news – page 6 – eisai china lnc.-pg电子app

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that it has received notification that aricept^® (donepezil hydrochloride), a treatment for alzheimer’s disease and dementia with lewy bodies that was discovered and developed in-house, has been granted category 2* status based on the results of a reexamination of its efficacy, dosage and administration for the treatment of dementia with lewy bodies (dlb) in japan. in conjunction with this, eisai plans to promptly submit an application for a partial change to label regarding dosage and administration. the indication for dlb remains unchanged.

 

the indication of “suppression of progression of dementia symptoms in dlb” was approved in september 2014, primarily based on a phase ii study (study 431) and phase iii study (study 341) conducted by eisai on people living with dlb in japan. in accordance with the condition for the approval of this indication, “a clinical trial to verify the efficacy and safety of the drug in patients with dlb should be conducted and the results of the trials and analyses should be submitted promptly after completion,” eisai conducted a post-marketing clinical study (study 419) to evaluate the efficacy and safety of the drug in patients with dlb.

 

the results of study 419 did not show a statistically significant difference between the placebo group and the aricept group in the primary endpoint of global function (cibic-plus** comprehensive assessment), but the re-examination based on post-marketing studies, including the results of study 419, stated that “at present, the evaluation of clinical function in dlb using cibic-plus is not always sufficiently established as an evaluation method, and it is difficult to comprehensively evaluate the efficacy of this drug for dlb, although efficacy was seen in some patients. on the other hand, treatment with this drug showed a trend toward improvement in cognitive function (mmse***), and this result is consistent with the results of the clinical trial at the time of approval of the drug. since there are a certain number of patients who can be expected to benefit from the administration of this drug, it was concluded that the efficacy should be evaluated after the start of administration, and administration should only continue if efficacy is confirmed.”

therefore, it was concluded that the approved label (dose and administration) and package insert should be appropriately revised (category 2).

the condition of the approval was lifted as of the date of receipt of the reexamination results.

 

along with this prompt application for a partial change to label regarding dosage and administration for the dlb indication, eisai will place the highest priority on the provision of proper use and safety information for this drug, and will make continued contributions to address the diversified needs of, and increase the benefits provided to people living with dlb and their families.

 

media inquiries:

public relations department,

eisai co., ltd.

81-(0)3-3817-5120

 

* category 2: partial changes in approval (modifications in approved items as directed)

** cibic-plus (the clinician’s interview-based impression of change plus caregiver input): a validated clinical instrument used to measure change in global function through an interview with patients and their caregivers. patients are evaluated by an assessor who is independent from the attending physician on a 7-point scale (very much improved, much improved, minimally improved, no change, minimally worse, much worse and very much worse) in four major categories: general, mental/cognitive state, behavior, and activities of daily living.

*** mmse (mini-mental state examination): a method for assessing cognitive function. comprised of the categories orientation, memorization, attention, calculation, recent and distant memory, comprehension, reading and writing, as well as design. test scores range from 30 (normal) to 0 (severely impaired).

· all key secondary endpoints also met, demonstrating highly statistically significant results

· profile of amyloid-related imaging abnormalities (aria) incidence was within expectations

· eisai aims to file for traditional approval in the u.s., and to submit marketing authorization applications in japan and europe by the end of eisai fy2022, which ends on march 31, 2023

 

tokyo and cambridge, eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) and biogen inc. (nasdaq: biib, corporate headquarters: cambridge, massachusetts, ceo: michel vounatsos, “biogen”) announced positive topline results from eisai’s large global phase 3 confirmatory clarity ad clinical trial of lecanemab (development code: ban2401), an investigational anti-amyloid beta (aβ) protofibril antibody for the treatment of mild cognitive impairment (mci) due to alzheimer’s disease (ad) and mild ad (collectively known as early ad) with confirmed presence of amyloid pathology in the brain. lecanemab met the primary endpoint (cdr-sb: clinical dementia rating-sum of boxes*) and all key secondary endpoints with highly statistically significant results. eisai will discuss this data with regulatory authorities in the u.s., japan and europe with the aim to file for traditional approval in the us and for marketing authorization applications in japan and europe by the end of eisai’s fy2022, which ends march 31, 2023. additionally, eisai will present the clarity ad study results on november 29, 2022, at the clinical trials on alzheimer’s congress (ctad), and publish the findings in a peer-reviewed medical journal.

 

* cdr-sb is a numeric scale used to quantify the various severity of symptoms of dementia. based on interviews of people living with ad and family/caregivers, qualified healthcare professionals assess cognitive and functional performance in six areas: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. the total score of the six areas is the score of cdr-sb, and cdr-sb is also used as an appropriate item for evaluating the effectiveness of therapeutic drugs targeting the early stages of ad.

 

lecanemab treatment met the primary endpoint and reduced clinical decline on the global cognitive and functional scale, cdr-sb, compared with placebo at 18 months by 27%, which represents a treatment difference in the score change of -0.45 (p=0.00005) in the analysis of intent-to-treat (itt) population. starting as early as six months, across all time points, the treatment showed highly statistically significant changes in cdr-sb from baseline compared to placebo (all p-values are less than 0.01). all key secondary endpoints were also met with highly statistically significant results compared with placebo (p<0.01). key secondary endpoints were the change from baseline at 18 months compared with placebo of treatment in amyloid levels in the brain measured by amyloid positron emission tomography (pet), the ad assessment scale-cognitive subscale14 (adas-cog14), ad composite score (adcoms) and the ad cooperative study-activities of daily living scale for mild cognitive impairment (adcs mci-adl).

 

the incidence of amyloid-related imaging abnormalities-edema/effusion (aria-e), an adverse event associated with anti-amyloid antibodies, was 12.5% in the lecanemab group and 1.7% in the placebo group. the incidence of symptomatic aria-e was 2.8% in the lecanemab group and 0.0% in the placebo group. the aria-h (aria cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis) rate was 17.0% in the lecanemab group and 8.7% in the placebo group. the incidence of symptomatic aria-h was 0.7% in the lecanemab group and 0.2% in the placebo group. there was no imbalance in isolated aria-h (i.e., aria-h in patients who did not also experience aria-e) between lecanemab (8.8%) and placebo (7.6%). the total incidence of aria (aria-e and/or aria-h) was 21.3% in the lecanemab group and 9.3% in the placebo group. overall, lecanemab’s aria incidence profile was within expectations.

 

clarity ad was a global confirmatory phase 3 placebo-controlled, double-blind, parallel-group, randomized study in 1,795 people with early ad. the treatment group was administered a dosage of 10 mg/kg bi-weekly of lecanemab, with participants allocated in a 1:1 ratio to receive either placebo or lecanemab. the baseline characteristics of both placebo and lecanemab groups are similar and well balanced. eligibility criteria allowed patients with a broad range of comorbidities/comedications: hypertension, diabetes, heart disease, obesity, renal disease and anti-coagulants, etc. eisai’s recruitment strategy for the clarity ad clinical trial ensured greater inclusion of ethnic and racial populations in the u.s., resulting in approximately 25% of the total u.s. enrollment including hispanic and african american persons living with early ad. due to the inclusive eligibility criteria and the successful recruitment of diverse ethnic and racial populations in the u.s., clarity ad’s population is generally comparable to the country’s medicare population.

 

“since eisai launched aricept in the u.s. and japan in the late 1990s and obtained its approval in over 100 countries, eisai has provided the drug to people living with dementia while building empathy for them and their families through disease education efforts and community involvement. the positive result of the lecanemab, an anti-aβ protofibril antibody, pivotal study after almost 25 years since aricept’s launch is an important milestone for eisai in fulfilling our mission to meet the expectations of the alzheimer’s disease community. alzheimer’s disease not only presents a great challenge for patients and their families, but it also negatively impacts society, including decreased productivity, increased social costs and disease-related anxiety. we believe that helping to alleviate these burdens will positively impact society as a whole,” said haruo naito, chief executive officer at eisai. “additionally, the lecanemab clarity ad study results prove the amyloid hypothesis, in which the abnormal accumulation of aβ in the brain is one of the main causes of alzheimer’s disease, when targeted with a protofibril-binding therapy. eisai believes these findings will create new horizons in the diagnosis and treatment of alzheimer’s disease as well as further activate innovation for new treatment options. the successful results of the clarity ad clinical trial would not be possible without the truly inspiring dedication of the study’s participants, their families and caregivers and the clinical investigators around the world. we thank all the people involved in the study for their invaluable contributions.”

 

“today’s announcement gives patients and their families hope that lecanemab, if approved, can potentially slow the progression of alzheimer’s disease, and provide a clinically meaningful impact on cognition and function,” said michel vounatsos, chief executive officer at biogen. “importantly, the study shows that removal of aggregated amyloid beta in the brain is associated with a slowing of disease in patients at the early stage of the disease. we want to thank the many patients who participated in this groundbreaking global study and want to acknowledge the clinical investigators who worked tirelessly to increase the enrollment of traditionally underrepresented populations. as pioneers in neuroscience, we believe defeating this disease will require multiple approaches and treatment options, and we look forward to continuing the discussion about the significance of these findings with the patient, scientific, and medical communities.”

 

in july 2022, the u.s. food and drug administration (fda) accepted eisai’s biologics license application (bla) for lecanemab under the accelerated approval pathway and granted priority review. the prescription drugs user fee act action date (pdufa) is set for january 6, 2023. the fda has agreed that the results of clarity ad can serve as the confirmatory study to verify the clinical benefit of lecanemab. in an effort to secure traditional fda approval for lecanemab as soon as possible, eisai submitted the bla through the fda’s accelerated approval pathway so that the agency could complete its review of all lecanemab data with the exception of the data from the confirmatory clarity ad study.

 

in march 2022, eisai began submitting application data, with the exception of clarity ad data, to japan’s pharmaceuticals and medical devices agency (pmda) under the prior assessment consultation system with the aim of obtaining early approval for lecanemab so that people living with early ad may have access to the therapy as soon as possible.

 

eisai serves as the lead of lecanemab development and regulatory submissions globally with both eisai and biogen co-commercializing and co-promoting the product and eisai having final decision-making authority.

findings to be featured in a late-breaking proffered paper session at european society for medical oncology (esmo) congress 2022

 

tokyo and rahway, n.j., september 12, 2022 – eisai (headquarters: tokyo, ceo: haruo naito, “eisai”) and merck & co., inc., rahway, nj, usa (known as msd outside of the united states and canada) today announced the first presentation of results from the final analysis of the phase 3 leap-002 trial investigating lenvima^®, the orally available multiple receptor tyrosine kinase inhibitor discovered by eisai, plus keytruda^®, the anti-pd-1 therapy from merck & co., inc., rahway, nj, usa versus lenvima monotherapy, as a first-line treatment for patients with unresectable hepatocellular carcinoma (uhcc). results are being presented during a proffered paper session at the european society for medical oncology (esmo) congress 2022, being held in paris, france and virtually from sept. 9-13 (abstract #lba34).

in the final analysis of the trial, there was a trend toward improvement for one of the study’s dual primary endpoints, overall survival (os), for patients treated with lenvima plus keytruda versus lenvima monotherapy; however, the results did not meet statistical significance per the pre-specified statistical plan (hr=0.84 [95% ci: 0.71-1.00]; p=0.0227). the median os was 21.2 months (95% ci: 19.0-23.6) for lenvima plus keytruda and 19.0 months (95% ci: 17.2-21.7) for lenvima monotherapy. additionally, treatment with lenvima plus keytruda resulted in a trend toward improvement in the trial’s other dual primary endpoint of progression-free survival (pfs) versus lenvima monotherapy; however, the results did not meet the pre-specified threshold at the first interim analysis for statistical significance (hr=0.87 [95% ci: 0.73-1.02]; p=0.0466).

 

“the leap-002 trial reflects our research strategy to build on evolving standards of care to further improve outcomes for more people with unresectable hepatocellular carcinoma,” said dr. gregory lubiniecki, vice president, global clinical development, merck & co., inc., rahway, nj, usa research laboratories. “the median overall survival of 21.2 months seen with keytruda plus lenvima provides critical insights for further research into the potential role of this combination.”

“while the outcome is not what we had hoped, it is important for us to see that patients in the trial treated with lenvima monotherapy had a median overall survival of 19.0 months,” said corina dutcus, m.d., senior vice president, clinical research, oncology at eisai inc. “findings from the leap-002 trial will not only help advance our understanding and application of lenvima plus keytruda across our clinical development program but will also provide physicians with additional information on lenvima monotherapy’s use in unresectable hepatocellular carcinoma, where it is currently approved as a treatment option in multiple regions around the world, including the u.s., the european union (eu), japan and china.”

lenvima monotherapy is approved for the first-line treatment of patients with uhcc in the u.s., the eu and china and for patients with uhcc in japan. the approval of lenvima was based on results of the phase 3 reflect trial, which evaluated the efficacy and safety of lenvima versus sorafenib for the first-line treatment of patients with uhcc.

lenvima (marketed as kisplyx^® for renal cell carcinoma [rcc] in the eu) plus keytruda is approved in the u.s., the eu and japan for the treatment of certain types of advanced endometrial carcinoma and advanced rcc. eisai and merck & co., inc., rahway, nj, usa are studying the lenvima plus keytruda combination through the leap (lenvatinib and pembrolizumab) clinical program in multiple tumor types, including but not limited to endometrial carcinoma, hcc, melanoma, non-small cell lung cancer, rcc, head and neck cancer, colorectal cancer, gastric cancer and esophageal cancer, across more than 15 clinical trials.

 

leap-002 study design and final analysis results (abstract #lba34)

leap-002 is a multicenter, randomized, double-blinded, active-controlled phase 3 trial (clinicaltrials.gov, ) evaluating lenvima plus keytruda versus lenvima monotherapy for the first-line treatment of adult patients with uhcc. patients were randomized 1:1 to receive lenvima (12 mg orally once daily [for patients with screening body weight of at least 60 kg] or 8 mg orally once daily [for patients with screening body weight less than 60 kg]) plus keytruda (200 mg intravenously [iv] on day 1 of each three-week cycle); or lenvima (12 mg orally once daily [for patients with screening body weight of at least 60 kg] or 8 mg orally once daily [for patients with screening body weight less than 60 kg]) plus saline placebo (iv administered on day 1 of each three-week cycle). lenvima was administered until progressive disease or unacceptable toxicity. keytruda/placebo was administered for up to 35 cycles (approximately two years).

the dual primary endpoints were pfs, as assessed by blinded independent central review (bicr) per response evaluation criteria in solid tumors version 1.1 (recist v1.1; recist v1.1 has been modified for this study to follow a maximum of 10 target lesions in total and a maximum of five target lesions per organ), and os. objective response rate (orr), as assessed by bicr per recist v1.1, was a key secondary endpoint. the trial was designed with two interim analyses and a final analysis for os. pre-specified efficacy boundaries were one-sided p=0.002 for pfs at interim analysis 1 and p=0.0185 for os at the final analysis.

as of the data cut-off for the final analysis (june 21, 2022), a total of 794 patients were enrolled and treated, with a median follow-up of 32.1 months (range, 25.8-41.1). a total of 534 os events had occurred, with 36 patients (9.1%) in the combination arm and 24 patients (6.1%) in the lenvima monotherapy arm remaining on study treatment.

the median os was 21.2 months (95% ci: 19.0-23.6) for lenvima plus keytruda versus 19.0 months (95% ci: 17.2-21.7) for lenvima monotherapy at the final analysis. the median pfs was 8.2 months (95% ci, 6.4-8.4) for lenvima plus keytruda versus 8.0 months (95% ci: 6.3-8.2) for lenvima monotherapy at the first interim analysis and 8.2 months (95% ci: 6.3-8.3) versus 8.1 months (95% ci: 6.3-8.3), respectively, at the final analysis. the orr was 26.1% (95% ci: 21.8-30.7) for lenvima plus keytruda versus 17.5% (95% ci: 13.9-21.6) for lenvima monotherapy at the final analysis. median duration of response was 16.6 months (range, 2.0 to 33.6 ) in the keytruda plus lenvima arm versus 10.4 months (range, 1.9 to 35.1 ) in the lenvima monotherapy arm at the final analysis.

the safety profile of lenvima plus keytruda was consistent with previously reported data on the combination. grade 3-4 treatment-related adverse events (traes) occurred in 61.5% of patients treated with lenvima plus keytruda versus 56.7% of patients treated with lenvima monotherapy. grade 5 traes occurred in 1.0% of patients treated with lenvima plus keytruda versus 0.8% of patients treated with lenvima monotherapy. in patients treated with lenvima plus keytruda, the five most common traes of any grade were hypertension (43.3%), diarrhea (40.3%), hypothyroidism (40.0%), palmar-plantar erythrodysesthesia (ppe) syndrome (33.2%) and proteinuria (30.6%). in patients treated with lenvima monotherapy, the five most common traes of any grade were hypertension (46.8%), hypothyroidism (35.7%), proteinuria (34.9%), diarrhea (33.9%) and ppe syndrome (30.6%). post-study systematic anti-cancer treatments were given for 44.1% of patients receiving lenvima plus keytruda versus 52.1% of those receiving lenvima monotherapy.

 

 

eisai co., ltd.

 

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

eisai co., ltd. (headquarters: tokyo, ceo: haruo naito, “eisai”) announced today that it has filed a supplementary new drug application in japan for its in-house discovered antiepileptic drug (aed) fycompa^® (perampanel) seeking approval for an injection formulation as a new route of administration.

fycompa is a first-in-class aed discovered at eisai’s tsukuba research laboratories. the agent is a highly selective, noncompetitive ampa receptor antagonist that is postulated to reduce neuronal hyper-excitation associated with seizures by targeting glutamate activity at ampa receptors on postsynaptic membranes. two oral formulations of fycompa are available in japan: a tablet and a fine granule formulation. due to concern about the risks associated with interruption of administration when the drug cannot be taken orally temporarily, such as during surgery, it is suggested that epilepsy patients should continue treatment other than via oral administration. the injection formulation was developed as a non-oral administration route to meet such medical needs, and its bioequivalence to the tablet formulation, as well as the confirmation of the safety and tolerability of the injection formulation when administered as an alternative therapy to the tablet, lead to this application. the addition of an injection formulation of fycompa, the only ampa receptor antagonist-based aed, to the product lineup is expected to provide a new treatment option for a broader range of patients.

it is estimated that there are approximately 1 million patients with epilepsy in japan, and although onset occurs at any age, it is most common in people aged 18 and younger, and the elderly.

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

 

media inquiries:

public relations department,

eisai co., ltd.

81-(0)3-3817-5120