high [non-msi-h]/mismatch repair proficient [pmmr]), glioblastoma multiforme (gbm) and biliary tract cancer (btc). results from leap-004 (abstract #lba44) and leap-005 (abstract #lba41) were accepted as late-breaking abstracts and are being presented in proffered paper presentations at the european society for medical oncology (esmo) virtual congress 2020.

“these new data from our leap clinical program show encouraging activity across several aggressive cancer types and expand our knowledge about the potential of keytruda plus lenvima to help a range of patients with these cancers,” said dr. scot ebbinghaus, vice president, clinical research, merck research laboratories. “this is the first time that clinical data from two leap trials are being presented, reflecting important progress we are making to explore the potential of this combination for patients in need of new options, particularly those with advanced melanoma who have progressed on an anti-pd-1 or pd-l1 therapy.”

“we are encouraged by the growing body of research that we have seen to date, now in 13 different cancers, supporting the potential of the lenvima plus keytruda combination, which we’re currently evaluating in 19 clinical trials,” said dr. takashi owa, chief medicine creation and chief discovery officer, oncology business group at eisai. “these data not only help advance our understanding of the regimen but also fuel our deep-seated determination to work to address the unmet needs of these patients.”
lenvatinib (len) plus pembrolizumab (pembro) for advanced melanoma (mel) that progressed on a pd-1 or pd-l1 inhibitor: initial results of leap-004 (abstract #lba44)

leap-004 (clinicaltrials.gov, ) is a phase 2, single-arm, open-label trial evaluating lenvima in combination with keytruda in patients with unresectable or advanced melanoma who had progressed on an anti-pd-1/pd-l1 therapy within 12 weeks. patients were treated with lenvima 20 mg orally once daily until unacceptable toxicity or disease progression in combination with keytruda 200 mg intravenously every three weeks for up to 35 cycles (approximately two years). the primary endpoint is orr per response evaluation criteria in solid tumors (recist) v1.1 as assessed by blinded independent central review (bicr). secondary endpoints include progression-free survival (pfs) and duration of response (dor) per recist v1.1 by bicr, overall survival (os) and safety.

at data cutoff (june 10, 2020), a total of 103 patients were enrolled and treated. with a median duration of follow-up of 12 months (range: 8.7-15.6), lenvima plus keytruda demonstrated an overall orr by bicr of 21.4% (n=22) (95% ci: 13.9-30.5), with a complete response rate of 1.9% (n=2) and a partial response rate of 19.4% (n=20). in the total study population, the median dor was 6.3 months (range: 2.1 to 11.1 ), with 72.6% (95% ci: 46.2-87.6) of responses lasting for at least six months. median pfs was 4.2 months (95% ci: 3.5-6.3), with 73.8% of patients experiencing disease progression or death, and the nine-month pfs rate was 26.2% (95% ci: 17.4-35.9). median os was 13.9 months (95% ci: 10.8-not reached [nr]), with death occurring in 44.7% of patients, and the nine-month os rate was 65.4% (95% ci: 55.2-73.8).

the exploratory analysis showed that specifically, in the 29 patients whose disease progressed after an anti-pd-1/l1 therapy plus an anti-ctla-4 therapy, the orr by bicr was 31% (95% ci: 15.3-50.8), with a complete response rate of 3.4% (n=1) and a partial response rate of 27.6% (n=8). disease control rate (dcr) by bicr in these patients was 62.1% (95% ci: 42.3-79.3). in the total study population, the dcr by bicr was 65% (95% ci: 55.0-74.2).

treatment-related adverse events (traes) led to discontinuation of lenvima and/or keytruda in 7.8% of patients. grade 3-5 traes occurred in 44.7% of patients (grade 3: 39.8%; grade 4: 3.9%; grade 5: 1.0%), and serious traes occurred in 18.4% of patients. the most common traes of any grade occurring in at least 30% of the overall study population, were hypertension (56.3%), diarrhea (35.9%) nausea (34.0%), hypothyroidism (33.0%) and decreased appetite (31.1%).

 

leap-005: phase 2 study of lenvatinib plus pembrolizumab in patients (pts) with previously treated advanced solid tumors (abstract #lba41)

leap-005 (clinicaltrials.gov, ) is a phase 2, single-arm, open-label trial evaluating lenvima in combination with keytruda in patients with select previously treated advanced solid tumors. the study cohorts are tnbc, ovarian cancer, gastric cancer, colorectal cancer (non-msi-h/pmmr), gbm and btc. patients were treated with lenvima 20 mg orally once daily until unacceptable toxicity or disease progression in combination with keytruda 200 mg intravenously every three weeks for up to 35 cycles (approximately two years). the primary endpoints are orr per recist v1.1 as assessed by bicr or response assessment in neuro-oncology (rano) criteria (for gbm only) as assessed by bicr, and safety. secondary endpoints include dcr per recist v1.1 by bicr or rano (for gbm only) by bicr, dor per recist v1.1 by bicr or rano (for gbm only) by bicr, pfs per recist v1.1 by bicr or rano (for gbm only) by bicr, and os.

at data cutoff (april 10, 2020), a total of 187 patients were enrolled and treated. the confirmed orr after a median duration of follow-up of 8.6 months (range: 1.9-13.1), for the six different tumor types, as well as additional efficacy and safety results, showed:

the most common traes of any grade occurring in at least 20% of the overall study population were hypertension (39.0%), fatigue (29.4%), diarrhea (26.7%), decreased appetite (25.1%), hypothyroidism (27.8%) and nausea (21.9%). based on these initial results, the trial will expand to enroll approximately 100 patients in each cohort.
about lenvima® (lenvatinib) capsules

lenvima, discovered and developed by eisai, is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (vegf) receptors vegfr1 (flt1), vegfr2 (kdr), and vegfr3 (flt4). lenvima inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (fgf) receptors fgfr1-4, the platelet derived growth factor receptor alpha (pdgfrα), kit, and ret. in syngeneic mouse tumor models, lenvatinib decreased tumor-associated macrophages, increased activated cytotoxic t cells, and demonstrated greater antitumor activity in combination with an anti-pd-1 monoclonal antibody compared to either treatment alone. currently, lenvima has been approved for monotherapy as a treatment for thyroid cancer in over 65 countries including japan, the united states, in europe, and in asia, and for unresectable hepatocellular carcinoma in over 65 countries including japan, the united states, in europe, china and in asia. additionally, it is also approved in combination with everolimus as a treatment for renal cell carcinoma following prior antiangiogenic therapy in over 55 countries, including the united states, in europe (where it was launched under the brand name kisplyx® for renal cell carcinoma) and in asia. in addition, it is approved in combination with keytruda as a treatment for patients with advanced endometrial cancer that is not microsatellite instability-high (msi-h) or mismatch repair deficient (dmmr), who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation in countries including the united states, australia, and canada. continued approval for this indication is contingent upon verification and description of clinical benefit in the confirmatory trials.

 

about keytruda® (pembrolizumab) injection

keytruda is an anti-pd-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. keytruda is a humanized monoclonal antibody that blocks the interaction between pd-1 and its ligands, pd-l1 and pd-l2, thereby activating t lymphocytes which may affect both tumor cells and healthy cells.

merck & co., inc., kenilworth, n.j., u.s.a. has the industry’s largest immuno-oncology clinical research program. there are currently more than 1,200 trials studying keytruda across a wide variety of cancers and treatment settings. the keytruda clinical program seeks to understand the role of keytruda across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with keytruda, including exploring several different biomarkers.

 

about the eisai and merck & co., inc., kenilworth, n.j., u.s.a. strategic collaboration

in march 2018, eisai and merck, 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. under the agreement, the companies will jointly develop, manufacture and commercialize lenvima, both as monotherapy and in combination with merck’s anti-pd-1 therapy keytruda.

in addition to ongoing clinical studies evaluating the keytruda plus lenvima combination across several different tumor types, the companies have jointly initiated new clinical studies through the leap (lenvatinib and pembrolizumab) clinical program and are evaluating the combination in 13 different tumor types (endometrial carcinoma, hepatocellular carcinoma, melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, urothelial cancer, biliary tract cancer, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer and triple-negative breast cancer) across 19 clinical trials.

 

eisai’s focus on cancer

eisai focuses on the development of anticancer drugs, targeting the tumor microenvironment (with experience and knowledge from halaven® (eribulin mesylate) and lenvima) and the driver gene mutation and aberrant splicing (leveraging rna splicing platform) as areas (ricchi) where real patient needs are still unmet, and where eisai can become a frontrunner in oncology. eisai will discover innovative new drugs with new targets and mechanisms of action from these ricchi, with the aim of contributing to the cure of cancers.

 

about eisai

eisai is a leading global research and development-based pharmaceutical company headquartered in japan, with approximately 10,000 employees worldwide. 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. we strive to realize our hhc philosophy by delivering innovative products in therapeutic areas with high unmet medical needs, including oncology and neurology. in the spirit of hhc, we take that commitment even further by applying our scientific expertise, clinical capabilities and patient insights to discover and develop innovative solutions that help address society’s toughest unmet needs, including neglected tropical diseases and the sustainable development goals.

for more information about eisai, please visit  (for global), (for u.s.) or  (for europe, middle east, africa), and connect with us on twitter (. and ) and  (for u.s.).

 

merck & co., inc., kenilworth, n.j., u.s.a.’s focus on cancer

our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. at merck & co., inc., kenilworth, n.j., u.s.a., the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. as part of our focus on cancer, merck & co., inc., kenilworth, n.j., u.s.a. is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. we also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. for more information about our oncology clinical trials, visit .

 

about merck & co., inc., kenilworth, n.j., u.s.a.

for more than 125 years, merck & co., inc., kenilworth, n.j., u.s.a., known as msd outside of the united states and canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. we demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. today, merck & co., inc., kenilworth, n.j., u.s.a. continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as hiv and ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. for more information, visit and connect with us on , , ,  and .

 

forward-looking statement of merck & co., inc., kenilworth, n.j., u.s.a.

this news release of merck & co., inc., kenilworth, n.j., u.s.a. (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the u.s. private securities litigation reform act of 1995. these statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. there can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. if underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the recent global outbreak of novel coronavirus disease (covid-19); the impact of pharmaceutical industry regulation and health care legislation in the united states and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

the company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2019 annual report on form 10-k and the company’s other filings with the securities and exchange commission (sec) available at the sec’s internet site ().

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