news – page 21 – eisai china lnc.-nba直播小9直播

news – page 21 – eisai china lnc.-nba直播小9直播

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.

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) has announced that results from the cardiovascular outcomes trial (camellia-timi 61) in patients treated with lorcaserin hydrochloride (generic name, product name in the u.s.: belviq®, “belviq”) were highlighted in an oral presentation at the european society of cardiology (esc) congress 2018 held in munich, germany, and concurrently published in the new england journal of medicine, one of the world’s most influential medical journals.1 belviq is the first ever weight loss medication approved for chronic weight management which has been proven to not increase the incidence of major cardiovascular (cv) events in a dedicated long-term cardiovascular outcome trial.

this study was conducted at over 400 sites in eight countries including the united states in collaboration with the thrombolysis in myocardial infarction (timi) study group, and is the largest cardiovascular outcome trial conducted to date for a weight loss medication. as the primary safety objective, the study assessed the incidence of major adverse cardiovascular events (mace: defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in 12,000 overweight and obese adults with existing cardiovascular disease or type 2 diabetes mellitus (t2dm) with cardiovascular risk factors who were administered belviq 10 mg twice-daily (median 3.3 years). overall, the median age of patients in the study was 64 and the median body mass index (bmi) was 35kg/m2, with 57% of patients at baseline having t2dm, 90% with hypertension, 94% with hyperlipidemia and 20% with chronic kidney disease. approximately 75% of patients had established atherosclerotic cv disease.

at the time of study completion, mace occurred in 364 of 6,000 patients in the belviq arm (2.0%/year) and 369 of 6,000 patients in the placebo arm (2.1%/year; hazard ratio, 0.99; 95% confidence interval (ci), 0.85-1.14; non-inferiority margin, 1.4). this demonstrated that belviq did not increase the incidence of mace, and therefore the primary safety objective of statistical non-inferiority was met. since the primary safety objective was met, the primary efficacy outcome of incidence of cv death, myocardial infarction, stroke hospitalization for unstable angina, heart failure or any coronary revascularization (mace ) was also assessed. from the results, mace occurred in 707 of 6,000 patients (4.1%/year) in the belviq arm and in 727 of 6,000 patients in the placebo arm (4.2%/year). although statistical superiority was not observed (p=0.55), statistical non-inferiority was confirmed (hazard ratio, 0.97; 95% ci, 0.87-1.07; non-inferiority margin, 1.4).

in exploratory assessments of the efficacy of belviq, at one year, significantly more patients treated with belviq versus placebo lost greater than or equal to five percent of body weight (39% vs. 17%; nominal p-value<0.001) or greater than or equal to ten percent of body weight (15% vs. 5%; nominal p-value<0.001).
the average change in weight from baseline was -4.2 kg with belviq and -1.4 kg with placebo, translating to a 2.8 kg greater net weight loss with belviq (nominal p-value<0.001).

furthermore, treatment with belviq (for a period of one year), on top of standard of care for the respective comorbid conditions in camellia-timi 61, was associated with statistically significant improvements in systolic blood pressure (placebo-subtracted difference -0.9 mm hg), diastolic blood pressure (-0.8 mm hg), heart rate (-1.0 beat per minute), low-density lipoprotein cholesterol (-1.2 mg/dl), triglycerides (-11.7 mg/dl) and non-high-density lipoprotein cholesterol (-2.6 mg/dl).

belviq also reduced hemoglobin a1c (hba1c) in patients with t2dm at baseline (placebo-subtracted difference -0.3%) and reduced the rate of new onset diabetes in patients with pre-diabetes at baseline (3.1%/year with belviq versus 3.8%/year with placebo).

no significant differences were seen in the overall incidence of serious adverse events between belviq and placebo (31% vs. 32%), and the overall safety profile for belviq in camellia-timi 61 was consistent with that of the approved label. dizziness, fatigue, headache, nausea and diarrhea were the most commonly reported adverse events in camellia-timi 61. adverse events possibly leading to study discontinuation were more frequent with belviq versus placebo (7.2% vs. 3.7%), with the most commonly reported adverse events in this category for belviq being dizziness, fatigue, headache, diarrhea and nausea.

further results of analyses of the study will be presented on october 4 at the european association for study of diabetes (easd) annual meeting held in berlin, germany.

by continuing to provide additional clinical and scientific information regarding belviq, eisai continues to make further contributions to address unmet medical needs and increase the benefits for patients and their families.

 

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

 

[notes to editors]
1. about lorcaserin hydrochloride (u.s. brand name: belviq, once daily formulation u.s. brand name: belviq xr)
discovered and developed by arena pharmaceuticals, inc. (headquarters: california, united states, president and ceo: amit d. munshi), lorcaserin is a novel chemical entity that is believed to decrease food consumption and promote satiety by selectively activating serotonin 2c receptors in the brain. activation of these receptors may help a person eat less and feel full after eating smaller amounts of food. lorcaserin was approved in june 2012 by the fda as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (bmi) of 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition, and was launched in the united states under the brand name belviq in june 2013 after receiving a final scheduling designation from the u.s. drug enforcement administration (dea). in addition, lorcaserin has been made available in south korea via a third-party distributor from 2015. lorcaserin was approved in mexico in july 2016 and in brazil in december 2016, with the same indication as for the united states.
furthermore, belviq xr, a once-daily formulation of lorcaserin aiming to increase convenience of administration for patients, was approved in the united states in july 2016.
in january 2017, eisai acquired all of arena’s rights to develop and market belviq.
the most common adverse reactions observed in multiple phase iii clinical studies on lorcaserin were headache, dizziness, fatigue, nausea, dry mouth and constipation in patients without diabetes, and hypoglycemia, headache, back pain, cough and fatigue in patients with diabetes. for further information on lorcaserin in the united states, including important safety information (isi), please visit the belviq product website ().

2. about the cardiovascular outcomes trial, camellia-timi61 study
the camellia (cardiovascular and metabolic effects of lorcaserin in overweight and obese patients) timi 61 study was the largest double-blind, placebo-controlled, parallel-group phase iiib/iv study among weight loss medications. the primary safety objective was to evaluate the incidence of major adverse cardiovascular events (mace), defined as cardiovascular death, myocardial infarction or stroke. if the primary safety objective was met, the efficacy objective was to evaluate the impact of lorcaserin on the incidence of mace , defined as mace or hospitalization due to unstable angina or heart failure, or any coronary revascularization. secondary objectives included evaluation for the potential to delay or prevent conversion to t2dm in patients with pre-diabetes or no diabetes at baseline and improvement of glycemic control in patients with t2dm.

3. about the timi study group
the timi study group is an academic research organization based at brigham and women’s hospital that has been leading practice-changing cardiovascular clinical trials for 30 years.

4. about the new england journal of medicine
the new england journal of medicine (nejm) is the world’s leading medical journal and website, published continuously for over 200 years. nejm has the highest journal impact factor of all general medical journals (2017 journal citation reports®, clarivate analytics, 2018).

 

1 bohula, e. a., cardiovascular safety of lorcaserin in overweight and obese patients, the new england journal of medicine, 2018.

tokyo august 23, 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 european commission (ec) has granted a marketing authorization for the oral receptor tyrosine kinase (rtk) inhibitor lenvima® (lenvatinib mesylate) as a single agent for the first-line treatment of adult patients with advanced or unresectable hepatocellular carcinoma (hcc) who have received no prior systemic therapy. this is the first new first-line treatment option for advanced or unresectable hcc to be approved in europe in approximately 10 years.

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

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 41% versus sorafenib 12% (p<0.0001).

in the eu package insert, the most frequently reported adverse reactions (occurring in ≥30% of patients) are hypertension (44.0%), diarrhoea (38.1%), decreased appetite (34.9%), fatigue (30.6%), and weight decreased (30.4%).

liver cancer is the second leading cause of cancer-related death and is estimated to be responsible for 750,000 deaths per year globally, with 780,000 cases newly diagnosed each year.1 hcc accounts for 85% to 90% of liver cancer cases. treatment options for unresectable hcc are limited and the prognosis is poor, making this an area of high unmet medical need.

currently, lenvima is also available under the product name kisplyx® in combination with everolimus for use in the treatment of renal cell carcinoma (second-line treatment) in europe. lenvima is available for use in the treatment of thyroid cancer in over 50 countries including in europe, japan and the united states.  in japan, approximately 3,000 hcc patients have been treated with lenvima since the approval of the hcc indication in march 2018.

 

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

 

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 to europe, lenvima has been approved as a treatment for hepatocellular carcinoma in japan (march 2018) and the united states (august 2018) as well. eisai has submitted applications for an indication covering hepatocellular carcinoma in mainland china (october 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 actual 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 (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/keytruda combination to support 11 potential indications in six types of cancer, as well as a basket trial targeting six additional cancer types.

 

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. 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 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; p<0.0001) per recist 1.1. lenvima showed nearly 3.5 times the orr of sorafenib: 41% (95% ci: 36-45) (complete response (cr)=2.1% (n=10), partial response (pr)=38.5% (n=184)) vs. 12% (95% ci: 9-15) (cr=0.8% (n=4), pr=11.6% (n=55)) per blinded independent imaging review based on mrecist criteria, respectively (p<0.0001), and 19% (95% ci: 15-22) with lenvima versus 7% (95% ci: 4-9) 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 2018391 (10126), 1163-1173 (published online on february 9, 2018).

 

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.1 there is a large regional difference, with about 80% of new cases occurring in asian regions, including china and japan. hepatocellular carcinoma accounts for 85% to 90% of primary liver cancer cases. hepatocellular carcinoma 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 hepatocellular carcinoma is on the rise. early stage hepatocellular carcinoma is treatable by a wide variety of means, including surgery, radiofrequency ablation, ethanol injection, and chemoembolization therapy, but treatment options for unresectable hepatocellular carcinoma are limited and the prognosis is very poor, meaning that this is an area of high unmet medical need.

 1  globocan2012: estimated cancer incidence, mortality and prevalence worldwide in 2012. 

on august 22, the “2018 great suzhou best employer award ceremony” was held at suzhou jinji lake international convention center. eisai china inc. (eci) has been accredited great suzhou best employer for second consecutive years. the “best employer” selection project has been organized for 5 years since 2013. it is now the most influential and appealing event in suzhou for employer brand selection. this project has successfully attracted the participation of over one thousand enterprises and the attention of millions of employees and has become an annual ceremony for the display of employer brands in suzhou. 


“great suzhou best employer” was awarded to eci for second consecutive years

eisai china inc. is a pharmaceutical company wholly-owned by eisai co., ltd. of japan. eisai china inc. has been rooted in suzhou industrial park for 22 years since 1996, importing and producing more than ten varieties of original drugs, mainly concentrating on neurology, oncology and gastrointestinal area. eisai has always been committed to the corporate philosophy of human health care (hhc), providing chinese doctors with supports on medical diagnosis and treatment and offering patients and their families high quality, environmental-friendly, safe and satisfactory products and services. to meet the growing demand for high quality drugs and high-speed business development in china, eisai invested us$230 million in the construction and production of a new factory in baiyu road, suzhou industrial park in 1996. the new factory covers a land area of 23,000 square meters. after two expansions, eisai invested another us$120 million in 2010 to purchase a land in xingpu road, suzhou industrial park for the construction of a new factory integrating r&d, production and logistics. the new factory covers an area of 130,000 square meters. in november 2014, the construction of a new parenteral facility was completed; in november 2017, the construction of an oral solid dose production facility was completed. in december 2017, eisai obtained the drug manufacturing certificate. in the future, the new factory will provide high quality and satisfactory products overseas as well as meeting the demand of chinese patients for clinical medication.

hhc” is the corporate philosophy that eisai has always been adhering to. every staff of eisai spares 1% of the business time to “hhc” activities. we get into communities and approach to patients, listening to the voice of patients and their families to know their sufferings so as to better satisfy the demands of patients. eisai actively gives back to the society and takes on social responsibility. eisai’s hhc activities, including “eisai” with love – approaching the elderly, worry-free for health with “eisai” – care for patients with gastropathy, blood donation for children with leukemia, and etc., have been recognized and praised by the society. eisai has been given, for several times, the “best charity project award” and the “most responsible enterprise for the society” of the industrial park. meanwhile, eisai has set up eisai china scholarship with seven famous universities, with an accumulation of approximately rmb7.29 million yuan to students to inspire them to get into the medical and pharmaceutical industry. 

we have always been taking the improvement of employee capability as one of its long-term strategies. in order to enhance the sense of belonging of employees and strengthen corporate cohesion, we have set up the “honorary staff award” for the employees who have been serving the company for 5, 10, 15 and 20 years respectively. by the end of march 2018, we have 23 employees work for the company for more than 20 years, 71 for above 15 years, 182 for above 10 years and 542 for above 5 years. employees’ ability enhancement and loyalty are the greatest return and recognition for the company. at eisai, employees have sound career development space and grow in sync with the company. we fully respect every employee, encourage knowledge innovation and strict ethical guidelines, and promote a cooperative working atmosphere. under the harmonious labor relations, we have been given many awards, such as the “aaaa labor security unit” in 2017. with its competitive compensation mechanism and sound welfare system, eisai provides comprehensive care for its employees. 

tokyo august 17, 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 u.s. food and drug administration (fda) approved the kinase inhibitor lenvima® (lenvatinib mesylate) for the first-line treatment of patients with unresectable hepatocellular carcinoma (hcc). this approval was based on results from reflect (study 304), where lenvima demonstrated a proven treatment effect on overall survival (os) *1 by statistical confirmation of non-inferiority, as well as statistically significant superiority and clinically meaningful improvements in progression-free survival (pfs) *2 and objective response rate (orr) *3 when compared with sorafenib in patients with previously untreated unresectable hcc. this is the second approval of lenvima for use in the treatment of hcc following approval in japan earlier this year, and the first new systemic therapy to be approved in the u.s. for the first-line treatment of unresectable hcc in approximately 10 years.

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<0.001) and orr: lenvima 41% versus sorafenib 12% (p<0.001).

in the u.s. package insert, the most common adverse reactions (≥20%) observed in patients treated with lenvima were hypertension, fatigue, diarrhea, decreased appetite, arthralgia/myalgia, decreased weight, abdominal pain, palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hemorrhagic events, hypothyroidism and nausea. the most common serious adverse reactions (≥2%) reported in patients treated with lenvima were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%) and decreased appetite (2%).

the most common adverse reactions (≥20%) observed in patients who received sorafenib were palmar-plantar erythrodysesthesia syndrome, diarrhea, fatigue, hypertension, abdominal pain, decreased appetite, rash, decreased weight and arthralgia/myalgia. the most common serious adverse reactions (≥2%) reported in patients who received sorafenib were ascites (2%) and abdominal pain (2%).

“unresectable hepatocellular carcinoma is an extremely difficult-to-treat cancer, with no new first-line systemic therapy options for more than a decade,” said dr. ghassan abou-alfa, medical oncologist, memorial sloan kettering cancer center. “reflect is the first-ever positive phase iii trial against an active comparator in unresectable hcc. the efficacy and safety data from reflect are important findings for oncologists and others in the multidisciplinary teams who treat liver cancer, as well as for our patients who are affected by it.”

liver cancer is the second leading cause of cancer-related death and is estimated to be responsible for 750,000 deaths per year globally, with 780,000 cases newly diagnosed each year.1 hcc accounts for 85% to 90% of liver cancer cases. treatment options for unresectable hcc are limited, and the prognosis is very poor, making this an area of high unmet medical need.

lenvima, a kinase inhibitor, was first approved in the u.s. in february 2015 for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (dtc). in may 2016, lenvima was approved in the u.s. in combination with everolimus, for patients with advanced renal cell carcinoma (rcc) following one prior anti-angiogenic therapy. under the collaboration, eisai and merck & co., inc., kenilworth n.j., u.s.a. initiated co-commercialization activities for lenvima in the u.s. in june 2018. since the initial launch, more than 10,000 patients were 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.

 

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

 

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 to the united states, lenvima has been approved as a treatment for hepatocellular carcinoma in japan as well. eisai has submitted applications for an indication covering hepatocellular carcinoma in europe (july 2017), mainland china (october 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 actual 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 (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/keytruda combination to support 11 potential indications in six types of cancer, as well as a basket trial targeting six additional cancer types.

 

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. 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 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<0.001) 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: 41% (95% ci: 36-45%) (complete response (cr)=2.1% (n=10), partial response (pr)=38.5% (n=184)) vs. 12% (95% ci: 10-16%) (cr=0.8% (n=4), pr=11.6% (n=55)) per blinded independent imaging review based on mrecist criteria, respectively (p<0.001), and 19% (95% ci: 15-22) with lenvima versus 7% (95% ci: 4-9) 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 2018391 (10126), 1163-1173 (published online on february 9, 2018).

 

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.1 there is a large regional difference, with about 80% of new cases occurring in asian regions, including china and japan. hepatocellular carcinoma accounts for 85% to 90% of primary liver cancer cases. hepatocellular carcinoma 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 hepatocellular carcinoma is on the rise. early stage hepatocellular carcinoma is treatable by a wide variety of means, including surgery, radiofrequency ablation, ethanol injection, and chemoembolization therapy, but treatment options for unresectable hepatocellular carcinoma are limited and the prognosis is very poor, meaning that this is an area of high unmet medical need.

 globocan2012: estimated cancer incidence, mortality and prevalence worldwide in 2012. 

aug. 4, 2018, china top 100 pharmaceutical enterprises list was released in the 35thchina pharmaceutical industry information annual conference 2018. following the 97th place in 2015, and the 92nd place in 2016, eisai (china) ranked 84th in the top 100 list 2017.


eisai china holdings ltd. ranked 84th in china top 100 pharmaceutical enterprises list

with more than 20 years’ development, eisai has established a development mode consisting of eisai china holdings ltd. for capital control and management, while eisai china inc., eisai (liaoning) pharmaceutical co., ltd. and eisai (suzhou) trading co., ltd. for business support. currently, the total registered capital of eisai in china is usd108.54 million. eisai china specializes in neurology, oncology and gastrointestinal areas, and expands to the generic business. the sales volume reached rmb3 billion yuan in 2017.

“eisai china always keeps to the faith in providing drugs with high quality and reasonable price and addressing the diverse needs of patients and their families. as an important strategy of eway 2025, eisai china will actively expand the market coverage including the low-tier market,” said ms. yanhui feng, corporate officer of eisai co. ltd. and president of eisai china holdings ltd. “eisai china sticks, all the time, to the corporate philosophy that the interests of patients and their families are our priority and we will contribute to improving their well-beings, constantly bringing in high quality drugs, proactively expanding and innovating business mode, serving chinese patients and their families.”

china pharmaceutical industry information annual conference is held by china national pharmaceutical industry information center. based on the annual statistic report of china pharmaceutical industry published by ministry of industry and information technology, china top 100 pharmaceutical enterprises list reflects the status of china pharmaceutical industry, with the final data obtained through the first, second, third and fourth reviews in the materials of pharmaceutical enterprises. according to the data analysis, with the constant expansion of the industrial scale of china’s pharmaceutical industry, the threshold of the top 100 enterprises in china’s pharmaceutical industry has increased year by year, and the lowest threshold of the top 100 enterprises has increased from rmb2.4 billion yuan of main business income in 2016 to rmb2.56 billion yuan in 2017. the overall size of the top 100 companies has continued to grow rapidly.

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that it has entered into an agreement to grant exclusive development and marketing rights for its anti-obesity agent lorcaserin hydrochloride (generic name, product name in the united states: belviq®, product name for once-daily formulation in the united states: belviq xr®, “lorcaserin”) in china (including hksa and chinese macao) to cy biotech (headquarters: taipei, chinese taiwan, “cyb”).

under this agreement, eisai will supply cyb with lorcaserin. eisai will receive a one-time contractual payment and milestone payments dependent upon acquisition of regulatory approval. in addition, eisai has the option rights to co-promote lorcaserin with cyb in china (excluding hksa and chinese macao), as well as the option rights to market lorcaserin in hksa and chinese macao.

lorcaserin is a novel chemical entity that is believed to decrease food consumption and promote satiety by selectively activating serotonin 2c receptors in the brain. lorcaserin was approved in june 2012 by the u.s. food and drug administration (fda) as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (bmi) of 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related co-morbid condition, and was launched in the united states in june 2013. lorcaserin was approved in mexico in july 2016 and in brazil in december 2016, with the same indication as for the united states. in chinese taiwan, lorcaserin was developed by cyb, who obtained approval in july 2017 and launched lorcaserin in chinese taiwan in october 2017.

by entering into this agreement with cyb, which already has a track record in developing and marketing lorcaserin in chinese taiwan, eisai is aiming to accelerate the delivery of lorcaserin to patients in these regions.

 

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

 

[notes to editors]

1. about lorcaserin hydrochloride (product name in the united states: belviq, product name for once-daily formulation in the united states: belviq xr, “lorcaserin”)
discovered and developed by arena pharmaceuticals, inc., lorcaserin is a novel chemical entity that is believed to decrease food consumption and promote satiety by selectively activating serotonin 2c receptors in the brain. activation of these receptors may help a person eat less and feel full after eating smaller amounts of food. lorcaserin was approved in june 2012 by the u.s. food and drug administration (fda) as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (bmi) of 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related co-morbid condition, and was launched in the united states under the brand name belviq in june 2013 after receiving a final scheduling designation from the u.s. drug enforcement administration (dea). in addition, lorcaserin has been made available in south korea via a third-party distributor from 2015. lorcaserin was approved in mexico in july 2016 and in brazil in december 2016, with the same indication as for the united states. furthermore, belviq xr, a once-daily formulation of lorcaserin aiming to increase convenience of administration for patients, was approved in the united states in july 2016. in january 2017, eisai acquired all of arena’s rights to develop and market lorcaserin.

the most common adverse reactions observed in multiple phase iii clinical studies on lorcaserin were headache, dizziness, fatigue, nausea, dry mouth and constipation in patients without diabetes, and hypoglycemia, headache, back pain, cough and fatigue in patients with diabetes.

a cardiovascular outcomes trial conducted in multiple countries, including the united states, with 12,000 patients found that long-term treatment with lorcaserin does not increase incidence of mace (major adverse cardiovascular events including myocardial infarction, stroke and cardiovascular death), and the primary safety objective of the trial was met. in addition, regarding the incidence of mace (consisting of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization due to unstable angina, heart failure or coronary revascularization) which was the primary efficacy endpoint, although statistical superiority to placebo was not met, the results successfully confirmed statistical non-inferiority for lorcaserin. in this trial, lorcaserin also demonstrated an improvement in multiple cardiovascular risk factors including blood pressure, lipids, blood glucose and renal function as well as a reduction in conversion to type 2 diabetes mellitus (t2dm) in patients without diabetes. furthermore, in additional subgroup analyses, on a background of lifestyle modification, it was observed that lorcaserin improved long-term weight loss compared to placebo, including in subpopulations with t2dm and obstructive sleep apnea.

 

2. about cy biotech company ltd.

cy biotech company ltd. (cyb) is a pharmaceutical company established in april 2011 with its headquarters in chinese taiwan. in 2012, cyb launched a wholly-owned subsidiary chuang yi trading limited in shanghai. cyb obtained the exclusive rights for marketing and distributing lorcaserin in chinese taiwan and has been marketing lorcaserin in chinese taiwan since 2017. aiming to be an innovative leader in self-paid pharmaceutical and health products with a wide range of indications, cyb is striving to improve the quality of life (qol) of patients in greater china.

tokyo & kenilworth, n.j., july 31, 2018 – eisai co., ltd. and merck & co., inc. kenilworth, n.j., u.s.a. (nyse:mrk), known as msd outside the united states and canada, announced today that the u.s. food and drug administration (fda) granted breakthrough therapy designation for lenvima® (generic name: lenvatinib mesylate), the orally available kinase inhibitor discovered by eisai, in combination with merck & co., inc., kenilworth, n.j., u.s.a.’s anti-pd-1 therapy keytruda® (generic name: pembrolizumab) for the potential treatment of patients with advanced and/or metastatic non-microsatellite instability high (msi-h)/proficient mismatch repair (pmmr) endometrial carcinoma (ec) who have progressed following at least one prior systemic therapy.

the lenvima/keytruda combination therapy is being jointly developed by eisai and merck & co., inc., kenilworth, n.j., u.s.a. as part of the strategic collaboration announced in march 2018. this is the third breakthrough therapy designation for lenvima and the second breakthrough therapy designation for lenvima in combination with keytruda following the breakthrough therapy designation for the combination for advanced and/or metastatic renal cell carcinoma announced in january 2018.

the breakthrough therapy designation is an fda program intended to expedite development and review of medicines for serious or life-threatening conditions. in order to qualify for this designation, preliminary clinical evidence must demonstrate that the drug may provide substantial improvement over currently available therapy on at least one clinically significant endpoint. the benefits of this breakthrough therapy designation include more intensive guidance on an efficient clinical development program, access to senior fda managers and experienced fda staff to help accelerate review time, as well as eligibility for rolling review and potentially priority review.

this breakthrough therapy designation was based on interim results of the ec cohort in study 111/keynote-146, which were presented in june 2018 at the 54th american society of clinical oncology (asco) annual meeting.1,2 study 111/keynote-146 is a multi-center, open-label, single-arm phase 1b/2 basket trial evaluating the efficacy and safety of lenvima in combination with keytruda in patients with selected solid tumors.

“this second breakthrough therapy designation for the lenvima/keytruda combination represents another step forward in our collaboration with eisai and supports the continued evaluation of this combination in more than 11 types of cancer,” said dr. roy baynes, senior vice president and head of global clinical development, chief medical officer, merck research laboratories. “we will continue to work closely with eisai to build on the robust data for the lenvima/keytruda combination in advanced endometrial carcinoma in an effort to offer a new option for these patients and potentially help address a critical unmet need.”

“we designed study 111 to learn as much as we could about the lenvima/keytruda combination as efficiently as possible, driven by a sense of urgency to bring forward a potential new treatment option for patients in need,” said dr. takashi owa, vice president and chief medicine creation officer, oncology business group, eisai. “we are encouraged by the continued activity seen in patients with endometrial carcinoma, and the latest breakthrough therapy designation for lenvima and keytruda has strengthened our commitment, as part of our human health caremission, to expedite the path to ultimately benefitting patients living with endometrial carcinoma as quickly as possible.”

 

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

 

about study 111/keynote-146
study 111/keynote-146 is a multicenter, open-label, single-arm phase 1b/2 basket trial evaluating the combination of lenvima (20 mg/day) with keytruda (200 mg intravenously every three weeks) in patients with selected solid tumors (renal cell carcinoma, ec, non-small cell lung cancer, urothelial cancer, squamous cell head and neck cancer, and melanoma). patients were not preselected based on msi or pd-l1 tumor biomarker status. the primary endpoint of the phase 1b study was to determine the maximum tolerated dose of lenvima and keytruda in combination. the primary endpoint of the phase 2 portion is investigator-assessed objective response rate (orr) at week 24 based on immune-related recist (irrecist). the secondary efficacy endpoints included orr, progression-free survival and duration of response for patients with complete or partial responses. fifty-three patients with previously treated, metastatic ec were evaluated in the ec cohort. currently, the phase 2 part is ongoing as an ec cohort expansion. this study is being conducted under an existing strategic collaboration between the two companies.

a randomized, international, two-arm phase 3 study in recurrent ec is underway (study 309/keynote-775; nct03517449; please visit  for more information).

about endometrial carcinoma

endometrial cancer begins in the inner lining of the uterus (endometrium), and nearly all cancers of the uterus are endometrial carcinomas.3 in 2018, it is estimated there will be approximately 63,230 new cases of uterine cancer, and there will be approximately 11,350 deaths from uterine cancer (with the figures for endometrial cancer being slightly lower than this combined estimate).4 stages of endometrial cancer range from stage 1 through 4.5 the five-year survival rate for women diagnosed with stage 1a endometrial cancer is 88% and drops to 15% for those diagnosed with stage 4b.

 

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 develop and commercialize lenvima jointly, both as monotherapy and in combination with merck & co., inc. kenilworth n.j., u.s.a.’s anti-pd-1 therapy keytruda. in addition to ongoing clinical studies of the combination, the companies will jointly initiate new clinical studies evaluating the combination to support 11 potential indications in six types of cancer (bladder cancer, endometrial cancer, head and neck cancer, hepatocellular carcinoma, melanoma and non-small cell lung cancer), as well as a basket trial targeting six additional cancer types. the combination of lenvima and keytruda is investigational. the efficacy and safety of this combination has not been established. the lenvima/keytruda combination is not approved in any cancer types today.

 

about lenvima® (lenvatinib mesylate
lenvima, discovered and developed in-house by eisai, is an orally administered receptor tyrosine kinase (rtk) inhibitor with a novel binding mode that selectively inhibits the kinase 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 proangiogenic and oncogenic pathway-related rtks (including the platelet-derived growth factor (pdgf) receptor pdgfrα; kit; and ret) involved in tumor proliferation.

currently, eisai has obtained approval for lenvima as a treatment for refractory thyroid cancer in over 50 countries, including the united states, japan, and in europe. additionally, eisai has obtained approval for the agent in combination with everolimus as a treatment for renal cell carcinoma (second-line) in over 40 countries, including the united states and in europe. in europe, the agent was launched under the brand name kisplyx® for renal cell carcinoma.

furthermore, lenvima is approved in japan for use in the treatment of unresectable hepatocellular carcinoma. eisai has submitted applications for an indication covering hepatocellular carcinoma in the united states and europe (july 2017), mainland china (october 2017) as well as chinese taiwan (december 2017).

 

about keytruda® (pembrolizumab) 
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.

 

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 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 .

 

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 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 .

 

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 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 ().

 

  1. makker v, et al. lenvatinib pembrolizumab in patients with advanced endometrial cancer: update results. asco meetingabstract, 2018; #5596
    2. makker v, et al. biomarker results and preclinical rationale for combination lenvatinib and pembrolizumab in advancedendometrial carcinoma. asco meeting abstract, 2018; #5597
    3. american cancer society. what is endometrial cancer. .
    4. american cancer society. key statistics for endometrial cancer. .
    5. american cancer society. endometrial cancer stages..
    6. american cancer society. endometrial cancer survival rates, by stage. .

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) and biogen inc. (nasdaq: biib) (headquarters: cambridge, massachusetts, united states, ceo: michel vounatsos, “biogen”) announced detailed results from the phase ii study (study 201) with ban2401, an anti-amyloid beta (aβ) protofibril antibody, in 856 patients with early alzheimer‘s disease as part of session dt-01 “recent developments in therapeutics (presentation number: dt-01-07) at the alzheimer’s association international conference (aaic) 2018 being held in chicago, illinois, united states on july 25. this abstract was accepted for late breaking oral presentation at aaic.

study 201 (clinicaltrials.gov identifier nct01767311) 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. patients were randomized to five dose regimens, 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly and 10 mg/kg biweekly, 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 study assessed changes from baseline to 18 months in biomarkers measuring the underlying disease pathophysiology, including changes in amyloid accumulated in the brain as measured by amyloid pet (positron emission tomography). the clinical endpoints of alzheimer’s disease composite score (adcoms), alzheimer‘s disease assessment scale-cognitive subscale (adas-cog) and clinical dementia rating sum of boxes (cdr-sb)  were also assessed from baseline to 18 months of treatment.

through bayesian interim analyses, the highest doses of 10 mg/kg monthly and 10 mg/kg biweekly were determined to be the treatment dosages with higher efficacy early in the trial, and as a result, the proportion of patients allocated to these treatment arms was greater (placebo: 247 patients, 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, 10 mg/kg biweekly: 161 patients). following a regulatory request (outside of the united states) in july 2014, the allocation of apoe4 carriers to the 10 mg/kg biweekly treatment arm was restricted, resulting in fewer apoe4 carriers  in this arm and more patients being allocated to the 10 mg/kg monthly treatment arm.

ban2401 demonstrated a dose-dependent reduction in amyloid plaques as measured by amyloid pet, and this reduction was statistically significant at all doses. at the highest dose of ban2401 (10 mg/kg biweekly), an analysis of amyloid accumulated in the brain using standardized pet as measured on the centiloid scale showed an observed mean at baseline of 74.5 and at 18 months of 5.5. using a mixed-effects model with repeated measures (mmrm), the mean reduction in amyloid load was 70 units, which was statistically significant (p<0.0001). in amyloid pet image visual read, ban2401 demonstrated a dose dependent conversion from amyloid positive to negative, and at the highest dose, 81% of patients converted from amyloid positive to negative at 18 months (p<0.0001).

conventional statistical methods on predefined clinical endpoints at the 18 month final efficacy time point confirmed a dose-dependent slowing in cognitive decline from baseline on adcoms. the highest treatment dose of 10 mg/kg biweekly demonstrated a statistically significant slowing of clinical decline of 30% compared to placebo at 18 months (p=0.034). a statistically significant slowing of decline on adcoms was observed as early as 6 months (p<0.05) as well as at 12 months (p<0.05). dose-dependent slowing in cognitive decline from baseline on adas-cog was also observed for ban2401, with the highest treatment dose of ban2401 demonstrating a significant slowing of clinical decline compared to placebo at 18 months (47% slower decline, p=0.017). furthermore, dose-dependent slowing in cognitive decline from baseline on cdr-sb was observed, surpassing the pre-specified difference of 25% over the duration of the study. at 18 months, slowing of clinical decline for the highest treatment dose of ban2401 compared to placebo on cdr-sb was 26%. the rate of clinical decline for the placebo group was consistent with the results of research by the alzheimer’s disease neuroimaging initiative (adni) in the united states.

in a bayesian analysis of adcoms at 12 months, the estimated probability that the highest dose of ban2401 slows clinical decline more than placebo was 98%. while the criteria for early success at 12 months was pre-specified as an 80% or higher estimated probability of demonstrating a clinically significant difference (a 25% or greater slowing in clinical decline) from baseline compared to placebo, the actual probability for this criteria was 64% according to bayesian analysis.

a dose-dependent increase in aβ levels in cerebrospinal fluid (csf) in patients on ban2401 (highest dose at 18 months: p<0.0001) was observed. combined analysis of patients receiving ban2401 at 10 mg/kg (either monthly or biweekly) demonstrated a statistically significant reduction in total tau over time compared to placebo (p<0.05).

ban2401 demonstrated an acceptable tolerability profile through 18 months of study drug administration.  the incidence rate of treatment-related adverse events was 26.5% for the placebo arm, 53.4% for the 10 mg/kg monthly treatment arm and 47.2% for the 10 mg/kg biweekly treatment arm. the most common treatment emergent adverse events were amyloid related imaging abnormalities (aria) and infusion-related reactions. incidence of aria-e (edema) was 9.9% at the highest treatment dose, and not more than 10% in any of the treatment arms. incidence of aria-e in apoe4 carriers was 14.6% at the highest dose. per protocol, all patients presenting with aria-e on mri were discontinued in the study. the incidence rate of serious adverse events was 17.6% for the placebo arm, 12.3% for the 10 mg/kg monthly treatment arm and 15.5% for the 10 mg/kg biweekly arm.

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 ii study of ban2401; the potential clinical effects of ban2401; the potential benefits, safety, and efficacy of ban2401 and therapies for other neurological diseases; the clinical development program for ban2401; risks and uncertainties associated with drug development and commercialization; the timing and status of current and future regulatory filings; biogen‘s strategy and plans; 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,” “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 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 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

eisai co., ltd. biogen inc.
 

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

eisai inc.
patricia_councill@eisai.com
1-201-746-2139

 

public affairs
1-781-464-3260
public.affairs@biogen.com

  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.

  1. 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 an exploratory endpoint as well as dose responsiveness through 16 interim analyses that assessed potential for early success, an analysis based on adcoms at 12 months, and a comprehensive final analysis at 18 months. 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 and 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).

  1. 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 alzheimer‘s disease symptoms and changes in memory. this study 201 utilizes adcoms as its key endpoint for assessing clinical symptoms.

  1. 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 and marks it with positron. amyloid pet imaging enables the assessment of pathology change and assistance of diagnosis of patients with alzheimer’s-disease including mci, and estimates the clinical effect of disease modifiers based on the amyloid hypothesis. suvr (standard uptake value ratio) calculates the ratio of strength of accumulation of pet tracer in a region of interest in the brain to an area of the brain (reference region) which shows low and stable accumulation of pet tracer. these suvr values can be used to quantitatively compare and evaluate the accumulation of amyloid. when integrating and assessing biomarkers of the change in aβ accumulation measured by different tracers, it is necessary to compensate for the differences in measured values between the pet tracers. this has led to the development of a 100-point scale by the gaain centiloid project, termed “centiloid,” which is an average value of zero in “high certainty” amyloid negative subjects and an average of 100 in “typical” alzheimer‘s disease (ad) patients (klunk et al., 2015). in this study, this centiloid scale was used to standardize suvr measurement values to evaluate the decrease in amyloid burden.

  1. 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.

  1. 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 .

  1. 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 weissman, 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, neuroimmunology, movement disorders, neuromuscular disorders, pain, ophthalmology, neuropsychiatry, and acute neurology. biogen also manufactures and commercializes biosimilars of advanced biologics.

to learn more, please visit .

  1. about bioarctic abbioarctic 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).
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