news – page 21 – eisai china lnc.-开元体育官网下载手机版

news – page 21 – eisai china lnc.-开元体育官网下载手机版

november 7, 2018, eisai china inc. (eci) held the inauguration ceremony for its new suzhou plant located at no. 168 xingpu road within the suzhou industrial park. mr. kazuyuki katayama (consulate-general of japan in shanghai), mr. yue wang (commissioner of jiangsu food and drug administration), mr. qingwen wu (standing committee of suzhou municipality and secretary general of the party committee of suzhou industrial park administrative committee (sipac)), ms.  yanyan sun (deputy director of sipac), mr. jianmin chen (director-general of suzhou food and drug administration), dr. haruo naito (ceo of eisai co., ltd.), mr. yasushi okada (representative corporate officer of ecl, industry affairs and china business), ms. yanhui feng (vice president of ecl, president of eisai china), mr. norio kaneko (chairman of eisai china) and people with close attention to the development of eisai china attended the ceremony.


ceo haruo naito delivering the speech.

during the address, dr. naito expressed his appreciation for all the government officers and guests attending the inauguration ceremony for the new suzhou plant of eisai china. with the human health care (hhc) corporate philosophy, the quality management policies of eisai are “the quality of every single tablet, capsule and ampoule that we produce is integral to the life of the patient”, aiming to contribute to chinese patients. the construction of the new oral solid dose production facility is to strengthen the stable supply system, and to further expand the contribution to chinese patients. in the further, eisai will bring in new technologies, develop new dosage forms and make the new plant a global manufacturing site spreading innovation. meanwhile, dr. naito emphasized that eisai will commit to the research and development of new drugs, and bring into china more and better drugs like lenvatinib (product name: lenvima®), a first-line treatment for hepatocellular carcinoma (hcc). eisai gives first thought to patients and their families, and seeks to contribute further to increasing the benefits provided to them.

as a part of eisai’s global manufacturing system, the former suzhou plant, located in baiyu road with a floor space of approximately 25,000 m2, was responsible for the local production of solid dosage forms and injections, as well as the sub-packaging of imported products. the total investment was increased to us$110 million in 2004, and the registered capital reached us$38.54 million. to increase the production capacity, the second production facility was established and put into use in 2005. to maintain the business development in china, the total investment was increased to us$230 million in 2010, and the registered capital reached us$78.54 million. in the same year, aiming to get further development, eisai increased investment and established the new suzhou plant on a new industrial site (xingpu road) at approximately 134,000m2 in size, with the construction of administration building, distribution center, parenteral production facility (production capacity: 60 million bottles per year), oral solid dose production facility, and etc. completed successively. the oral solid dose production facility project was started in january 2015, and completed in november 2017, with a size of 23,364m2, and the production capacity (formulation of approximately 3 billion tablets / packaging for approximately 5 billion tablets per year) is approximately double that of the former suzhou plant. on september 14, 2018, the plant acquired gmp certificates for injection and oral solid dose, and formally went into operation.

as one of the main plants, suzhou plant, in addition to satisfy the needs of chinese market, will also provide drugs for 23 countries and regions in east asia, south east asia, middle east, central and south america, europe, and etc.. in recent years, eisai suzhou plant was awarded the “great suzhou best employer”, “top 20 tax payers”, ”top 10 enterprises in headquarters economy”, “top 10 enterprises of foreign regional headquarters”, and etc., successively. the annual sales volume of eisai china remains in the first position among the japanese pharmaceutical enterprises in china.


vip photography

currently, eisai has established 3 companies in suzhou industrial park, namely eci, with its suzhou plant as the most important manufacturing site in china and awarded “major taxpayer in suzhou” for many successive years since its establishment in 1996, eisai (suzhou) trading co., ltd. (est), established in 2010 responsible for eisai’s logistics, warehouse and sales in china, and eisai china holdings ltd. (echl), which was set up in 2014, with investment increased in the next year. eci and est are under the control of echl. in 2015, eisai (liaoning) pharmaceutical co., ltd. was officially established through the full takeover of a local generic drug manufacturer. currently, the total registered capital of eisai in china is us$108.54 million, specializing in neurology, oncology and gastrointestinal areas, with 18 pharmaceutical brands in china’s market. of the 18 brands, 8 ones are locally produced, and the other 5 ones are sub-packaged. until 2017, eisai has nearly two thousand employees in china, and more than one thousand of them are medical representatives taking activities mainly in 4,800 hospitals in over one hundred cities with an urban population of more than one million. in 2017, the annual sales volume of eisai china remained in the first position among the japanese pharmaceutical enterprises in china.

eisai’s business operations in china are one of its core businesses which are third-largest in scale after japan and the united states. with the full-scale commencement of operations at the new suzhou plant, eisai seeks to strengthen its in-house domestic production system in china and expand its stable supply chain of high quality pharmaceuticals, contributing to increasing the benefits to patients and their families in china.


notes to editors
outline of new suzhou plant

location: 168 xingpu road, suzhou industrial park, suzhou, jiangsu, china
site area: approximately 134,000 m2


bird’s eye view of the new suzhou plant

(1) oral solid dose production facility
· floor space: approximately 20,240 m2 / three floors
· main functions: formulation, packaging, storage, etc.
· products to be manufactured: methycobal®, aricept®, pariet® and other products

(2) parenteral production facility
· floor space: approximately 5,690 m2 / two floors
· products manufactured: methycobal® injection and other products

(3) administration building
· floor space: approximately 2,230 m2 / two floors
· main facilities: offices, meeting rooms, cafeteria, etc.

(4) distribution warehouse
· floor space: approximately 7,812 m2 / one floor

on october 27, 2018, the “2018 ads” (ads: advance dementia science) was held by eisai china inc. in beijing, china. the 2018 ads is a communication platform that eisai china established for doctors; the forum covers multi-aspects such as basic researches in the cognitive fields, new methods of diagnosis, clinical hotspots, research and development for new drugs, social and government policies, and etc., with well-known professors from china, japan and south korea discussing and interacting with over 300 participants on-site and over 400 participators online.

at the beginning of the summit, mr. benzhi zhao, deputy secretary general of china population welfare foundation, and ms. yanhui feng, president of eisai china, delivered their speeches. mr. zhao introduced china population welfare fund federation and the progresses of public welfare activities such as yellow bracelets project and etc., and indicated that alzheimer’s disease (ad) is one of the most commonly seen diseases leading to cognitive dysfunction in middle-aged and elderly people, and that through the “yellow bracelets” activity aiming to “bring equal love to both ends of life”, he looked forward to working together with eisai to contribute more to chinese patients in the future. ms. feng showed her warm welcome to all experts and guests in the “2018 ads” and her sincere appreciation for their supports. she said that eisai is committed to building ad-themed academic communication platforms and will continue to increase r&d for new drugs in this field. meanwhile, with its human health care (hhc) corporate philosophy, eisai, together with all sectors of the society, will make more contributions in disease cognition, prevention and control, patient care and other aspects.


from left: benzhi zhao, yanhui feng, jianping jia, xin yu

 

professor jianping jia and professor xin yu were invited to serve as the chairman of the summit. they both expressed their gratitudes to eisai china for building such an academic communication platform, which provides experts from china, japan and korea and the participants with an opportunity to share their frontier academic progresses and clinical practices, and wished the summit a complete success.

in the main session of the frontier progresses of the alzheimer’s disease, experts delivered speeches on topics inclusive of the introduction of the product lines for alzheimer’s disease, the current status and outlook for dementia in china, biomarker diagnosis of alzheimer’s disease, treatment and care for mental behavior symptoms in patients with cognitive impairment, and clinical diagnosis and treatment strategies for cognitive impairment, and etc., discussed the development direction of alzheimer’s disease, shared policies concerning the cognitive disorder management system in china, japan and korea, and talked about continuous drug therapy and appropriate care for dementia patients and more topics. with wide interactions and communications on-site and through online live broadcast, the participants said that they benefited a lot from the summit. in the practice parallel session, presentations and discussions were held on issues in china, japan and south korea, such as the consultation methods of cognitive disorders, new r&d strategies for drugs of alzheimer’s disease, community management for patients with cognitive disorders, and etc. in the clinical hotspots parallel session, academic presentations on the neuropsychological assessment and treatment of aphasia, the whole course management model and practice in alzheimer’s disease patients in china and etc. were conducted, and experts discussions concerning the recommendations and applications of the cognitive assessment system for cerebral small vessel diseases, national stroke registration and baseline data reports of cognitive and sleep subgroups, memory clinic optimization management, select of memory clinic evaluation scales, and the application of memory clinic patient follow-up system etc. were carried out. in the idea exchanges and opinion collisions, the participators harvested the latest academic advances and clinical practices.


2018 ads · beijing summit

in 1906, dr. alzheimer found plaques and fiber tangles in the brain of a patient named auguste d. today, 112 years later; dementia has become a worldwide problem for human beings. the latest data released by world alzheimer report 2015 showed that 1 patient with dementia was diagnosed every 3 seconds in the world. about 50 million people worldwide are suffering from dementia in 2018, and the number is believed to be tripled to 152 million in 2050. alzheimer’s disease is becoming a global crisis as the population ages. raising awareness of the society to alzheimer’s disease and regulating ad diagnosis and treatment process are keys to treat the disease, which requires joint efforts of clinicians, patients, caregivers, and social organizations.

alzheimer’s disease is a field that eisai china has focused for long. it introduces aricept® to china and pushed its entry into china’s national reimbursement drug list while keeping long-term investment in new drugs r&d in this field. adhering to the corporate philosophy of hhc, eisai brings to china its rich experiences that it accumulated in other markets, and endeavors to cooperate with all sectors of the society to increase the social concern and appropriate understanding on alzheimer’s disease in china through carrying out “remember i love you”, a public welfare activity for re-recognizing alzheimer’s disease, the yellow bracelet activity, and etc.

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced that eisai presented new data from study 202, a phase ii evaluation of lemborexant, an investigational sleep-wake regulation agent, for the treatment of irregular sleep-wake rhythm disorder (iswrd) in patients with mild to moderate alzheimer’s disease. the data were presented at the 11th clinical trials in alzheimer’s disease (ctad) conference in barcelona, spain. lemborexant is being developed for the treatment of multiple sleep-wake disorders, including insomnia disorder.

iswrd is a type of circadian rhythm sleep disorder where the pattern of sleep and wakefulness that repeats itself over a 24-hour period in healthy individuals is broken down, and sleeping and waking occur instead at various times during the day and night. this is often observed in patients with neurodegenerative diseases such as alzheimer’s disease. there is no known treatment approved for an irregular sleep-wake pattern in patients, meaning this is a condition with high unmet medical need.

study 202 was a global, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of the efficacy and safety of lemborexant in 62 patients 64 to 89 years of age with iswrd and mild to moderate alzheimer’s disease. the primary objective of this study was to provide proof of concept of lemborexant’s effects on iswrd by evaluating the change from baseline in circadian rhythm-related parameters, nighttime sleep-related parameters and daytime wake-related parameters using actigraphy over four weeks of treatment. an actigraph is a non-invasive device worn on the wrist that incorporates a multidirectional accelerometer to monitor degree and intensity of motion. actigraphs are approved as medical devices that can measure sleep-wake patterns over a 24 hour period by fitting collected activity data into an algorithm.

the study evaluated four doses of lemborexant (2.5mg, 5mg, 10mg and 15mg) versus placebo. treatment with lemborexant resulted in an improved 24-hour circadian rhythm pattern with statistically significant reductions in nighttime activity compared to placebo after four weeks of treatment at three of the four doses tested (2.5mg, 5mg, and 15mg). treatment with lemborexant also helped to consolidate nighttime sleep with positive trends, not statistically significant, for less fragmented and longer total sleep time during the night. finally, the duration of unintentional daytime naps tended to be shorter with lemborexant treatment compared to placebo.

the most common adverse events were constipation, somnolence, arthralgia, headache and nightmare. most adverse events were mild to moderate and infrequent. no patients discontinued the study. there was no change with treatment on cognition as measured by the mini-mental state examination (mmse) or alzheimer’s disease assessment scale for cognition (adas-cog) that would indicate impairment.

“iswrd is a serious and debilitating condition and coupled with dementia puts patients at risk for falls when awake and wandering in the middle of night and poses considerable burden to the family members and caregivers of these patients,” said phyllis zee, md. phd, professor of neurology at northwestern university. “the results of study 202 are encouraging for the potential further development of lemborexant for the treatment of iswrd.”

by acting on the orexin neurotransmitter system, which is the primary regulator of the appropriate balance between sleep and wake at the appropriate circadian times, lemborexant appears to impact the underlying reason for a patient’s inability to sleep well.

“our aspiration is to develop lemborexant as a first-in-class medicine for iswrd to improve sleep and wake patterns for patients with dementia, and as a best-in-class medicine for insomnia disorder” said lynn kramer, md, chief clinical officer and chief medical officer, neurology business group, eisai. “we are encouraged by the results of study 202 in patients with iswrd and as we conduct additional analyses, we will look forward to engaging experts in the field and health authorities regarding a potential path forward for full development, aiming to contribute to patients through lemborexant.”

eisai is striving to create innovative medicines through a holistic and multi-dimensional approach to dementia drug discovery research based on a foundation of over 30 years of experience of drug discovery activities in the area of alzheimer’s disease / dementia. through research and development on lemborexant, eisai is striving to fulfill new unmet medical needs in iswrd and dementia in addition to insomnia to further contribute to increasing the benefit for patients and their families.

 

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

 

[notes to editors]
1. about lemborexant
lemborexant (development code: e2006), a dual orexin receptor antagonist, is an in-house discovered and developed small molecule compound by eisai which inhibits orexin by binding competitively to two subtypes of orexin receptors (orexin receptor 1 and 2). in individuals with insomnia disorder, it is possible that the orexin system which regulates sleep and wakefulness is not functioning normally. during normal periods of sleep, orexin system activity is suppressed, suggesting it is possible to purposefully facilitate the initiation and maintenance of sleep by interfering with orexin neurotransmission with lemborexant.
eisai and purdue pharma are investigating lemborexant as a potential treatment option for sleep-wake disorders. in addition to investigation for the potential treatment of iswrd in patients with alzheimer’s disease, eisai and purdue are developing lemborexant for the treatment of insomnia disorder, and phase iii studies for the treatment of insomnia have now been completed.
information about ongoing clinical studies is available at clinicaltrials.gov.

2. about iswrd (irregular sleep-wake rhythm disorder)
iswrd is a type of circadian rhythm sleep disorder where the pattern of sleep and wakefulness that repeats itself over a 24-hour period in healthy individuals is broken down, and sleeping and waking occur instead at various times during the day and night. this is often observed in patients with dementia. although referred to in this press release as iswrd, the condition is also known as a circadian rhythm sleep disorder – irregular sleep wake type.

3. about study 202
study 202 is a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase ii clinical study (with an open-label extension) of the efficacy and safety of lemborexant in subjects with iswrd and mild to moderate alzheimer’s disease dementia conducted in the united states, japan and the united kingdom. patients with iswrd associated with alzheimer’s disease were administered 2.5 mg, 5 mg, 10 mg or 15 mg of lemborexant or placebo for 4 weeks to determine whether lemborexant would lead to improvement in circadian rhythm, nighttime sleep or daytime wake variables, as measured by actigram. subjects diagnosed with alzheimer’s disease who also met the diagnostic and statistical manual of mental disorders – 5th edition (dsm-5) and the 10th revision of the international classification of diseases (icd-10) criteria for iswrd were screened with actigraphy to ensure current patterns of iswrd, and then were randomized to one of four doses of lemborexant or placebo. actigraphy was recorded continuously during the screening period, for the 1-month treatment period, and a 2-week follow-up period.

4. about actigraphy
an actigraph is a non-invasive device worn on the wrist that incorporates a multidirectional accelerometer to monitor degree and intensity of motion. this device consists of a compact, wrist-worn, battery-operated activity monitor which looks like a wrist watch. actigraphs are approved as medical devices that can measure sleep-wake patterns over a 24 hour period by fitting collected activity data into an algorithm. as innovative endpoints using actigraphy, study 202 evaluated the changes in circadian rhythm-related parameters, nighttime sleep-related parameters and daytime wake-related parameters between baseline and the final week of treatment.

5. about eisai co., ltd.
leveraging the experience gained from the development and marketing of aricept®, a treatment for alzheimer’s disease and dementia with lewy bodies, eisai has been working to establish a social environment that involves patients in each community in cooperation with various stakeholders including the government, healthcare professionals and care workers, and is estimated to have held over ten thousand dementia awareness events worldwide. as a pioneer in the field of dementia treatment, eisai is striving to not only develop next generation treatments but also to develop diagnosis methods and provide solutions. 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 .

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) and biogen inc. (nasdaq: biib) (headquarters: cambridge, massachusetts, united states, ceo: michel vounatsos, “biogen”) announced that eisai presented the latest data from the phase ii clinical study (study 201) of ban2401, an anti-amyloid beta protofibril antibody, in 856 patients with early alzheimer’s disease, at a symposium session titled “clinical and biomarker updates from ban2401 study 201 in early alzheimer’s disease” held on october 25 at the 11th clinical trials on alzheimers disease (ctad) conference in barcelona, spain.

study 201 is a placebo-controlled, double-blind, parallel-group, randomized study in 856 patients with mild cognitive impairment (mci) due to alzheimer’s disease (ad) or mild alzheimer’s dementia (collectively known as early alzheimer’s disease) with confirmed amyloid pathology in the brain. patients were randomized to five dose regimens, 2.5 mg/kg bi-weekly, 5 mg/kg monthly, 5 mg/kg bi-weekly, 10 mg/kg monthly and 10 mg/kg bi-weekly, or placebo. this study used a bayesian adaptive randomization design to automatically allocate newly enrolled patients into the study to treatment arms showing higher probability of efficacy based on the results of interim analyses. the 10 mg/kg monthly and 10 mg/kg bi-weekly doses were determined to have greater efficacy, and as a result, the proportion of patients allocated to those treatment arms was greater.

conventional statistical methods on predefined clinical outcomes at the 18 month final efficacy time point  included alzheimer’s disease composite score (adcoms), alzheimer’s disease assessment scale-cognitive subscale (adas-cog), and clinical dementia rating sum of boxes (cdr-sb).

the most current data presented at ctad 2018 highlight topline results, originally presented by eisai in july at the alzheimer’s association international conference (aaic) 2018, as well as new data from pre-specified subgroup analyses and cerebrospinal fluid (csf) biomarkers. the full ctad presentation is available on the investor relations section of the eisai website.

from conventional statistical analysis of the topline results, the highest treatment dose demonstrated a statistically significant reduction in brain amyloid measured by positron emission tomography (pet)  at 18 months (p<0.0001). this dose also showed a statistically significant slowing of clinical decline on adcoms of 30 percent compared to placebo at 18 months (p=0.034). a group-level correlation between clearance of brain amyloid and slowing of clinical decline on adcoms was confirmed (pearson’s correlation coefficient of 0.838). a linear regression model testing the slope of change from baseline on the rate of disease progression using adcoms showed a significant difference over 18 months (p<0.001) for the highest treatment dose versus placebo, suggesting a potential disease-modifying effect.

a request from a health authority in july 2014 required an amendment to be implemented restricting enrollment of apoe4 carriers in the highest treatment dose arm (10 mg/kg bi-weekly), resulting in an imbalance of apoe4 carriers in that arm versus placebo. to assess the influence of apoe4 status on the observed effect in the highest treatment dose, the rates of clinical decline for apoe4 carriers and non-carriers in the placebo group were analyzed and shown not to be statistically significantly different from each other on adcoms, adas-cog and cdr-sb. analysis on clinical outcome measures was also conducted in pre-specified subgroups of apoe4 status. at the highest treatment dose, apoe4 carriers treated with ban2401 saw 63% less decline in disease progression, while non-carriers saw 7% less decline, as measured by adcoms versus placebo at 18 months. these results suggest that the treatment effect for the 10 mg/kg bi-weekly dose is related to treatment with ban2401 and not due to an imbalance in subject allocation by apoe4 status. in addition, the pooled 10 mg/kg bi-weekly and 10 mg/kg monthly doses result in less decline on adcoms versus placebo at 18 months (overall; 21%, apoe4 carriers; 25%, apoe4 non-carriers; 6%). more detailed results were presented at ctad.

analyses of clinical outcome measures on pre-specified subgroups, by clinical stage and by use of concomitant alzheimer’s disease medications, were also conducted. treatment with the highest treatment dose also resulted in less decline in disease progression on adcoms at 18 months versus placebo across subgroups of clinical stage (mci due to ad subgroup; 33% and mild ad subgroup; 35%) and use of concomitant alzheimer’s disease medications (with concomitant ad meds; 23% and without concomitant ad meds; 41%). the study was not powered to show statistical significance in subgroups.

exploratory data on csf biomarkers of neurodegeneration that are elevated in ad were also presented by eisai. to increase the sample size of the csf subgroup, analyses were conducted on samples from the combined 10 mg/kg bi-weekly and 10 mg/kg monthly cohorts. from the results, markers of synaptic damage (neurogranin), tau pathology (phosphorylated-tau, p-tau), and axonal degeneration (neurofilament light chain, nfl) showed trends that are suggestive of impact on underlying disease pathophysiology.

ban2401 demonstrated an acceptable tolerability profile through 18 months of study drug administration. the most common treatment emergent adverse events were infusion-related reactions and amyloid-related imaging abnormalities (aria), both of which were dose-dependent. incidence of aria-e (edema) was greater in apoe4 carriers. ten percent of aria-e cases (5 of 48 patients) were symptomatic and included headache, visual disturbances, and confusion. sixty percent of aria-e occurred within the first three months of treatment and approximately 89 percent of cases were mild to moderate in severity.

eisai and biogen are currently discussing the next steps for ban2401 with regulatory authorities. an open-label extension for patients previously enrolled in study 201 is being planned, with enrollment expected to begin this year.

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

biogen safe harbor statement 
this press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the private securities litigation reform act of 1995 about results from the phase 2 study of ban2401; the potential clinical effects of ban2401; risks and uncertainties associated with drug development and commercialization; the potential benefits, safety and efficacy of ban2401 and therapies for other neurological diseases; the timing and status of current and future regulatory filings; the anticipated benefits and potential of biogen’s collaboration arrangements with eisai; and the potential of biogen’s commercial business and pipeline programs, including ban2401, elenbecestat and aducanumab. these forward-looking statements may be accompanied by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “potential,” “possible,” “will,” and other words and terms of similar meaning. drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. results in early stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. you should not place undue reliance on these statements or scientific data presented.

these statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation, unexpected concerns that may arise from additional data, analysis, or results obtained during clinical trials; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of biogen’s drug candidates, including ban2401, elenbecestat, and/or aducanumab; the occurrence of adverse safety events; risks of unexpected costs or delays; the risks of other unexpected hurdles; uncertainty of success in the development and potential commercialization of ban2401, elenbecestat, and/or aducanumab, which may be impacted by, among other things, unexpected concerns that may arise from additional data or analysis, the occurrence of adverse safety events, failure to obtain regulatory approvals in certain jurisdictions, failure to protect and enforce biogen’s data, intellectual property and other proprietary rights, and uncertainties relating to intellectual property claims and challenges; uncertainty as to whether the anticipated benefits and potential of biogen’s collaboration arrangement with eisai can be achieved; product liability claims; and third party collaboration risks. the foregoing sets forth many, but not all, of the factors that could cause actual results to differ from biogen’s expectations in any forward-looking statement. investors should consider this cautionary statement, as well as the risk factors identified in biogen’s most recent annual or quarterly report and in other reports biogen has filed with the securities and exchange commission. these statements are based on biogen’s current beliefs and expectations and speak only as of the date of this press release. biogen does not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments, or otherwise.

 

media inquiries

 


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

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

3. about adcoms
developed by eisai, adcoms (ad composite score) combines items from the adas-cog (alzheimer’s disease assessment scale-cognitive subscale), cdr-sb (clinical dementia rating sum of boxes) and the mmse (mini-mental state examination) scales to enable a sensitive detection of changes in clinical functions of early ad symptoms and changes in memory. this study 201 utilizes adcoms as its key endpoint for assessing clinical symptoms.

4. about amyloid pet imaging
amyloid pet (positron emission tomography) imaging is a diagnostic method that enables the visualization of amyloid plaque present in the brain as well as the quantitative evaluation of amyloid plaque distribution and accumulation in the brain via administration of a minute amount of pet tracer, which specifically binds to amyloid plaque. amyloid pet imaging enables the assessment of pathology change and assistance of diagnosis of patients with alzheimer’s disease, including mci due to ad, and could predict clinical response.

5. about correlation coefficient
the correlation coefficient indicates the strength of the relationship between two variables from two quantitative data distributions. the correlation coefficient ranges in value from -1 to 1, and as it approaches the absolute value of 1, it indicates a total positive linear correlation. in general, if a correlation coefficient is 0.6 or greater, it suggests there is a relationship between the variables.

6. about the joint development agreement between eisai and biogen for alzheimer’s disease
eisai and biogen are widely collaborating on the joint development and commercialization of alzheimer’s disease treatments. eisai serves as the lead in the co-development of elenbecestat, a bace inhibitor, and ban2401, an anti-amyloid beta (aβ) protofibril antibody, while biogen serves as the lead for co-development of aducanumab, biogen’s investigational anti-amyloid beta (aβ) antibody for patients with alzheimer’s disease, and the companies plan to pursue marketing authorizations for the three compounds worldwide. if approved, the companies will also co-promote the products in major markets, such as the united states, the european union and japan.

as to ban2401 and elenbecestat, both companies will equally split overall costs, including research and development expenses. eisai will book all sales for elenbecestat and ban2401 following marketing approval and launch, and profits will be equally shared between the companies.

7. 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.

leveraging the experience gained from the development and marketing of aricept®, a treatment for alzheimer’s disease and dementia with lewy bodies, eisai has been working to establish a social environment that involves patients in each community in cooperation with various stakeholders including the government, healthcare professionals and care workers, and is estimated to have held over ten thousand dementia awareness events worldwide. as a pioneer in the field of dementia treatment, eisai is striving to not only develop next generation treatments but also to develop diagnosis methods and provide solutions.

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

8. about biogen
at biogen, our mission is clear: we are pioneers in neuroscience. biogen discovers, develops and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases. one of the world’s first global biotechnology companies, biogen was founded in 1978 by charles weissmann, heinz schaller, kenneth murray and nobel prize winners walter gilbert and phillip sharp, and today has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first and only approved treatment for spinal muscular atrophy and is focused on advancing neuroscience research programs in alzheimer’s disease and dementia, multiple sclerosis and neuroimmunology, movement disorders, neuromuscular disorders, pain, ophthalmology, neuropsychiatry and acute neurology. biogen also manufactures and commercializes biosimilars of advanced biologics.

we routinely post information that may be important to investors on our website at . to learn more, please visit  and follow us on social media – , , , .

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

on october 23, 2018, eisai china inc. was invited to attend the “health to countryside” activity held in duyun city, qiannan autonomous prefecture, guizhou province by the national committee for education, science, culture, health and sports of chinese people’s political consultative conference (cppcc), and donated medicines worth rmb510,000 yuan to the local health commission. eisai china acts in accordance with the corporate philosophy of human health care (hhc) and practices social responsibilities all along, donating medicines worth rmb450,000, rmb490,000, rmb500,000, rmb540,000 and rmb510,000 respectively to this project from the year 2014 to 2018, with the total worth of medicines reaching up to approximately rmb2.5 million yuan.


the honorary credential granted to eisai china inc.

to implement the spirit of relevant documents of the state council, the national committee for education, science, culture, health and sports of cppcc organized, along with chinese pharmaceutical association, chinese medical association, and chinese academy of medical sciences this “health to countryside” activity in qiannan autonomous prefecture, guizhou province. “health to countryside” is an important and traditional activity carried out by the national committee for education, science, culture, health and sports of cppcc every year, implementing cppcc’s articles. this activity not only delivers doctors, medicines, concepts, technologies and management to the grassroots, but also narrows the distance between the committee members, the experts and the masses.

eisai china recommends that all of its employees spend about 1% of their business time every year with patients practicing the hhc philosophy, for the simple fact that only having the empathy with patients’ feelings and pains can eisai provide better service as well as products in need to earn the trust from patients and their families. eisai china will, led by its chairman mr. norio kaneko and the president ms. yanhui feng, constantly contribute to the medical and health service in poor areas by engaging the “health to countryside” activity.

additional data from ban2401 phase ii results to be presented in symposium session

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that five oral presentations including a symposium, and two poster presentations, highlighting the latest data on its alzheimer’s disease / dementia pipeline including anti-amyloid beta (aβ) protofibril antibody ban2401, oral beta secretase cleaving enzyme (bace) inhibitor elenbecestat, anti-aβ antibody aducanumab, and dual orexin receptor antagonist lemborexant, will be given at the 11th clinical trials on alzheimer’s disease (ctad) conference taking place in barcelona, spain, from october 24 to 27. ban2401, elenbecestat and aducanumab are being jointly developed by eisai and biogen inc. (headquarters: cambridge, massachusetts, united states, “biogen”).

for ban2401, a one-hour presentation will be given as a symposium to provide clinical and biomarker updates to the results initially presented in july 2018 from study 201 in patients with early alzheimer’s disease (mild cognitive impairment due to alzheimer’s disease or mild alzheimer’s disease dementia). the ban2401 presentation will be webcast live. to access the live webcasts, please visit the investors section of eisai’s website on the day at .

there will be an oral elenbecestat presentation which will include additional data on the study 202 results that were initially presented in july 2018 in patients with mild cognitive impairment and mild to moderate alzheimer’s disease. elenbecestat is currently being investigated in two ongoing phase iii clinical studies (mission ad1/2) in patients with early alzheimer’s disease.

meanwhile, for aducanumab, there will be several presentations on late breaking abstracts  including the results of analyses of cumulative safety data from the phase ib study prime long-term extension study of patients with early alzheimer’s disease  initially announced in august 2018. currently, eisai and biogen are advancing two phase iii clinical studies (engage/emerge) on aducanumab.

in addition, there will be a presentation on data from a first-in-kind phase ii clinical study (study 202) on the investigational sleep-wake regulation agent lemborexant in alzheimer’s disease patients with irregular sleep-wake rhythm disorder (iswrd). discovered by eisai, lemborexant has been jointly developed with purdue pharma l.p. (headquarters: connecticut, united states, “purdue pharma”) since august 2015.

eisai is aiming to realize prevention and cure of dementia through a holistic approach to dementia drug discovery research based on a foundation of over 30 years of experience of drug discovery activities in the area of alzheimer’s disease / dementia. eisai is striving to create innovative medicines as soon as possible in order to further contribute to addressing the unmet medical needs of, as well as increasing the benefits provided to, patients and their families.

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

 

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

2. about elenbecestat (generic name, development code: e2609)
elenbecestat is an oral bace (beta amyloid cleaving enzyme) inhibitor currently being investigated in phase ⅲ clinical studies for alzheimer’s disease discovered by eisai. by inhibiting bace, a key enzyme in the production of aβ peptides, elenbecestat reduces aβ production, which is thought to lead to a reduction in amyloid plaque formations caused by the aggregation of toxic oligomers and protofibrils in the brain. currently, two global phase iii clinical studies (mission ad1/2) of elenbecestat in early alzheimer’s disease including mild cognitive impairment (mci) due to ad/prodromal ad and the early stages of mild ad are underway. in addition, the u.s. food and drug administration (fda) has granted fast track designation for the development of elenbecestat, a process to facilitate development and expedite review by fda for drugs deemed as having potential to treat serious conditions and addressing unmet medical needs.

3. about aducanumab (biib037)
aducanumab is an investigational compound being developed for the treatment of alzheimer’s disease. aducanumab is a human recombinant monoclonal antibody (mab) derived from a de-identified library of b cells collected from healthy elderly subjects with no signs of cognitive impairment or cognitively impaired elderly subjects with unusually slow cognitive decline using neurimmune’s technology platform called reverse translational medicine (rtm). biogen licensed aducanumab from neurimmune under a collaborative development and license agreement.

aducanumab is thought to target aggregated forms of beta amyloid including soluble oligomers and insoluble fibrils which can form into amyloid plaque in the brain of alzheimer’s disease patients. based on pre-clinical and phase 1b data to date, treatment with aducanumab has been shown to reduce amyloid plaque levels.

in august 2016 aducanumab was accepted into the european medicines agency’s prime program. in september 2016 the u.s. food and drug administration accepted aducanumab into its fast track program and in april 2017 aducanumab was accepted into the japanese ministry of health, labour and welfare’s (mhlw) sakigake designation system.

4. about the joint development agreement between eisai and biogen for alzheimer’s disease
eisai and biogen are widely collaborating on the joint development and commercialization of alzheimer’s disease treatments. eisai serves as the lead in the co-development of elenbecestat, a bace inhibitor, and ban2401, an anti-aβ protofibril antibody, while biogen serves as the lead for co-development of aducanumab, biogen’s investigational anti-aβ antibody for patients with alzheimer’s disease, and the companies plan to pursue marketing authorizations for the three compounds worldwide. if approved, the companies will also co-promote the products in major markets, such as the united states, the european union and japan.

5. about lemborexant (generic name, development code: e2006)
lemborexant, a dual orexin receptor antagonist, is eisai’s in-house discovered and developed small molecule compound that inhibits orexin neurotransmission by binding competitively to the two subtypes of orexin receptors (orexin receptor 1 and 2). in individuals with sleep disorders, it is possible that the orexin system that regulates sleep and wakefulness is not functioning normally. during normal periods of sleep, orexin system activity is suppressed, suggesting it is possible to purposefully counteract inappropriate wakefulness and facilitate the initiation and maintenance of sleep by interfering with orexin neurotransmission. therefore, eisai and purdue have been developing lemborexant as a treatment for multiple sleep disorders.

in addition, a phase ii clinical study of lemborexant in patients with irregular sleep-wake rhythm disorder (iswrd) and mild to moderate alzheimer’s dementia is underway.

long-term efficacy and safety evaluation in patients with insomnia, a sleep-wake disorder, met primary and key secondary efficacy objectives 

tokyo and stamford, conn. – october 17, 2018 – eisai co., ltd. (ceo: haruo naito, “eisai”) and purdue pharma l.p. (president and ceo: craig landau, “purdue pharma”) today announced positive topline results from sunrise 2, a long-term phase 3 efficacy and safety evaluation of lemborexant, an investigational agent for sleep-wake regulation currently being studied for the potential treatment of multiple sleep-wake disorders. topline results reported today are the primary and key secondary outcomes of the study from the six-month, placebo-controlled treatment period; the study is ongoing to 12 months. eisai and purdue pharma plan to present full results from sunrise 2 at upcoming medical meetings in 2019.

sunrise 2 enrolled more than 900 adult patients (18 to 88 years of age) with insomnia disorder, characterized by difficulty falling asleep and/or staying asleep. the study met the pre-specified primary and key secondary efficacy objectives assessed by patient self-reports (sleep diaries). at the end of the six-month, placebo-controlled treatment period, lemborexant 5 mg and 10 mg provided statistically significant improvement in subjective sleep onset latency compared to placebo, the study’s primary endpoint. lemborexant 5 mg and 10 mg also provided statistically significant improvement in sleep maintenance variables of subjective sleep efficiency and subjective wake after sleep onset compared to placebo, which were the study’s key secondary endpoints. daily functioning, as measured by the insomnia severity index, was also improved by both lemborexant 5 mg and 10 mg compared to placebo. the most common adverse events (aes), greater than 5 percent in either lemborexant treatment arm and greater than placebo, were somnolence, headache, and influenza. overall discontinuation rates due to aes were comparable between placebo and lemborexant 5 mg, and higher for lemborexant 10 mg.

“as a clinician and researcher treating patients with insomnia and other sleep-wake disorders for 30 years, for me, successful treatment means that patients fall asleep fast, sleep well, and wake well, without functional impairment, or loss of effect over time,” said russell rosenberg, phd, d.absm, a principal investigator in the lemborexant studies and former chairman of the board of the national sleep foundation. “the results of sunrise 2 are particularly encouraging for the many patients who suffer from chronic insomnia.”

the results of sunrise 2 build on a growing body of knowledge supporting the development of lemborexant, including sunrise 1, a recently completed phase 3 study of lemborexant 5 mg and 10 mg versus placebo, including a superiority comparison to zolpidem tartrate extended release (zolpidem er) as a secondary endpoint, as well as key safety studies evaluating for impairment as assessed by the ability to maintain postural stability – a predictor of risk for falls – after middle-of-the-night and next morning awakening and next-morning driving performance.

“our aspiration for lemborexant is to bring to the millions of patients suffering from insomnia and other sleep-wake disorders an agent for sleep-wake regulation that improves their ability to fall asleep and stay asleep, and maintains efficacy over time,” said lynn kramer, md, chief clinical officer and chief medical officer, neurology business group, eisai. “in sunrise 2, lemborexant improved time to sleep onset and sleep maintenance over a six-month period. with these results, we now look forward to proceeding with regulatory submissions for lemborexant to bring to patients a long-term treatment option for treating the sleep-wake disorder, insomnia.”

lemborexant acts on the orexin neurotransmitter system and is believed to regulate sleep and wake by dampening wakefulness without impeding the ability to awaken to external stimuli.

“we understand the importance of sleep-wake regulation to overall health and patient outcomes and, alongside our collaboration partner, eisai, look forward to continued research as part of our commitment to a variety of patient populations with sleep-wake disorders,” said marcelo bigal, md, phd, chief medical officer, purdue pharma.

discovered by eisai, lemborexant is being jointly developed by eisai and purdue pharma. information about ongoing clinical studies is available at clinicaltrials.gov.

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

 

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

 

1. about lemborexant
lemborexant, an investigational dual orexin receptor antagonist, is eisai’s in-house discovered and developed small molecule compound which inhibits orexin neurotransmission, or signaling, by binding competitively to two subtypes of orexin receptors (orexin receptor 1 and 2). in individuals with sleep-wake disorders, it is possible that the orexin system which regulates wakefulness is not functioning normally. during normal periods of sleep, orexin system activity is suppressed, suggesting it is possible to purposefully counteract inappropriate wakefulness and facilitate the initiation and maintenance of sleep.

eisai and purdue pharma are investigating lemborexant as a potential treatment option for insomnia and other sleep-wake disorders. a phase 2 clinical study of lemborexant in patients with irregular sleep-wake rhythm disorder and mild to moderate alzheimer’s dementia is underway.

2. about sunrise 2 / study 3031
a 12-month multicenter, global, randomized, controlled, double-blind, parallel group study of 971 male or female adult participants (18 to 88 years of age) with insomnia disorder, including a screening and two-week placebo run-in period, a 52-week treatment period and a two-week follow-up period. all patients received lemborexant for at least six months during the study. lemborexant 5 mg, 10 mg or matching placebo was taken orally in tablet form at home each night immediately before the patient intended to try to sleep for the first six months of study. the primary outcome measure was mean change from baseline in subjective sleep onset latency after six months of placebo-controlled treatment. key secondary outcome measures were mean change from baseline in subjective sleep efficiency and subjective wake after sleep onset after six months of placebo-controlled treatment.

3. about sleep disorders

population studies show that sleep disorders affect many more people worldwide than previously thought.1 insomnia disorder is characterized by difficulty falling sleep, staying asleep or both, despite an adequate opportunity to sleep, that can lead to daytime consequences such as fatigue, difficulty concentrating and irritability.3,4 insomnia disorder is the most common sleep disorder, with persistent insomnia symptoms experienced by approximately 10 percent of the adult population.2,3
sleeping well is essential for good health, including brain health. poor sleep is associated with a wide range of health consequences, including an increased risk of hypertension, accidental injury, diabetes, obesity, depression, heart attack, stroke and dementia, as well as adverse effects on mood and behavior.4,5
experimental studies in animals and humans provide evidence of associations between sleep and disease risk factors, diseases and mortality.2,6 studies suggest an optimal sleep duration between seven and eight hours.2,6 women are 1.4 times more likely than men to suffer from insomnia.7
older adults also have higher prevalence of insomnia; aging is often accompanied by changes in sleep patterns, including disrupted sleep, frequent waking and early waking, that can lead to less sleep time.8
4. about eisai co., ltd

eisai co., ltd. is a leading global research and development-based pharmaceutical company headquartered in japan. we define our corporate mission as “giving first thought to patients and their families and to increasing the benefits health care provides,” which we call our human health care (hhc) philosophy. with approximately 10,000 employees working across our global network of r&d facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products to address unmet medical needs, with a particular focus in our strategic areas of oncology and neurology.
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 .


5. about purdue pharma l.p.

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

references
1
 eisai inc. long-term study of lemborexant in insomnia disorder (e2006-g000-303). available from  nlm identifier: nct02952820.
2
 ferrie je, et al. sleep epidemiology – a rapidly growing field. int j epidemiol. 2011;40(6):1431–1437.
3
 ohayon mm, et al. epidemiology of insomnia: what we know and what we still need to learn. sleep med rev. 2002;6(2):97-111.
4 institute of medicine. sleep disorders and sleep deprivation: an unmet public health problem. washington, dc: national academies press. 2006.
5
 pase mp, himali jj, grima na, et al. sleep architecture and the risk of incident dementia in the community. neurology. 2017;89(12):1244-1250.
6
 trenell mi, et al. sleep and metabolic control: waking to a problem? clin exp pharmacol physiol. 2007;34:1-9.
7 zhang b, wing, yk. sex differences in insomnia: a meta-analysis. sleep. 2006;29(1):85-93.
8 ohayon mm, et al. meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan. sleep. 2004;27:1255-1273.

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) has announced that the national medical products administration of china has accepted for review a new drug application for eisai’s antiepileptic drug (aed) perampanel (generic name, product name: fycompa®) as an adjunctive treatment for partial onset seizures in epilepsy patients 12 years of age and older. this nda is the first to be submitted for perampanel in china.

this application for perampanel in partial onset seizures in china was based on the results of three phase iii clinical studies conducted mainly in europe and the united states, as well as the results of a phase iii clinical study (study 335) conducted mainly in asia including china and japan.
in china it is estimated that there are approximately 9 million patients with epilepsy, with approximately 60% being affected by partial-onset seizures, and 40% of these patients with partial-onset seizures require adjunctive treatment.1 as approximately 30% of patients with epilepsy are unable to control their seizures with currently available aeds,2 this is a disease with significant unmet medical need.

perampanel is a first-in-class aed discovered at eisai’s tsukuba research laboratories. administered orally once-daily, it is a highly selective, noncompetitive ampa receptor antagonist that reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity at ampa receptors on postsynaptic membranes.

perampanel has been approved in over 55 countries around the world 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, perampanel has been approved in over 50 countries around the world as an adjunctive treatment for primary generalized tonic clonic seizures in patients with epilepsy 12 years of age and older. in the united states, perampanel is also indicated 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.

eisai considers neurology including epilepsy, a therapeutic area of focus, and is striving to deliver perampanel to patients in china as soon as possible. in pursuit of our mission to provide “seizure freedom” to a greater number of patients living with epilepsy, eisai seeks to address the diverse needs of, as well as increasing the benefits provided to, patients with epilepsy and their families.

 

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

 

[notes to editors]
1. about perampanel (generic name, product name: fycompa)
perampanel is a first-in-class aed discovered and developed by eisai. with epileptic seizures being mediated by the neurotransmitter glutamate, the agent is a highly selective, noncompetitive ampa receptor antagonist that reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity at ampa receptors on postsynaptic membranes. perampanel is available in tablet form to be taken once daily orally at bedtime. in addition, an oral suspension formulation has been approved in the united states.

perampanel is currently approved in more than 55 countries and territories, including the united states, japan, in europe and in asia as adjunctive treatment for partial-onset seizures (with or without secondarily generalized seizures) in patients with epilepsy 12 years of age and older. an application seeking approval for use in the treatment of partial-onset seizures has now been filed in china. in addition, perampanel has been approved in more than 50 countries, including the united states, japan, in europe and in asia for treatment as an adjunctive therapy for primary generalized tonic clonic seizures in patients with epilepsy 12 years of age and older. in the united states, perampanel is also indicated 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.

furthermore, eisai is conducting a global phase iii clinical study (study 338) for the agent in patients with seizures associated with lennox-gastaut syndrome. in japan and europe, eisai is conducting a phase iii study in pediatric patients with epilepsy (study 311). additionally, a phase iii study of perampanel as monotherapy in untreated patients with partial-onset seizures 12 years of age and older is being conducted in japan (study 342).

 

2. about study 335 upon which the nda in china was based3

study title: a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of perampanel administered as an adjunctive therapy in subjects with refractory partial-onset seizures
study population: 710 patients aged 12 years and older who have a diagnosis of epilepsy with partial-onset seizures with or without secondarily generalized seizures receiving one to a maximum of three anti-epileptic drugs
treatment administered: perampanel oral tablets, 4 mg/day, 8 mg/day and 12 mg/day, once daily before bedtime

perampanel-matched placebo oral tablets, once daily before bedtime

duration of treatment: prerandomization phase: 6 weeks

randomization phase (treatment): 19 weeks

(titration period, 6 weeks; maintenance period, 13 weeks)

extension phase: over 10 weeks

study locations: japan, china, south korea, australia, thailand, malaysia, chinese taiwan
primary endpoint: percent change in seizure frequency per 28 days during treatment relative to baseline
results: the percent change in seizure frequency in the placebo group was -10.8% while in the perampanel (4 mg, 8 mg, 12 mg) groups it was -17.3%, -29.0% and -38.0%, respectively. the difference between perampanel and placebo was statistically significant for the perampanel 8 and 12 mg groups (p=0.0003 for 8 mg, p<0.0001 for 12 mg).
adverse events: the most common adverse events (≥10% in the perampanel arms and greater than placebo) were dizziness (22.7%, 28.6%, 42.2% in the perampanel 4 mg, 8 mg, 12 mg groups respectively and 5.7% for placebo) and somnolence (15.9%, 17.7%, 17.8% in the perampanel 4 mg, 8 mg, 12 mg groups respectively and 13.1% for placebo).


3. about epilepsy

epilepsy affects approximately 3.4 million people in the united states, 1 million people in japan, 6 million people in europe, 9 million people in china, and approximately 60 million people worldwide. as approximately 30% of patients with epilepsy are unable to control their seizures with currently available aeds,2 this is a disease with significant unmet medical need.

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

 

1  clinical guideline 2015 in china
2  “the epilepsies and seizures: hope through research. what are the epilepsies?” national institute of neurological disorders and stroke, accessed may 24, 2016, 
3  nishida t., et al. adjunctive perampanel in partial-onset seizures: asia-pacific, randomized phase iii study. acta neurol scand. 2018; 137:392-399

first approval for lenvima in china and first new therapy for the first-line treatment of unresectable hcc approved in china in a decade

tokyo and kenilworth, n.j. sept. 5, 2018 – eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) and merck & co., inc., kenilworth n.j., u.s.a., known as msd outside of the united states and canada, announced today that the china national medical products administration (nmpa) approved the kinase inhibitor lenvima® (lenvatinib) as a single agent for the treatment of patients with unresectable hepatocellular carcinoma (hcc) who have not received prior systemic therapy. in china, the application of lenvima was submitted in october 2017, and was designated for priority review by the nmpa due to lenvima’s significant clinical benefit compared to existing treatments, leading to approval in approximately 10 months. this approval marks the first for lenvima in china, where the incidence of hcc is high,1 and the first new systemic therapy approved for the first-line treatment of unresectable hcc in china in ten years.1

the approval was based on results from the reflect study (study 304)2, an open-label, phase 3 trial where lenvima demonstrated a treatment effect on overall survival (os) by statistical confirmation of non-inferiority when compared with the standard of care, sorafenib, in 954 patients with previously untreated unresectable hcc. lenvima demonstrated statistically significant superiority and clinically meaningful improvements in progression-free survival (pfs), time to progression (ttp) and objective response rate (orr). in a subpopulation analysis of 288 patients in the study from the greater chinese region (mainland china, hksa and chinese taiwan), lenvima demonstrated efficacy based on non-inferiority of os compared to sorafenib, with improvements also observed in pfs, ttp and orr3. approximately 80% of patients in the subpopulation were living with hcc resulting from chronic hepatitis b virus (hbv), which has high unmet medical need. for these patients, lenvima demonstrated non-inferiority based on os compared with sorafenib, thereby demonstrating the effect of lenvima in patients with hcc resulting from hbv. (for the detailed data, please refer to “notes for editors” below.)

in the china package insert, the five most common adverse reactions observed in patients treated with lenvima were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%) and decreased weight (31%), which is consistent with the known side-effect profile of lenvima.

liver cancer is the second leading cause of cancer-related deaths and is estimated to be responsible for approximately 750,000 deaths per year globally. additionally, approximately 780,000 cases are newly diagnosed each year, about 80% of which occur in asian regions. specifically, in china, there are approximately 395,000 new cases and 380,000 deaths per year, accounting for approximately 50% of cases worldwide.1 hcc accounts for 85% to 90% of primary liver cancer cases. unresectable hcc, for which treatment options are limited, is extremely difficult to treat, and the development of new treatments is necessary.

since the initial launch, more than 10,000 patients have been treated with lenvima. today, lenvima is approved as a treatment for refractory thyroid cancer in over 50 countries including the united states, japan, in europe and asia, and as combination with everolimus as a second-line treatment for renal cell carcinoma (rcc) in over 45 countries including the united states and in europe. for hcc, lenvima was approved for use in japan in march 2018, and in the united states and europe in august 2018. in japan, approximately 3,000 hcc patients have been treated with lenvima since approval of this indication.

 

*1 overall survival (os): the time period from the commencement of cancer treatment up until death by any cause. whether the cause of death is cancer or not is not taken into consideration for this variable.
*2 progression free survival (pfs): pfs is the objectively confirmed time from the commencement of cancer treatment to the date of disease progression, or date of death from any cause, whichever occurs first.
*3 time to progression: ttp is the objectively confirmed time from the commencement of cancer treatment to the date of disease progression. unlike pfs, ttp does not consider death from any cause.
*4 objective response rate (orr): orr is the combined proportion of patients whose tumor was eliminated (complete response) and whose tumor was reduced by over 30% in size (partial response) as verified by imaging assessment.

 

 

contacts
 

 

eisai public relations
81-(0)3-3817-5120

eisai investor relations
81-(0)3-3817-3016

 

 

merck media relations
pamela eisele: (267) 305-3558
ann bush: (908) 740-6677

merck investor relations
teri loxam: (908) 740-1986
michael decarbo: (908) 740-1807

 

– notes for editors –

about the reflect trial (study 304) 2

reflect was a large (n=954) phase 3, randomized, multicenter, open-label trial conducted by eisai to compare the efficacy and safety of lenvima versus sorafenib as a first-line systemic treatment in patients with unresectable hcc. patients at 154 trial sites in 20 countries were randomized to receive lenvima  12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg, respectively) (n=478) or sorafenib 400 mg twice a day (n=476). treatment was continued until disease progression or unacceptable toxicity. the primary endpoint of this study was os, tested first for non-inferiority to sorafenib, then for superiority. the key secondary efficacy endpoints of this study included pfs, ttp and orr, tested for superiority to sorafenib.

in the china package insert, reflect showed that lenvima achieved the primary endpoint, demonstrating a treatment effect on os by statistical confirmation of non-inferiority to sorafenib. patients treated with lenvima experienced a median os of 13.6 months compared to 12.3 months with sorafenib (hazard ratio [hr]: 0.92; 95% confidence interval [ci]: 0.79-1.06). patients randomized to the lenvima arm did not have a statistically significant improvement in os compared to those in the sorafenib arm. in addition, lenvima showed statistically significant superiority and clinically meaningful improvements in the secondary efficacy endpoints of pfs, ttp and orr, as confirmed by a blinded independent imaging review:

  • median pfs was doubled with lenvima compared to sorafenib: 7.3 months versus 3.6 months (hr: 0.64; 95% ci: 0.55–0.75; p<0.00001) per blinded independent imaging review based on mrecist criteria.
  • median ttp was doubled with lenvima compared to sorafenib: 7.4 months versus 3.7 months (hr: 0.60; 95% ci: 0.51–0.71; p<0.00001) per blinded independent imaging review based on mrecist criteria.
  • lenvima showed nearly 3.5 times the orr of sorafenib: 40.6% (95% ci: 36.2-45.0) versus 12.4% (95% ci: 9.4-15.4) per blinded independent imaging review based on mrecist criteria (odds ratio 5.01, 95% ci: 3.59-7.01; p<0.00001).

 
about the subpopulation analysis of patients from the greater chinese region3

the results of subpopulation analysis of patients from the greater chinese region3were based on 288 patients out of the 954 hcc patients who participated in the reflect study. in this subpopulation analysis, median os was 15.0 months for lenvima versus 10.2 months for sorafenib (hr: 0.73; 95% ci: 0.55-0.96; nominal p=0.02620). independent imaging review based on mrecist criteria revealed the following results: pfs (lenvima 8.4 months versus sorafenib 3.6 months in median [hr: 0.47; 95% ci: 0.35-0.64; nominal p<0.00001]), ttp (lenvima 9.2 months versus sorafenib 3.6 months in median [hr: 0.45; 95% ci: 0.33-0.62; nominal p<0.00001]) and orr (lenvima 43.8% versus sorafenib 13.2% [odds ratio 5.14; 95% ci: 2.84-9.31; nominal p<0.00001]).

additionally, of the 288 patients in the subpopulation, approximately 80% (n=242) were living with hcc resulting from hbv. an analysis of these patients revealed the following results for os: lenvima (n=123) 14.9 months versus sorafenib (n=119) 9.9 months in median (hr: 0.72; 95% ci: 0.53-0.97).


about unresectable hepatocellular carcinoma (hcc) 

liver cancer is the second leading cause of cancer-related deaths and is estimated to be responsible for 750,000 deaths per year globally. additionally, 780,000 cases are newly diagnosed each year.2 there is a large regional difference, with about 80% of new cases occurring in asian regions, including china and japan. hcc accounts for 85% to 90% of primary liver cancer cases. hcc is associated with chronic liver disease, in particular cirrhosis. major causes of cirrhosis include hepatitis b virus and hepatitis c virus. however, according to a recent investigation, non-b/non-c hcc is on the rise. surgery is the first option for treatment, but for patients with unresectable hcc who are not amenable for potentially curative therapeutic interventions, which include liver transplant, surgical resection and tumor ablation (typically radiofrequency ablation or cryotherapy), or who are not suitable for transarterial chemoembolization (tace), treatment options are limited and the prognosis is very poor.

 

about lenvima® (lenvatinib mesylate) 

discovered and developed in-house by eisai, lenvima is an orally administered kinase inhibitor with a novel binding mode that selectively inhibits the multi activities of vascular endothelial growth factor (vegf) receptors (vegfr1, vegfr2 and vegfr3) and fibroblast growth factor (fgf) receptors (fgfr1, fgfr2, fgfr3 and fgfr4) in addition to other pathway-related rtks (including the platelet-derived growth factor (pdgf) receptor pdgfrα; kit; and ret) involved in tumor angiogenesis, tumor progression and modification of tumor immunity.

currently, eisai has obtained approval for lenvima as a treatment for refractory thyroid cancer in over 50 countries, including the united states, japan, in europe and asia. additionally, eisai has obtained approval for the agent in combination with everolimus as a second-line treatment for rcc in over 45 countries, including the united states and in europe. in europe, the agent was launched under the brand name kisplyx® for rcc.

in addition, lenvima has been approved as a treatment for hepatocellular carcinoma in japan, the united states, europe and south korea. eisai has submitted applications for an indication covering hepatocellular carcinoma in chinese taiwan (december 2017), as well as in other countries.

it is important to note that the dose for lenvima for patients with unresectable hcc is based on the patient’s weight (12 mg for patients weighing 60 kilograms or more, 8 mg for patients weighing less than 60 kilograms); the recommended dosage and dose adjustments are described in the full prescribing information.

 

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

in march 2018, eisai and merck & co., inc., kenilworth, n.j., u.s.a, 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 and commercialize lenvima, both as monotherapy and in combination with merck & co., inc., kenilworth, n.j., u.s.a.’s anti-pd-1 therapy keytruda®(pembrolizumab). in addition to ongoing clinical studies of the combination, the companies will jointly initiate new clinical studies evaluating the lenvima and keytruda combination to support 11 potential indications in six types of cancer, as well as a basket trial targeting six additional cancer types. the lenvima and keytruda combination is not approved in any cancer types today.

 

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 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 human health care philosophy by delivering innovative products in various therapeutic areas with high unmet medical needs, including oncology and neurology.

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 

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 a century, merck & co., inc., kenilworth, n.j., u.s.a., a leading global biopharmaceutical company 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. through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. we also demonstrate our commitment to 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 advance the prevention and treatment of diseases that threaten people and communities around the world – including cancer, cardio-metabolic diseases, emerging animal diseases, alzheimer’s disease and infectious diseases including hiv and ebola.

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 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 2017 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 ().

keytruda® is a registered trademark of merck sharp & dohme corp., a subsidiary of merck & co., inc., kenilworth, n.j., u.s.a.

1 globocan2012: estimated cancer incidence, mortality and prevalence worldwide in 2012. .
2 kudo m et al., “lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial” the lancet 2018, 391 (10126), 1163-1173
3 the package insert of lenvatinib mesilate capsules in china

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that its south korea subsidiary eisai korea inc. received approval for the kinase inhibitor lenvima® (lenvatinib mesylate) as a single agent for the first-line treatment of patients with unresectable hepatocellular carcinoma (hcc) from the ministry of food and drug safety (mfds) in south korea. an application seeking approval of lenvima for use in the treatment of unresectable hcc was submitted in south korea in march 2018. this approval for lenvima in south korea marks the second in asia following approval in japan. lenvima is the first new treatment option approved in ten years as a first-line systemic treatment for hcc in south korea.
in march 2018, eisai and merck & co., inc., kenilworth, n.j., u.s.a, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvima. the companies are expected to commence co-commercialization efforts for lenvima in south korea by the end of 2018.

this approval was based on results from reflect (study 304), an open-label, phase iii trial where lenvima demonstrated a treatment effect on overall survival (os)*1 by statistical confirmation of non-inferiority when compared with the standard of care, sorafenib, in 954 patients with previously untreated unresectable hcc. lenvima also demonstrated statistically significant superiority and clinically meaningful improvements in progression-free survival (pfs)*2 and objective response rate (orr)*3.

reflect showed that lenvima achieved the primary endpoint, demonstrating a treatment effect on os by statistical confirmation of non-inferiority to sorafenib. patients treated with lenvima experienced a median os of 13.6 months compared to 12.3 months with sorafenib (hazard ratio [hr]: 0.92; 95% confidence interval [ci]: 0.79-1.06). the os analysis was conducted as prespecified in the statistical analysis plan when 351 events had occurred in the lenvima arm and 350 events had occurred in the sorafenib arm. regarding secondary efficacy endpoints, according to independent imaging review based on mrecist criteria, lenvima showed statistically significant superiority and clinically meaningful improvements as compared to sorafenib in median pfs: lenvima 7.3 months versus sorafenib 3.6 months (hr: 0.64; 95% ci: 0.55-0.75; p<0.0001) and orr: lenvima 40.6% versus sorafenib 12.4% (p<0.0001). the five most common adverse reactions observed in patients treated with lenvima were hypertension, diarrhea, decreased appetite, weight loss and fatigue, which is consistent with the known side-effect profile of lenvima.

liver cancer is the second leading cause of cancer related deaths and is estimated to be responsible for approximately 750,000 deaths per year globally. additionally, approximately 780,000 cases are newly diagnosed each year, about 80% of which occur in asian regions.1 hcc accounts for 85% to 90% of primary liver cancer cases. unresectable hcc, for which treatment options are limited, is extremely difficult to treat, and the development of new treatments is necessary.

lenvima has been approved as a treatment for refractory thyroid cancer in over 50 countries including the united states, japan, in europe and asia, and as combination with everolimus as a second-line treatment for rcc in over 45 countries including the united states and in europe.

since the initial launch, more than 10,000 patients have been treated with lenvima, which is approved in more than 50 countries worldwide. in japan, approximately 3,000 hcc patients have been treated with lenvima since the approval of the hcc indication in march 2018.

eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. eisai is committed to exploring the potential clinical benefits of lenvima, in collaboration with merck & co., inc., kenilworth, n.j., u.s.a., as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to cancer patients, their families, and healthcare providers worldwide.

 

*1 overall survival (os): the time period from the commencement of cancer treatment up until death by any cause. whether the cause of death is cancer or not is not taken into consideration for this variable.

*2 progression free survival (pfs): pfs is the objectively confirmed time from the commencement of cancer treatment to the date of disease progression, or date of death from any cause, whichever occurs first.

*3 objective response rate (orr): orr is the combined proportion of patients whose tumor was eliminated (complete response) and whose tumor was reduced by over 30% in size (partial response) as verified by imaging assessment.

 

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

 

[notes to editors]
1. about lenvima® (lenvatinib mesylate)
discovered and developed in-house by eisai, lenvima is an orally administered kinase inhibitor with a novel binding mode that selectively inhibits the multi activities of vascular endothelial growth factor (vegf) receptors (vegfr1, vegfr2 and vegfr3) and fibroblast growth factor (fgf) receptors (fgfr1, fgfr2, fgfr3 and fgfr4) in addition to other pathway-related rtks (including the platelet-derived growth factor (pdgf) receptor pdgfrα; kit; and ret) involved in tumor angiogenesis, tumor progression and modification of tumor immunity.

currently, eisai has obtained approval for lenvima as a treatment for refractory thyroid cancer in over 50 countries, including the united states, japan, in europe and asia. additionally, eisai has obtained approval for the agent in combination with everolimus as a second-line treatment for rcc in over 45 countries, including the united states and in europe. in europe, the agent was launched under the brand name kisplyx® for rcc.

in addition, lenvima has been approved as a treatment for hepatocellular carcinoma in japan, the united states and europe. eisai has submitted applications for an indication covering hepatocellular carcinoma in china (october 2017, designated for priority review and approval in december 2017), chinese taiwan (december 2017), and other countries.

it is important to note that the dose for lenvima for patients with unresectable hcc is based on the patient’s weight (12 mg for patients weighing 60 kilograms or more, 8 mg for patients weighing less than 60 kilograms); the recommended dosage and dose adjustments are described in the full prescribing information.

 

2. about the eisai and merck & co., inc., kenilworth, n.j., u.s.a. strategic collaboration
in march 2018, eisai and merck & co., inc., kenilworth, n.j., u.s.a, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvima (lenvatinib). under the agreement, the companies will jointly develop and commercialize lenvima, both as monotherapy and in combination with merck & co., inc., kenilworth, n.j., u.s.a.’s anti-pd-1 therapy keytruda® (pembrolizumab). in addition to ongoing clinical studies of the combination, the companies will jointly initiate new clinical studies evaluating the lenvima and keytruda combination to support 11 potential indications in six types of cancer, as well as a basket trial targeting six additional cancer types.

 

3. about the reflect trial (study 304) 
reflect was a large (n=954) phase iii, randomized, multicenter, open-label trial conducted by eisai to compare the efficacy and safety of lenvatinib versus sorafenib as a first-line systemic treatment in patients with unresectable hepatocellular carcinoma (hcc). patients at 154 trial sites in 20 countries were randomized to receive lenvatinib 12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg, respectively) (n=478) or sorafenib 400 mg twice a day (n=476). treatment was continued until disease progression or unacceptable toxicity. the primary endpoint of this study was overall survival, tested first for non-inferiority to sorafenib, then for superiority. reflect showed that lenvima achieved the primary endpoint, demonstrating a treatment effect on os by statistical confirmation of non-inferiority to sorafenib. patients treated with lenvima experienced a median os of 13.6 months compared to 12.3 months with sorafenib (hazard ratio [hr]: 0.92; 95% confidence interval [ci]: 0.79-1.06).

in addition, lenvima showed statistically significant superiority and clinically meaningful improvements in the secondary efficacy endpoints of pfs and orr, as confirmed by a blinded independent imaging review (iir).

median pfs was doubled with lenvima compared to sorafenib: 7.3 months versus 3.6 months (hr: 0.64; 95% ci: 0.55–0.75; p<0.0001) per blinded independent imaging review based on mrecist criteria, and 7.3 months with lenvima versus 3.6 months with sorafenib (hr: 0.65; 95% ci: 0.56–0.77) per recist 1.1. lenvima showed nearly 3.5 times the orr of sorafenib: 40.6% (95% ci: 36.2-45.0) (complete response [cr]=2% (n=10), partial response [pr]=38% (n=184)) vs. 12.4% (95% ci: 9.4-15.4) (cr=1% (n=4), pr=12% (n=55)) per blinded independent imaging review based on mrecist criteria, respectively (p<0.0001), and 18.8% (95% ci: 15.3-22.3) with lenvima versus 6.5% (95% ci: 4.3-8.7) with sorafenib per recist 1.1.

in addition, median time to progression (ttp) was doubled with lenvima compared to sorafenib: 7.4 months versus 3.7 months (hr: 0.60; 95% ci: 0.51-0.71; p<0.0001) per blinded independent imaging review based on mrecist criteria, and 7.4 months with lenvima versus 3.7 months with sorafenib (hr: 0.61; 95% ci: 0.51-0.72; p<0.0001) per recist 1.1.

the results of the reflect trial were published in the lancet 2018, 391 (10126), 1163-1173 (published online on february 9, 2018).

 

4. about unresectable hepatocellular carcinoma (hcc)
liver cancer is the second leading cause of cancer related deaths and is estimated to be responsible for 750,000 deaths per year globally. additionally, 780,000 cases are newly diagnosed each year. there is a large regional difference, with about 80% of new cases occurring in asian regions, including china and japan.1 hcc accounts for 85% to 90% of primary liver cancer cases. hcc is associated with chronic liver disease, in particular cirrhosis. major causes of cirrhosis include hepatitis b virus and hepatitis c virus. however, according to a recent investigation, non-b/non-c hcc is on the rise. surgery is the first option for treatment, but for patients with unresectable hcc who are not amenable for potentially curative therapeutic interventions, which include liver transplant, surgical resection, and tumor ablation (typically radiofrequency ablation or cryotherapy), or who are not suitable for transarterial chemoembolization (tace), treatment options are limited and the prognosis is very poor.

 

1 globocan2012: estimated cancer incidence, mortality and prevalence worldwide in 2012. http://globocan.iarc.fr/

keytruda® is a registered trademark of merck sharp & dohme corp., a subsidiary of merck & co., inc., kenilworth, n.j., u.s.a.

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