news – page 10 – eisai china lnc.-pg电子app

tokyo and new york, june 18, 2021 — eisai co., ltd. and bristol-myers squibb company (nyse: bmy) announced today that the companies have entered into an exclusive global strategic collaboration agreement for the co-development and co-commercialization of morab-202, an antibody drug conjugate (adc). morab-202 is eisai’s first adc and combines eisai’s in house developed anti-folate receptor alpha (frα) antibody, and eisai’s anticancer agent eribulin, using an enzyme cleavable linker. it is a potential best-in-class frα adc with a favorable pharmacology profile and demonstrated single agent activity in patients with advanced solid tumors. eisai is currently investigating morab-202 in frα-positive solid tumors (inclusive of endometrial, ovarian, lung and breast cancers) in two studies: a phase 1 clinical study in japan and a phase 1/2 clinical study in the united states. the companies are planning to move into the registrational stage of development for this asset as early as next year.

under the agreement, eisai and bristol myers squibb will jointly develop and commercialize morab-202 in the following collaboration territories: japan; china; countries in the asia-pacific region*; the united states; canada; europe, including the european union and the united kingdom; and russia. bristol myers squibb will be solely responsible for developing and commercializing the drug in regions outside of the collaboration territories. eisai will remain responsible for the manufacturing and supply of morab-202 globally.

under the financial terms of the agreement, bristol myers squibb will pay $650 million u.s. dollars to eisai including $200 million u.s. dollars as payment toward eisai research and development expenses. eisai is also entitled to receive up to $2.45 billion u.s. dollars in potential future development, regulatory, and commercial milestones. the parties will share profits, research and development and commercialization costs in the collaboration territories and bristol myers squibb will pay eisai a royalty on sales outside of the collaboration territories. eisai is expected to book sales of morab-202 in japan, china, countries in the asia-pacific region, europe and russia. bristol myers squibb is expected to book sales of morab-202 in the united states and canada.

“morab-202 combines eisai’s in-house discovered antibody and payload using the company’s advanced chemistry capabilities.” said haruo naito, chief executive officer at eisai. “it is characterized by its payload of eribulin, which is a product of our modern synthetic organic chemistry that has already made contributions to patients with breast cancer and soft tissue sarcoma. our collaboration with bristol myers squibb will accelerate the development of morab-202 with the goal of bringing a potentially impactful treatment option to patients globally.”

“this global collaboration with eisai is an important strategic fit for bristol myers squibb as it extends our leading position in oncology with a differentiated asset that complements our broad solid tumor portfolio and leverages our deep internal development expertise.” said giovanni caforio, m.d., board chair and chief executive officer, bristol myers squibb. “we look forward to collaborating with eisai as we work to bring this potential treatment option to patients in need as soon as possible.”

 

applications based on progression-free survival, overall survival, and objective response rate data from respective pivotal phase 3 trials

 

tokyo and kenilworth, n.j., may 6, 2021 – eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) and merck & co., inc., kenilworth, n.j., u.s.a. (known as msd outside the united states and canada) today announced that the u.s. food and drug administration (fda) has accepted and granted priority review for applications seeking two new approvals for the combination of lenvima, the orally available multiple receptor tyrosine kinase inhibitor discovered by eisai, plus keytruda, the anti-pd-1 therapy from merck & co., inc., kenilworth, n.j., u.s.a. the first set of applications (a supplemental new drug application [snda] for lenvima and a supplemental biologics license application [sbla] for keytruda) are for the first-line treatment of patients with advanced renal cell carcinoma (rcc), based on progression-free survival (pfs), overall survival (os) and objective response rate (orr) data from the pivotal phase 3 clear study (study 307/keynote-581). the second set of applications are for the treatment of patients with advanced endometrial carcinoma who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation, based on pfs, os, and orr data from the pivotal phase 3 study 309/keynote-775 trial. these are the first applications to be submitted in the u.s. for this combination therapy based on phase 3 clinical data. the fda has set prescription drug user fee act (pdufa) dates, or target action dates, of august 25 and 26, 2021, for the advanced rcc snda and sbla applications, respectively, and september 3, 2021, for the advanced endometrial carcinoma applications.

“advanced renal cell carcinoma and advanced endometrial carcinoma are aggressive cancers, and patients urgently need new treatment options that may help improve outcomes,” said dr. gregory lubiniecki, vice president, oncology clinical research, merck & co., inc., kenilworth, n.j., u.s.a. research laboratories. “we appreciate that the fda has recognized this significant unmet need and the potential for the combination of keytruda plus lenvima in these patients by granting priority review for these applications.”

“we are pleased that the fda has granted priority review for lenvima plus keytruda—both in advanced renal cell carcinoma and advanced endometrial carcinoma— underscoring the potential significance of the outcomes observed in the clear study (study 307/keynote-581) and study 309/keynote-775 trials,” said dr. takashi owa, chief medicine creation officer and chief discovery officer, oncology business group at eisai. “many patients are still in need of new and effective therapies, which fuels our commitment to advancing the development of this combination even more. these milestones reinforce our unwavering dedication to helping the patients we aim to serve.”

the applications in advanced rcc are based on results from the clear study (study 307/keynote-581), in which lenvima plus keytruda demonstrated statistically significant improvements in pfs, os and orr versus sunitinib. these data were presented in february at the virtual 2021 genitourinary cancers symposium (asco gu) and simultaneously published in the new england journal of medicine. ¹

the applications in advanced endometrial carcinoma are based on results from study 309/keynote-775, in which lenvima plus keytruda demonstrated statistically significant improvements in pfs, os and orr versus chemotherapy (investigator’s choice of doxorubicin or paclitaxel), regardless of mismatch repair (mmr) status. these data were presented in march at the virtual society of gynecologic oncology (sgo) 2021 annual meeting on women’s cancer. study 309/keynote-775 is the confirmatory trial for study 111/keynote-146, which supported the 2019 accelerated approval of the combination for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (msi-h) or mismatch repair deficient (dmmr), who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation. this indication was an accelerated approval based on tumor response and durability of response and reviewed under the fda’s real-time oncology review pilot program and the fda’s project orbis. continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.

eisai and merck & co., inc., kenilworth, n.j., u.s.a. are studying the lenvima plus keytruda combination through the leap (lenvatinib and pembrolizumab) clinical program in 14 different tumor types (endometrial carcinoma, hepatocellular carcinoma, melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, urothelial cancer, biliary tract cancer, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer, pancreatic cancer and triple-negative breast cancer) across more than 20 clinical trials.

 

about lenvima^® (lenvatinib) capsules

lenvima, discovered and developed by eisai, is an orally available kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (vegf) receptors vegfr1 (flt1), vegfr2 (kdr), and vegfr3 (flt4). lenvima inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (fgf) receptors fgfr1-4, the platelet derived growth factor receptor alpha (pdgfrα), kit, and ret. in syngeneic mouse tumor models, lenvima decreased tumor-associated macrophages, increased activated cytotoxic t cells, and demonstrated greater antitumor activity in combination with an anti-pd-1 monoclonal antibody compared to either treatment alone.

currently, lenvima has been approved for monotherapy as a treatment for thyroid cancer in over 70 countries including japan, in europe, china and in asia, and in the united states for radioiodine-refractory differentiated thyroid cancer. in addition, lenvima has been approved for monotherapy as a treatment for unresectable hepatocellular carcinoma in over 70 countries including japan, the united states, in europe, china and in asia. it is also approved in combination with everolimus as a treatment for renal cell carcinoma following prior antiangiogenic therapy in over 60 countries, including the united states, in europe and asia. in europe, the agent was launched under the brand name kisplyx^® for renal cell carcinoma. in addition, it is approved in combination with keytruda (generic name: pembrolizumab) as a treatment for advanced endometrial carcinoma that is not microsatellite instability-high (msi-h) or mismatch repair deficient (dmmr) who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation in over 10 countries including the united states, canada and australia. continued approval for this indication is contingent upon verification and description of clinical benefit in the confirmatory trials. lenvima has also been approved for monotherapy as a treatment for unresectable thymic carcinoma in japan.

 

about keytruda^® (pembrolizumab) injection, 100mg

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

merck & co., inc., kenilworth, n.j., u.s.a. has the industry’s largest immuno-oncology clinical research program. there are currently more than 1,400 trials studying keytruda across a wide variety of cancers and treatment settings. the keytruda clinical program seeks to understand the role of keytruda across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with keytruda, including exploring several different biomarkers.

 

about clear study (study 307/keynote-581)

the clear study (study 307/keynote-581) is a multicenter, randomized, open-label, phase 3 trial (clinicaltrials.gov, ) evaluating lenvima in combination with keytruda or in combination with everolimus versus sunitinib for the first-line treatment of patients with advanced rcc. the primary endpoint is pfs, as assessed by independent review per response evaluation criteria in solid tumors (recist) v1.1. key secondary endpoints include os, orr and safety. a total of 1,069 patients were randomized (1:1:1) to receive lenvima (20 mg orally once daily) in combination with keytruda (200 mg intravenously [iv] every three weeks for up to 24 months); or lenvima (18 mg orally once daily) in combination with everolimus (5 mg orally once daily); or sunitinib (50 mg orally once daily for four weeks on treatment, followed by two weeks off treatment).

in the trial’s primary endpoint of pfs, as assessed by independent review per recist v1.1, lenvima plus keytruda reduced the risk of disease progression or death by 61% (hr=0.39 [95% ci: 0.32-0.49]; p<0.001), with a median pfs of 23.9 months (95% ci: 20.8-27.7) versus 9.2 months (95% ci: 6.0-11.0) for patients who received sunitinib. in the trial’s key secondary endpoints, lenvima plus keytruda reduced the risk of death by 34% (hr=0.66 [95% ci: 0.49-0.88]; p=0.005) versus patients who received sunitinib. median os was not reached in either treatment arm after a median follow-up of 27 months. treatment with lenvima plus keytruda resulted in an orr of 71.0% (95% ci: 66.3-75.7), with a complete response (cr) rate of 16.1% and a partial response (pr) rate of 54.9%, versus an orr of 36.1% (95% ci: 31.2-41.1), with a cr rate of 4.2% and a pr rate of 31.9%, for patients who received sunitinib (relative risk=1.97 [95% ci: 1.69-2.29]). median duration of response (dor) for patients who received lenvima plus keytruda was 25.8 months (95% ci: 22.1-27.9) versus 14.6 months (95% ci: 9.4-16.7) for patients who received sunitinib.

in the lenvima plus keytruda arm, treatment-related adverse events (traes) led to discontinuation of lenvima in 18.5% of patients, of keytruda in 25.0% of patients, and of both in 9.7% of patients. in the sunitinib arm, traes led to discontinuation of sunitinib in 10.0% of patients. grade 5 traes occurred in 1.1% of patients in the lenvima plus keytruda arm versus 0.3% of patients in the sunitinib arm. grade ≥3 traes occurred in 71.6% of patients in the lenvima plus keytruda arm versus 58.8% of patients in the sunitinib arm. the most common traes of any grade occurring in at least 20% of patients in the lenvima plus keytruda arm were diarrhea (54.5%), hypertension (52.3%), hypothyroidism (42.6%), decreased appetite (34.9%), fatigue (32.1%) and stomatitis (32.1%). in the sunitinib arm, the most common traes of any grade occurring in at least 20% of patients were diarrhea (44.4%), hypertension (39.1%), stomatitis (37.4%), hand-foot syndrome (35.9%), fatigue (32.1%) and nausea (27.6%).

 

about study 309/keynote-775

study 309/keynote-775 is a multicenter, randomized, open-label, phase 3 trial (clinicaltrials.gov, ) evaluating lenvima in combination with keytruda in patients with advanced endometrial carcinoma who had been previously treated with at least one prior platinum-based chemotherapy regimen in any setting, including in the neoadjuvant and adjuvant settings. the dual primary endpoints are pfs, as assessed by blinded independent central review (bicr) per recist v1.1, and os. select secondary endpoints include orr and duration of response (dor), as assessed by bicr. a total of 827 patients were randomized (1:1) to receive lenvima (20 mg orally once daily) in combination with keytruda (200 mg iv every three weeks); or investigator’s choice of either doxorubicin (60 mg/m² iv every three weeks) or paclitaxel (80 mg/m² iv on a 28-day cycle, three weeks of receiving weekly paclitaxel and one week of not receiving paclitaxel).

the study met the dual primary endpoints of pfs, as assessed by bicr per recist v1.1, os, as well as the secondary efficacy endpoint of orr, as assessed by bicr per recist v1.1, in the all-comer population (pmmr and dmmr) and in the pmmr subgroup. median follow-up was 11.4 months for both the all-comer population and pmmr subgroup. a statistically significant improvement in pfs was seen in the all-comer population, in which lenvima plus keytruda (n=411) reduced the risk of disease progression or death by 44% (hr=0.56 [95% ci: 0.47-0.66]; p<0.0001), with a median pfs of 7.2 months (95% ci: 5.7-7.6; number of events=281) versus 3.8 months (95% ci: 3.6-4.2; number of events=286) for patients who received tpc (n=416). additionally, a statistically significant improvement in os was seen in the all-comer population, in which lenvima plus keytruda reduced the risk of death by 38% (hr=0.62 [95% ci: 0.51-0.75]; p<0.0001), with a median os of 18.3 months (95% ci: 15.2-20.5; number of events=188) versus 11.4 months (95% ci: 10.5-12.9; number of events=245) for patients who received tpc. the safety profile of lenvima plus keytruda was generally consistent with the established safety profiles of the individual monotherapies.

in the all-comer population, the secondary efficacy endpoint of orr was 31.9% (95% ci: 27.4-36.6), with a cr rate of 6.6% and a pr rate of 25.3%, for patients who received lenvima plus keytruda versus 14.7% (95% ci: 11.4-18.4), with a cr rate of 2.6% and a pr rate of 12.0% for patients who received tpc (orr difference versus tpc: 17.2 percentage points; p<0.0001). for patients who responded, the median duration of response (dor) was 14.4 months (range: 1.6-23.7) for patients who received lenvima plus keytruda versus 5.7 months (range: 0.0-24.2) for patients who received tpc.

results were similar across the all-comer population and the pmmr subgroup. in the pmmr subgroup, lenvima plus keytruda reduced the risk of disease progression or death by 40% (hr=0.60 [95% ci: 0.50-0.72]; p<0.0001), with a median pfs of 6.6 months (95% ci: 5.6-7.4; number of events=247) versus 3.8 months (95% ci: 3.6-5.0; number of events=238) for patients who received tpc. lenvima plus keytruda reduced the risk of death by 32% (hr=0.68 [95% ci: 0.56-0.84]; p =0.0001), with a median os of 17.4 months (95% ci: 14.2-19.9; number of events=165) versus 12.0 months (95% ci: 10.8-13.3; number of events=203) for patients who received tpc. the secondary endpoint of orr was 30.3% (95% ci: 25.5-35.5), with a cr rate of 5.2% and a pr rate of 25.1%, for patients who received lenvima plus keytruda versus 15.1% (95% ci: 11.5-19.3), with a cr rate of 2.6% and a pr rate of 12.5%, for patients who received tpc (orr difference versus tpc: 15.2 percentage points: p<0.0001). for patients who responded, the median dor was 9.2 months (range: 1.6-23.7) for patients who received lenvima plus keytruda versus 5.7 months (range: 0.0-24.2) for patients who received tpc.

in the all-comer population, in the lenvima plus keytruda arm (n=406), any grade treatment-emergent adverse events (teaes) led to discontinuation of lenvima in 30.8% of patients, of keytruda in 18.7% of patients, and of both in 14.0% of patients. in the tpc arm (n=388), any grade teaes led to discontinuation of chemotherapy in 8.0% of patients. grade 5 teaes of any cause occurred in 5.7% of patients in the lenvima plus keytruda arm and in 4.9% of patients in the tpc arm. grade ≥3 teaes occurred in 88.9% of patients in the lenvima plus keytruda arm and in 72.7% of patients in the tpc arm. in the lenvima plus keytruda arm, the most common teaes of any grade occurring in at least 25% of patients were hypertension (64.0%), hypothyroidism (57.4%), diarrhea (54.2%), nausea (49.5%), decreased appetite (44.8%), vomiting (36.7%), weight decrease (34.0%), fatigue (33.0%), arthralgia (30.5%), proteinuria (28.8%), anemia (26.1%), constipation (25.9%), and urinary tract infection (25.6%). in the tpc arm, the most common teaes of any grade occurring in at least 25% of patients were anemia (48.7%), nausea (46.1%), neutropenia (33.8%), alopecia (30.9%), and fatigue (27.6%). median treatment duration was 231 days (range: 1-817) with lenvima plus keytruda and 104.5 days (range: 1-785) with tpc.

 

about renal cell carcinoma (rcc)^2,3,4,5,6,7

worldwide, it is estimated there were more than 431,000 new cases of kidney cancer diagnosed and more than 179,000 deaths from the disease in 2020. in japan, there were more than 25,000 new cases and 8,000 deaths in 2020. in the u.s. alone, it is estimated there will be more than 76,000 new cases of kidney cancer diagnosed and almost 14,000 deaths from the disease in 2021. renal cell carcinoma is by far the most common type of kidney cancer; about nine out of 10 kidney cancers are rccs. renal cell carcinoma is about twice as common in men as in women. most cases of rcc are discovered incidentally during imaging tests for other abdominal diseases. approximately 30% of patients with rcc will have metastatic disease at diagnosis, and as many as 40% will develop metastases after primary surgical treatment for localized rcc. survival is highly dependent on the stage at diagnosis, and the five-year survival rate is 13% for patients with metastatic disease.

 

about endometrial carcinom^8,9,10,11,12

endometrial carcinoma begins in the inner lining of the uterus, which is known as the endometrium, and is the most common type of cancer in the uterus. in 2020, it was estimated there were more than 417,000 new cases and more than 97,000 deaths from uterine body cancers worldwide (these estimates include both endometrial cancers and uterine sarcomas; more than 90% of uterine body cancers occur in the endometrium, so the actual numbers for endometrial cancer cases and deaths are slightly lower than these estimates). in japan, there were more than 17,000 new cases of uterine body cancer and more than 3,000 deaths from the disease in 2020. in the u.s., it is estimated there will be more than 66,000 new cases of uterine body cancer and nearly 13,000 deaths from the disease in 2021. the five-year survival rate for metastatic endometrial cancer (stage iv) is estimated to be approximately 17%.

 

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

in march 2018, eisai and merck & co., inc., kenilworth, n.j., u.s.a., known as msd outside the united states and canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvima. under the agreement, the companies will jointly develop, manufacture and commercialize lenvima, both as monotherapy and in combination with keytruda, the anti-pd-1 therapy from merck & co., inc., kenilworth, n.j., u.s.a.

in addition to ongoing clinical studies evaluating the lenvima plus keytruda combination across several different tumor types, the companies have jointly initiated new clinical studies through the leap (lenvatinib and pembrolizumab) clinical program and are evaluating the combination in 14 different tumor types (endometrial carcinoma, hepatocellular carcinoma, melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, urothelial cancer, biliary tract cancer, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer, pancreatic cancer and triple-negative breast cancer) across more than 20 clinical trials.

 

eisai’s focus on cancer

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

 

about eisai

eisai is a leading global research and development-based pharmaceutical company headquartered in japan, with approximately 10,000 employees worldwide. we define our corporate mission as “giving first thought to patients and their families and to increasing the benefits health care provides,” which we call our human health care (hhc) philosophy. we strive to realize our hhc philosophy by delivering innovative products in therapeutic areas with high unmet medical needs, including oncology and neurology. in the spirit of hhc, we take that commitment even further by applying our scientific expertise, clinical capabilities and patient insights to discover and develop innovative solutions that help address society’s toughest unmet needs, including neglected tropical diseases and the sustainable development goals.

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

 

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

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

 

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

for 130 years, merck & co., inc., kenilworth, n.j., u.s.a., known as msd outside of the united states and canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. we demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. today, merck & co., inc., kenilworth, n.j., u.s.a. continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as hiv and ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. for more information, visit and connect with us on , , , and .

 

forward-looking statement of merck & co., inc., kenilworth, n.j., usa

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

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

the company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2020 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 ().

 

¹ motzer r. et al. lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma.  the new england journal of medicine

²  international agency for research on cancer, world health organization. “kidney fact sheet.” cancer today, 2020.

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³  international agency for research on cancer, world health organization. “japan fact sheet.” cancer today, 2020.
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⁴  american cancer society. key statistics about kidney cancer,
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⁵  thomas a. z. et al. the role of metastasectomy in patients with renal cell carcinoma with sarcomatoid dedifferentiation: a matched controlled analysis. the journal of urology. 2016 sep; 196(3): 678–684.
.

⁶  shinder b. et al. surgical management of advanced and metastatic renal cell carcinoma: a multidisciplinary approach. frontiers in oncology. 2017; 7: 107. .

⁷  padala, s. a., barsouk, a., thandra, k. c., saginala, k., mohammed, a., vakiti, a., rawla, p., & barsouk, a. (2020). epidemiology of renal cell carcinoma. world journal of oncology, 11(3), 79–87. .

⁸ american cancer society, facts & figures 2020 pdf:

⁹ international agency for research on cancer, world health organization. “corpus uteri fact sheet.” cancer today, 2020.

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¹⁰ international agency for research on cancer, world health organization. “japan fact sheet.” cancer today, 2020.

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¹¹ cancer research institute website, accessed 3/1/2021:

¹² american cancer society website, accessed 3/1/2021:

kyorin pharmaceutical co., ltd. (headquarters: chiyoda-ku, tokyo, president and ceo: shigeru ogihara, “kyorin”), a subsidiary of kyorin holdings, inc. (headquarters: chiyoda-ku, tokyo, president and ceo: yutaka ogihara), and eisai co., ltd. (headquarters: bunkyo-ku, tokyo, ceo: haruo naito, “eisai”) have entered into a license agreement for development and distribution of vibegron, a therapeutic agent for overactive bladder, in four asean (association of southeast asian nations) member states; thailand, the philippines, malaysia and brunei. based on this agreement, eisai will acquire exclusive development and marketing rights from kyorin for the agent in the said four countries, and will be responsible for submitting a new drug application for the agent.

overactive bladder (oab) is the name for a group of urinary symptoms characterized by urinary urgency, usually accompanied by increased daytime frequent urination and/or nocturia, and in some cases by urge urinary incontinence. oab has a detrimental impact on patient health-related qol (quality of life), interfering with the patients’ daily life such as preventing them from going out due to anxiety that they often go to the bathroom due to oab, and reducing quality of sleep.

this agent is a novel β3-adrenergic receptor agonist administered once daily, acting selectively on β3 receptors in the bladder, relaxing the bladder to enhance urine collection, and consequently improving the symptoms of urgency, urinary frequency and urge urinary incontinence associated with oab.

kyorin has been making a contribution to improving the quality of life of patients with oab through early penetration of the agent into the japanese market. with the execution of this agreement, kyorin will now work with eisai to make the agent available in the licensed territory and promote the expansion of its business internationally.

eisai is making efforts to determine and meet the diversified needs of each market in the licensed territory, and will continue to actively expand and enrich its strategic product portfolio to match the needs of the region.

in september 2009, kyorin and eisai signed a license agreement for the development and marketing in asia of uritos® tablets (generic name: imidafenacin), a therapeutic agent for overactive bladder, discovered and developed by kyorin, and as of today eisai sells uritos in thailand, the philippines, indonesia and myanmar. by developing and commercializing vibegron in addition to uritos, the two companies will provide patients with new treatment options for oab and make further contributions to improving the quality of life and increasing benefits to patients with oab.

 

media inquiries
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tel : 81-(0)3-3525-4707                      tel : 81-(0)3-3817-5120

 

1. about kyorin pharmaceutical co., ltd.
kyorin is working to improve its presence in specific areas and create new drugs globally with the aim of becoming a pharmaceutical manufacturer whose significance is recognized by society, and that is trusted by patients and those involved in medical care. in terms of sales, kyorin is enhancing an fc (franchise customer) strategy that focuses on users, mainly in the respiratory, otolaryngology, and urology departments. in drug discovery, kyorin is developing its activities for first-in-class drug discovery, such as promoting selection and concentration, working on developing a multi-layered program, and actively exploring and installing external drug discovery themes.

for more information on kyorin pharmaceutical co., ltd., please visit https://www.kyorin-pharm.co.jp/en/.

 

2. about eisai co., ltd.

eisai co., ltd. defines our corporate mission as “giving first thought to patients and their families and to increasing the benefits health care provides,” which we call our human health care (hhc) philosophy. with approximately 10,000 employees working across our global network of r&d facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products to address unmet medical needs, with a particular focus in our strategic areas of neurology and oncology. as a global pharmaceutical company, our mission extends to patients around the world through working with key stakeholders to improve access to medicines in developing and emerging countries.

for further information on eisai co., ltd., please visit https://www.eisai.com.

 

3. about vibegron

vibegron was discovered by merck & co., kenilworth, n.j., u.s.a. (known as msd outside of the united states and canada) as a once-daily oral treatment for overactive bladder (oab), which acts selectively on the bladder’s β3-adrenergic receptor agonists. vibegron selectively acts on β3 receptors in the bladder and increases bladder capacity by enhancing the bladder-relaxing effect of noradrenaline during the urinary storage phase, resulting in the improvement of incontinence symptoms of urinary urgency, frequent urination and urge urinary incontinence with oab. kyorin has obtained exclusive rights for developing, manufacturing and marketing of this drug in japan (july 2014) and asia* (april 2017) from merck & co., inc. kenilworth, n.j., u.s.a. in japan, kyorin and kissei have jointly developed the agent locally under a co-development and co-marketing agreement entered into as of march 2016. since november 2018, the two companies have been jointly marketing it under the product name of “beova® tablets 50mg”.

*south korea, chinese taiwan, hksa, and 10 member states of asean

 

4. about overactive bladder (oab)

oab is a urological condition with trouble in pooling urine in the bladder. its predominant symptom is an urge to urinate, which is often accompanied by frequent urination and nocturia, and in some cases by urge urinary incontinence. one of the major problems of oab is the fact that patients refrain from leaving the house due to anxiety about going to the bathroom, cannot get enough sleep at night, or face limitations in their daily activities, which could lead to significantly-reduced quality of life.

in general, it is said that the total number of patients with oab increases with aging. in asia, although the actual number of patients is unknown, it has been reported among adults over the age of 18 that 29.9% of men and 34.7% of women experience some form of oab.1

1. j med assoc thai. 2007; 90 （11）: 2316-20

if approved, aducanumab would become the first treatment to meaningfully change the course of alzheimer’s disease
aducanumab is now under regulatory review in japan, europe and the united states

cambridge, mass. and tokyo, [december 10, 2020] (globe newswire) – today, biogen (nasdaq: biib) and eisai, co., ltd. (tokyo, japan) announced that biogen has submitted a japanese new drug application (j-nda) to the ministry of health, labor and welfare (mhlw) for aducanumab, an investigational therapy for alzheimer’s disease. aducanumab, an amyloid beta-targeting antibody, has been shown in clinical trials to remove amyloid beta in the brain and significantly slow clinical decline in patients with mild cognitive impairment (mci) due to alzheimer’s disease and mild alzheimer’s disease dementia.

“japan is the third market where we have applied for regulatory approval for aducanumab, and the filing represents continued progress on our commitment to bring this therapy to patients around the world,” said michel vounatsos, chief executive officer at biogen. “japan has met the challenges of a rapidly-aging population by demonstrating global leadership in setting policies that aim to increase support for alzheimer’s disease patients and caregivers. we look forward to the regulatory review of aducanumab with the hope that, if approved, it could help further manage the impact of this devastating disease.”

“as japan has the oldest population in the world, it is anticipated that the social burden of alzheimer’s disease will continue to grow,” said dr. haruo naito, chief executive officer at eisai co., ltd. “for more than 30 years, eisai has been dedicated to dementia research and development, and working with people living with alzheimer’s and their caregivers to fight this disease. the filing of the application is an important step in serving patients and their families as aducanumab may help reduce clinical decline and potentially maintain the ability to live an independent life for as long as possible. aducanumab also has the potential to help address the public health challenges our aging population faces in japan.”

the japanese regulatory authority will review the application through the standard review process. in addition to the filing in japan, aducanumab is under priority review with the u.s. food and drug administration, with a prescription drug user fee act (pdufa) action date of march 7, 2021 and is also under review with the european medicines agency.

 

about aducanumab

aducanumab (biib037) is an investigational human monoclonal antibody studied for the treatment of alzheimer’s disease. based on clinical data from patients with mild cognitive impairment due to alzheimer’s disease and mild alzheimer’s disease, aducanumab has the potential to impact underlying disease pathophysiology, slow cognitive and functional decline and provide benefits on patients’ ability to perform activities of daily living, including conducting personal finances, performing household chores, such as cleaning, shopping and doing laundry, and independently traveling out of the home. if approved, aducanumab would be the first treatment to meaningfully change the course of the disease for individuals living with alzheimer’s.

biogen licensed aducanumab from neurimmune under a collaborative development and license agreement. since october 2017 biogen and eisai co., ltd. have collaborated on the development and commercialization of aducanumab globally.

emerge and engage were phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group studies designed to evaluate the efficacy and safety of aducanumab. the primary objective of the studies was to evaluate the efficacy of monthly doses of aducanumab as compared with placebo in reducing cognitive and functional impairment as measured by changes in the clinical dementia rating-sum of boxes (cdr-sb) score. secondary objectives were to assess the effect of monthly doses of aducanumab as compared to placebo on clinical decline as measured by the mini-mental state examination (mmse), alzheimer’s disease assessment scale-cognitive subscale 13 items (adas-cog 13) and alzheimer’s disease cooperative study-activities of daily living inventory mild cognitive impairment version (adcs-adl-mci).

 

about alzheimer’s disease

alzheimer’s disease is a progressive neurological condition that impairs thinking, memory and independence, leading to premature death. the disease currently cannot be stopped, delayed or prevented and is a growing global health crisis, affecting those living with the disease and their families. according to the world health organization (who), tens of millions of people worldwide live with alzheimer’s disease, and the number will grow in the years ahead, outpacing the healthcare resources needed to manage it and costing billions of dollars.

according to the health, labor and welfare ministry, it is estimated approximately 4.6 million people live with dementia and about 4 million people live with mild cognitive impairment (mci) in japan (2012). alzheimer’s disease is suspected to represent around 60-70% of dementia cases.

alzheimer’s disease is characterized by changes in the brain, including the abnormal accumulation of toxic amyloid beta plaque, which begins approximately 20 years before patients exhibit symptoms of the disease. mci due to alzheimer’s disease is one of the earliest stages of the disease when symptoms start to be more visible and can be detected and diagnosed. current research efforts are focused on catching and treating patients as early as possible for the best chance of slowing or stopping the progression of alzheimer’s disease.

 

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 as well as related therapeutic adjacencies. 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. today biogen has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics and is focused on advancing research programs in multiple sclerosis and neuroimmunology, alzheimer’s disease and dementia, neuromuscular disorders, movement disorders, ophthalmology, immunology, neurocognitive disorders, acute neurology and pain.

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about eisai co., ltd.

eisai co., ltd. is a leading global pharmaceutical company headquartered in japan. eisai’s corporate philosophy is based on the human health care (hhc) concept, which is to give first thought to patients and their families, and to increase the benefits that health care provides to them. with a global network of r&d facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products to target diseases with high 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 a treatment for alzheimer’s disease, eisai aims to establish the “eisai dementia platform.” through this platform, eisai plans to deliver novel benefits to those living with dementia and their families through constructing a “dementia ecosystem,” by collaborating with partners such as medical organizations, diagnostic development companies, research organizations, and bio-ventures in addition to private insurance agencies, finance industries, fitness clubs, automobile makers, retailers, and care facilities. for more information about eisai co., ltd., please visit .

 

biogen safe harbor 

this news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the private securities litigation reform act of 1995, about potential regulatory discussions, submissions and approvals and the timing thereof; the potential clinical effects of aducanumab; the potential benefits, safety and efficacy of aducanumab; the treatment of alzheimer’s disease; the anticipated benefits and potential of biogen’s collaboration arrangements with eisai; the potential of biogen’s commercial business and pipeline programs, including aducanumab; and risks and uncertainties associated with drug development and commercialization. these statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would” 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 the 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 actual timing and content of submissions to and decisions made by the regulatory authorities regarding aducanumab; regulatory submissions may take longer or be more difficult to complete than expected; 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 aducanumab; unexpected concerns that may arise from additional data, analysis or results obtained during clinical trials; the occurrence of adverse safety events; risks of unexpected costs or delays; the risk of other unexpected hurdles; uncertainty of success in the development and potential commercialization of aducanumab; risks relating to the potential launch of aducanumab, including preparedness of healthcare providers to treat patients, the ability to obtain and maintain adequate reimbursement for aducanumab and other unexpected difficulties or hurdles; failure to protect and enforce biogen’s data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; third party collaboration risks; and the direct and indirect impacts of the ongoing covid-19 pandemic on biogen’s business, results of operations and financial condition. 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 u.s. securities and exchange commission. these statements are based on biogen’s current beliefs and expectations and speak only as of the date of this news 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.

this collaboration aims to develop a disease modifying treatment for synucleinopathies based on network kinetics of α-synuclein misfolding and aggregation

tokyo, japan and cambridge, united kingdom, november 30 2020 – eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) and wren therapeutics ltd. (headquarters: cambridge, uk, “wren”) today announced that the companies have entered into an exclusive research collaboration agreement aiming to advance the discovery of novel small molecules that target α-synuclein for the potential treatment of synucleinopathies including parkinson’s disease and dementia with lewy bodies.

wren possesses a novel network kinetics drug discovery platform that precisely quantifies the effects of small molecules on the protein misfolding and aggregation pathway that causes neurodegenerative diseases. wren’s approach to synucleinopathies is focused on identifying novel small molecules that selectively control the aggregation process of α-synuclein, which is associated with the onset and progression of these diseases. the collaboration will use wren’s network kinetics drug discovery platform, alongside eisai’s extensive experience in drug discovery for neurodegenerative disorders, to accelerate the development of clinical candidates.

dr. samuel cohen, chief executive officer of wren, commented: “we are delighted to have formed this collaboration with eisai, a company with a distinguished track record and company-wide commitment to providing innovative treatments for patients suffering from neurodegenerative diseases. we believe that by combining our unique, predictive and quantitatively driven platform with eisai’s deep expertise in neurology, we can together advance highly differentiated small molecules targeting α-synuclein for the treatment of debilitating protein misfolding disorders such as parkinson’s disease.”

dr. teiji kimura, vice president, chief discovery officer of the eisai neurology business group, commented: “synucleinopathies such as dementia with lewy bodies and parkinson’s disease represent a significant unmet medical need due to the lack of any effective disease-modifying treatments. the accumulation of α-synuclein oligomers with protein misfolding is an important hallmark of these diseases. the wren team, with its world-renowned founding scientists, is pioneering a new and fundamentally different approach to addressing protein misfolding diseases. by integrating capabilities across both companies we expect this exciting collaboration to be uniquely successful in identifying novel disease-modifying therapeutics for patients suffering from dementia with lewy bodies, parkinson’s disease and related disorders.”

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

wren therapeutics ltd.
emer reynolds
email: communications@wrentherapeutics.com

about wren’s novel network kinetics drug discovery platform

wren’s proprietary network kinetics drug discovery platform enables an entirely new approach to drug discovery, designed specifically to address the unique challenges associated with protein misfolding diseases. the kinetics-based approach solves for the distinct molecular reaction network that underlies each misfolding disease and produces a fully predictive, quantitative map of the network and its dynamics. the platform identifies the optimum intervention points in the network to reduce the populations of toxic misfolded and aggregated species, and subsequently makes it possible to identify and optimise molecules with the desired kinetics inhibitory activity.

about synucleinopathies

synucleinopathies are neurodegenerative diseases characterised by the aberrant misfolding and aggregation of α-synuclein in neurons and glial cells. synucleinopathies include parkinson’s disease (pd), dementia with lewy bodies (dlb), and multiple system atrophy (msa).

about eisai co., ltd.

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

for further information on eisai co., ltd., please visit https://www.eisai.com.

about wren therapeutics ltd.

wren is a spin-off company from the university of cambridge (uk) and lund university (sweden), focused on drug discovery and development for protein misfolding diseases. wren is advancing an entirely novel approach to address this class of diseases, based on more than a decade of research from its scientific founders focused on the chemical kinetics of the protein misfolding process. wren’s predictive, quantitative platform is built on concepts from the physical sciences and is a fundamental shift from the descriptive, qualitative methods of traditional biology, which have failed to successfully address these complex systems. wren is using its unique approach to develop a broad pipeline of therapeutics for protein misfolding diseases.

for further information on wren, please visit www.wrentherapeutics.com