news – page 11 – eisai china lnc.-nba直播小9直播

news – page 11 – eisai china lnc.-nba直播小9直播

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., nature2013 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 ().

on september 20, 2020, the “2020 ads summit” (ads: advance dementia science) hosted by eisai china inc. was successfully held. featuring the theme of “run into the next decade”, the summit was made up of one main venue (online) and four sub-venues (offline) in beijing, shanghai, guangzhou and chengdu. famous experts from china, japan and south korea and nearly 1,000 guests online and offline made exchanges on the frontier progress of dementia and cognitive disorders. the ads summit is another doctor information exchange platform built by eisai china inc, and is in the third session since it was first held in 2018.

at the beginning of the summit, ms. yanhui feng, senior vice president of eisai global and president of eisai china inc., delivered a speech at the main venue. ms. feng gave a warm welcome to all the experts and guests to the 2020 ads summit and sincerely thanked them for their strong support to the summit. eisai china inc. will devote itself to building an academic exchange platform for cognitive disorders and continue to increase research and development of new drugs in this field. at the same time, adhering to its business philosophy of hhc (human health care), it will work hand in hand with all walks of life to make contributions in disease cognition, prevention and control, patient care and other aspects.


feng yanhui delivered a speech at the main venue (online) 

at this summit, prof. jianping jia from xuanwu hospital of capital medical university was invited as the chairman of the summit. prof. jia expressed thanks to eisai china inc. for setting up such an academic exchange platform that allows chinese, japanese and korean experts and participants to share academic frontier progress and clinical practice, and wished the summit a complete success.

after that, prof. yeon-sil moon from the affiliated hospital of konkuk university in south korea and prof. kenjiro ono from the affiliated hospital of showa university in japan brought the topics of “the most ‘in’ ad biomarkers and applications” and “new drugs for ad are braving the wind and wave” respectively, sharing their professional and in-depth insights with online and offline audiences.

at the sub-venues in beijing, shanghai, guangzhou and chengdu, the hot issues and key topics about dementia and cognitive disorders, such as “2020 aaic hot issues” and “ad whole-process management”, were set. in the “expert sofa show”, a number of experts in the field also made wonderful and valuable comments and hot discussions on topics such as “ad risk factors and prevention guidelines”, “prospects and future of ad treatment”, and “how to conduct whole-process management of ad”. the atmosphere at the scene was warm.


prof. jianping jia chairman of the summit (left), and mr. jianzhong zhang, vice president of eisai china inc. delivered speeches

this summit showed warmly online and offline interaction, and experts and scholars in this field from various regions gathered together, sharing the latest academic frontier progress and clinical practice experience.


sub-venues in beijing, shanghai, guangzhou and chengdu (offline) 

the statistics of the alzheimer’s disease international (adi) in 2019 show that the number of dementia patients in the world has exceeded 50 million, and it is estimated that the number of dementia patients will increase to 152 million by 2050, with one new patient every 3 seconds. in china, the number of dementia patients has exceeded 10 million, and the average survival time of patients is only 5.9 years. however, despite the huge demand for clinical treatment, the pathogenesis of ad is not clear at present, and most of the existing drugs on the market can only relieve symptoms. there is no effective drug to reverse or prevent the progression of the disease so far. moreover, many international clinical trials on ad drugs have failed. therefore, it is still necessary to increase efforts in the research and development of ad therapeutic drugs.

alzheimer’s disease is a disease that eisai has been paying close attention to for a long time. eisai not only introduced donepezil into china and facilitated its inclusion into the medical reimbursement system, but also invested in the research and development of new drugs on a long-term basis. eisai china has always adhered to its business philosophy of hhc (human health care), and has brought rich experience that it has gained in other markets around the world to the chinese market. during the 20 years of its development in china, it has joined forces with all walks of life and enhanced people’s attention to and correct understanding of alzheimer’s disease in the whole chinese society, and benefited patients and their families by carrying out science popularization activities, such as the “remember i love you” alzheimer’s disease philanthropy campaign, “yellow bracelet campaign”, “memory clinic”, and “cognitive college”, etc..

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced that the latest results from the cohort targeting patients with her2-negative breast cancer in the phase i clinical trial for the new liposomal formulation (e7389-lf) of the in-house discovered anti-cancer treatment halaven® (generic name: eribulin mesylate, “eribulin”) were presented (abstract number: 346p) at the european society for medical oncology (esmo) virtual congress 2020.

e7389-lf is a new formulation using liposomes made of a lipid bilayer to encapsulate the halichondrin-class microtubule dynamics inhibitor eribulin. in tumor tissue, gaps exist among vascular endothelial cells due to incomplete vasculature, which is thought to allow for penetration by macromolecules. this condition, in addition to incomplete lymphatic function, is predicted to enable high-molecular-weight drugs including liposomal formulations to be respectively delivered and retained in greater amounts in tumors as compared to in normal tissue, through enhanced permeability and retention (epr) effects. thus e7389-lf is expected to improve the concentration of eribulin in tumor tissues.

this presentation reported efficacy and safety results of e7389-lf in a cohort enrolling 28 patients with recurrent (her2-negative) breast cancer (hormone receptor positive: 21, triple negative: 7) who had previously undergone treatment with anthracycline or taxane class treatments and had no prior treatment with eribulin (data cutoff: january 24, 2020, progression free survival and overall survival cutoff: april 17, 2020), as part of the open-label, phase i clinical trial (study 114) on patients with select solid tumors who had previously undergone treatment. patients were treated with e7389-lf 2.0 mg/m2 body surface area (as free eribulin) intravenously once every three weeks, and demonstrated an overall response rate (orr) of 35.7% (95% confidence interval (ci): 18.6-55.9) in the her2-negative breast cancer cohort as a whole. within the cohort, hormone receptor positive patients demonstrated an orr of 42.9% (95% ci: 21.8-66.6) and triple negative patients demonstrated an orr of 14.3% (95% ci: 0.4-57.9). the disease control rate combining stable disease rate, partial response rate, and complete response rate was 89.3% (95% ci: 71.8-97.7). additionally, progression-free survival (pfs) was a median of 5.7 months (95% ci: 3.9-8.3), and the median overall survival (os) was not reached (95% ci: 10.3 – not reached). adverse events of grade 3 or above (top 5) were neutropenia (67.9%), leukopenia (42.9%), thrombocytopenia (32.1%), febrile neutropenia (25.0%), and increased alanine aminotransferase (21.4%), which were consistent with the safety profile of eribulin to date. additionally, preventive treatment with the g-csf (granulocyte colony stimulating factor) pegfilgrastim demonstrated a decrease in the ratio of febrile neutropenia occurrence (with treatment: 10.0%, without treatment: 33.3%).

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.

 

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

[notes to editors]

1. about e7389-lf

e7389-lf is a new formulation designed for more efficient delivery of the halichondrin-class microtubule dynamics inhibitor “halaven” (eribulin mesylate) into cancer cells by liposome envelopment. a phase i clinical study is currently being conducted on select solid tumors in japan. additionally, a phase ib/ii clinical trial on the combination therapy of e7389-lf and nivolumab targeting select solid tumors is currently being conducted in japan in collaboration with ono pharmaceutical co., ltd.

 

(figure modified with permission from professor nishikawa at tokyo university of science)


2. about halaven (generic name:
 eribulin mesylate)

halaven is in the halichondrin class of microtubule dynamics inhibitors with a novel mechanism of action. structurally, halaven is a simplified and synthetically produced version of halichondrin b, a natural product isolated from the marine sponge halichondria okadai. halaven is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division. in addition, non-clinical studies showed halaven’s unique actions in the tumor microenvironment such as an increase in vascular perfusion and permeability in tumor cores1, promotion of the epithelial state, decrease in capacity of breast cancer cells to migrate2, etc.

halaven was first approved as a treatment in the united states in november 2010 for patients with metastatic breast cancer. halaven is currently approved for use in the treatment of breast cancer in over 75 countries worldwide, including japan, china and countries in europe, the americas and asia. furthermore, halaven was first approved as a treatment for soft tissue sarcoma in the united states in january 2016, and is approved in over 65 countries including japan and in europe and asia. furthermore, halaven has been designated as an orphan drug for soft tissue sarcoma in the united states and japan.
specifically, halaven is approved for the following indications.
in the united states for the treatment of patients with:

  • metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.
  •  unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen.

in japan for the treatment of patients with:

  • inoperable or recurrent breast cancer, soft tissue sarcoma

in europe for the treatment of adult patients with:

  •  locally advanced or metastatic breast cancer who have received a prior anthracycline-containing regimen for advanced disease. prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments.
  •  unresectable liposarcomas who have received prior anthracycline containing therapy (unless unsuitable) for advanced or metastatic disease.

two open-label, randomized, phase iii trials (embrace and study 301) were conducted for halaven in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. based on the pooled analysis of the combined results3, overall survival (os) was extended significantly in the halaven group compared to the control group (hazard ratio 0.85 [95% confidence interval (ci) = 0.77-0.95] p = 0.003, halaven median os: 15.2 months vs. control median os: 12.8 months). progression free survival (pfs) was also extended in the halaven group compared to the control group (hazard ratio 0.90 [95% ci = 0.81-0.997] p = 0.046, halaven median pfs: 4.0 months vs. control median pfs: 3.4 months).

the overall response rate (orr) in the her2-negative breast cancer group was 13.5%. within the group, an orr of hormone receptor positive patients was 14.3% and that of triple negative patients was 12.0%. median pfs in the her2-negative breast cancer group was 4.0 months.

regarding the safety profile from the combined analysis, there were no major differences among the respective clinical studies. patients in these phase iii studies received halaven (1.4 mg/m2 administered intravenously on day 1 and day 8) every 21 days.

1 funahashi y et al., eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models. cancer sci., 2014; 105, 1334-1342
2
 yoshida t et al., eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (emt) to mesenchymal-epithelial transition (met) states. br j cancer, 2014; 110, 1497-1505
3
 twelves c et al., efficacy of eribulin in women with metastatic breast cancer: a pooled analysis of two phase 3 studies. breast cancer res treat, 2014; 148, 553-561

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