by codm | Apr 3, 2023 | Newsletter
For Print(PDF)
Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has entered into an agreement with the National Cancer Center to collaborate on investigator-initiated clinical research for the EZH2 inhibitor tazemetostat hydrobromide (generic name, product name “Tazverik® Tablets 200 mg”, “tazemetostat”) based on “Patient-Proposed Healthcare Services” system. This clinical research will be conducted by the National Cancer Center Hospital.
The “Patient-Proposed Healthcare Services” system is a system under which medical treatment using unapproved drugs not covered by insurance is applied for to the government based on the patient’s request, and is conducted as a clinical trial to confirm safety and efficacy. Under the terms of the agreement, Eisai will provide tazemetostat free of charge to the National Cancer Center Hospital as the drug to be used in “A clinical trial of Tazemetostat for pediatric and AYA* patients with malignant tumors which have no standard of care or and which is refractory to standard of care: Patients-Proposed Healthcare Service” to be conducted by the hospital under this program.
Researched and developed by Eisai and Epizyme, Inc.,** an Ipsen (Headquarters: France) company, tazemetostat is a first-in-class, oral small molecule inhibitor of the epigenetic enzyme EZH2. It is one of the histone methyltransferases in the epigenetics-related protein group, and is thought to regulate the expression of cancer-related genes and suppress the growth of cancer cells by specifically targeting EZH2, which contributes to the cancer growth process.1 Eisai holds the rights for development and commercialization of tazemetostat in Japan, where it was approved for the indication of “relapsed or refractory EZH2 gene mutation-positive follicular lymphoma (only when standard treatment is not applicable)” in 2021, and manufactures and distributes the product.
Eisai positions oncology as a key franchise area and aims to create innovative drugs that act towards curing cancer. Eisai is committed to expanding the potential clinical benefits of tazemetostat for cancer treatment, as it seeks to contribute to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families and healthcare professionals.
* AYA (Adolescent & Young Adult): Patients between the ages of 15 and 39.
** Acquired by Ipsen in 2022
Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120
[Notes to editors]
1. About the “Patient-Proposed Healthcare Services” system
The “Patient-Proposed Healthcare Services” system is a system that allows patients who wish to use unapproved drugs and other medications as uninsured treatment to do so promptly, based on the patient’s request, while confirming the safety and efficacy of the drug and allowing access to the unapproved drugs at medical institutions close by. The objective is to accumulate data and scientific evidence for future insurance coverage.
Ministry of Health, Labour and Welfare “Patient-Proposed Healthcare Services” (Moushide Ryouyou) System: https://www.mhlw.go.jp/moushideryouyou/ (Japanese only)
2. About tazemetostat hydrobromide (generic name, product name “Tazverik® Tablets 200 mg”)
Tazemetostat is a first-in-class, oral small molecule inhibitor that targets EZH2 that was jointly researched and developed under the alliance agreement between Eisai and Epizyme, Inc., an Ipsen company, utilizing Epizyme, Inc.’s proprietary product platform. This agent selectively inhibits EZH2 in a competitive matter with S-adenosylmethionine (a methyl group donor) to suppress methylation of H3K27.1 Eisai is responsible for development and commercialization of this agent in Japan, where the drug was approved in June 2021 for the indication of “relapsed or refractory EZH2 gene mutation-positive follicular lymphoma (only when standard treatment is not applicable)”. Ipsen is responsible for the development and commercialization of this agent in the United States, where accelerated approval was granted for in January 2020 with the indication of “adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection”. In June of the same year, the accelerated approval was granted for this agent with the indication of “adult relapsed / refractory follicular lymphoma who had at least 2 regimens of prior treatment and whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test”, and of “adult relapsed / refractory follicular lymphoma for which there are no satisfactory alternative treatment options”. This agent is not approved outside of Japan and the United States.
3. About epigenetics
Epigenetics is a branch of science that studies the mechanism for the acquired activation/inactivation of gene function and seeks to determine how gene function is inherited through cell division, irrespective of DNA base sequence alteration. Examples of modification that lead to the regulation of gene expression include methylation of DNA and modifications of histone (methylation, acetylation, phosphorylation, etc.).
4. About EZH2
EZH2 is one of the histone methyltransferases within a larger class of epigenetics-related proteins, and specifically catalyzes the methylation of histone H3 at lysine 27 (H3K27), thus controlling expression of various genes. It is indicated that an increase in methylation of H3K27 caused by EZH2 gain-of-function mutation, overexpression, or the dysfunction of the SWI/SNF (switch/sucrose non-fermenting) complex that reportedly inhibits EZH2 methylation activity, plays an important role in carcinogenesis.1
1 Sarah K. Knutson, Satoshi Kawano, Yukinori Minoshima, et al. Selective Inhibition of EZH2 by EPZ-6438 Leads to Potent Antitumor Activity in EZH2-Mutant Non-Hodgkin Lymphoma. Molecular Cancer Therapeutics. 2014 Apr; 13(4):842–854
by codm | Mar 31, 2023 | Newsletter
For Print(PDF) (187KB）
TOKYO and CAMBRIDGE, Mass., March 31, 2023 – Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Christopher A. Viehbacher, “Biogen”) announced today that Eisai presented new analyses on amyloid-related imaging abnormalities (ARIA) with the use of antiplatelet and anticoagulant medications, isolated ARIA-H, and caregiver burden and health-related quality of life (QOL), from the results of Eisai’s Phase 3 Clarity AD study of lecanemab (generic name, U.S. brand name: LEQEMBI™), an anti-amyloid-β (Aβ) protofibril* antibody, at the 2023 International Conference on Alzheimer’s and Parkinson’s Diseases annual meeting AD/PD™.
Clarity AD was a global confirmatory Phase 3 placebo-controlled, double-blind, parallel-group, randomized study in 1,795 people with early Alzheimer’s disease (AD) (lecanemab group: 10 mg/kg bi-weekly IV treatment: 898, placebo group: 897). Lecanemab met the primary endpoint and all key secondary endpoints with highly statistically significant results. In November 2022, results of the Clarity AD study were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference and simultaneously published in the peer-reviewed medical journal, The New England Journal of Medicine.
1. Lecanemab Phase 3 Clarity AD Trial: ARIA With the Use of Antiplatelets or Anticoagulants in Early Alzheimer’s Disease
In the Clarity AD study, ARIA rates were higher for patients receiving lecanemab compared to those on placebo. The objective of this analysis was to evaluate antiplatelet and anticoagulant medication use in participants who experienced either ARIA-E (edema) or ARIA-H (combined cerebral microhemorrhages, superficial siderosis, and intracerebral hemorrhages >1 cm in diameter).
The risks of ARIA appear slightly higher in the placebo group with antiplatelet or with anticoagulants relative to placebo subjects not on anticoagulants (no antiplatelet or anticoagulation: 8.9%, antiplatelet: 9.7%, anticoagulation (anticoagulation alone or with antiplatelet): 10.8%). ARIA rates may be slightly lower in those on lecanemab treated with antiplatelet or with anticoagulation, relative to lecanemab treated subjects not with antiplatelet or with anticoagulation (no antiplatelet or anticoagulation: 21.8%, antiplatelet: 17.9%, anticoagulation: 13.3%).
The incidence of ARIA-E was 13.1% in the lecanemab group and 1.5% in the placebo group when no antiplatelet or anticoagulant medication was used, 10.4% in the lecanemab group and 0.84% in the placebo group when antiplatelet medication was used, and 4.8% in the lecanemab group and 2.7% in the placebo group when anticoagulant medication was used.
Because intracerebral hemorrhage >1cm have been observed in patients taking lecanemab, additional caution should be exercised when considering administration of antithrombotics or a thrombolytic agent.
In Clarity AD, ARIA did not occur more frequently in lecanemab-treated participants on antiplatelet or anticoagulant drugs compared to lecanemab-treated participants that were not on either.
2. Isolated ARIA-H in Patients Treated with Lecanemab in the Phase 3 Clarity AD Study in Early Alzheimer’s Disease
The objective of this analysis was to describe the occurrences and timing of isolated ARIA-H events (i.e., those events not occurring temporally concurrent with ARIA-E). The incidence of overall ARIA-H was 17.3% in the lecanemab group and 9.0% in the placebo group, and the incidence of isolated ARIA-H was similar in the lecanemab (8.9%) and placebo (7.8%) groups in Clarity AD. While ARIA-H concurrent with ARIA-E occurred early in the treatment as expected given timing of ARIA-E, isolated ARIA-H in both the placebo and lecanemab groups were infrequent and occurred at a steady rate over 18 months of treatment. The incidence of isolated ARIA-H increased with number of ApoEε4 alleles in both placebo (noncarriers: 3.8%; heterozygotes: 7.3%; homozygotes: 18.0%), and lecanemab group (noncarriers: 8.3%; heterozygotes: 8.4%; homozygotes: 12.1%). On the other hand, it was found that the ApoEε4 carrier status did not impact the timing of overall occurrence of ARIA-H.
In Clarity AD, the pattern of occurrence of isolated ARIA-H in lecanemab group was similar to that in placebo group.
3. Lecanemab Clarity AD: Quality-of-Life Results from a Randomized, Double-Blind Phase 3 Trial in Early Alzheimer’s Disease
The objective of this analysis was to describe the health-related quality-of-life (HRQoL) pre-specified exploratory results from Clarity AD. HRQoL by subject was measured using the European Quality of Life–5 Dimensions (EQ-5D-5L**) and Quality of Life in AD (QOL-AD***) scales at baseline and every 6 months post-baseline. QOL-AD was also assessed for the subject by the care partner. Additionally, care partners were administered the Zarit Burden Interview**** every 6 months to assess care partner burden associated with dementia.
At month 18, adjusted mean change from baseline in EQ-5D-5L and QOL-AD of subject showed 49% and 56% less decline, respectively. Care partner burden measured Zarit Burden Interview and QOL-AD by partner resulted in 38% and 23% less decline at 18 months, respectively. Assessment results were consistent across ApoE genotypes.
The results of the Clarity AD Health-related QoL measures presented additional evidence for meaningful benefits of lecanemab treatment to patients and care partners.
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.
* Protofibrils are large Aβ aggregated soluble species of 75-5000 Kd.1
** The European Quality of Life-5 Dimensions (EQ-5D-5L) is used as a patient-reported measure of quality of life and consists of five domains (degree of mobility, personal care, daily living, pain/discomfort and anxiety/blushing).
*** Quality of Life in AD (QOL-AD) is a quality-of-life index specific to dementia.
**** The Zarit Burden Interview is a scale to measure caregiver burden.
References
1 Söderberg, L., Johannesson, M., Nygren, P. et al. Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease. Neurotherapeutics (2022). https://doi.org/10.1007/s13311-022-01308-6. Accessed March 23, 2023
Media Contacts:
| Eisai |
Biogen Inc. |
|
Eisai Co., Ltd.
Public Relations Department
Eisai Inc. (U.S.)
Libby Holman
Eisai Europe, Ltd.
(Europe, Australia, New Zealand and Russia)
EMEA Communications Department
|
Natacha Gassenbach
+ 1-857-777-6573
public.affairs@biogen.com |
Investor Contacts:
| Eisai Co., Ltd. |
Biogen Inc. |
Investor Relations Department
|
Mike Hencke
|
[Notes to Editors]
About Lecanemab
Lecanemab (brand name in the U.S.: LEQEMBI™) is the result of a strategic research alliance between Eisai and BioArctic. Lecanemab is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). In the U.S., LEQEMBI was granted accelerated approval by the U.S. Food and Drug Administration (FDA) on January 6, 2023. LEQEMBI is indicated for the treatment of Alzheimer’s disease (AD) in the U.S. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved in the U.S. under Accelerated Approval based on reduction in Aβ plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
Please see full Prescribing Information in the United States.
The Clarity AD study of lecanemab met its primary endpoint and all key secondary endpoints with highly statistically significant results. In the U.S., Eisai submitted a supplemental Biologics License Application (sBLA) to the FDA for approval under the traditional pathway on January 6, 2023. On March 3, 2023, the FDA accepted Eisai’s sBLA based on the Clarity AD clinical data, and the LEQEMBI application has been granted Priority Review, with a Prescription Drug User Fee Act (PDUFA) action date of July 6, 2023. The FDA is currently planning to hold an Advisory Committee to discuss this application but has not yet publicly announced the date of the meeting. Eisai submitted an application for manufacturing and marketing approval to the Pharmaceuticals and Medical Devices Agency (PMDA) on January 16, 2023, in Japan. The Priority Review was granted by the Ministry of Health, Labour and Welfare (MHLW) on January 26, 2023. Eisai utilized the prior assessment consultation system of PMDA, with the aim of shortening the review period for lecanemab. In Europe, Eisai submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) on January 9, 2023, and accepted on January 26, 2023. In China, Eisai initiated submission of data for a BLA to the National Medical Products Administration (NMPA) of China in December 2022, and the Priority Review was granted on February 27, 2023.
Eisai has completed lecanemab subcutaneous bioavailability study, and subcutaneous dosing is currently being evaluated in the Clarity AD (Study 301) OLE.
Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer’s Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen.
Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing.
About the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market lecanemab for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody lecanemab back-up was signed in May 2015.
About Eisai Co., Ltd.
Eisai’s Corporate Concept is “to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides.” Under this concept (also known as the human health care [hhc] concept), we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of neurology and oncology. In addition, we demonstrate our commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), by working on various activities together with global partners. For more information about Eisai, please visit www.eisai.com (for global headquarters: Eisai Co., Ltd.), and connect with us on Twitter @Eisai_SDGs
.
About Biogen
Founded in 1978, Biogen is a leading global biotechnology company that has pioneered multiple breakthrough innovations including a broad portfolio of medicines to treat multiple sclerosis, the first approved treatment for spinal muscular atrophy, and two co-developed treatments to address a defining pathology of Alzheimer’s disease. Biogen is advancing a pipeline of potential novel therapies across neurology, neuropsychiatry, specialized immunology and rare diseases and remains acutely focused on its purpose of serving humanity through science while advancing a healthier, more sustainable and equitable world.
The company routinely posts information that may be important to investors on its website at www.biogen.com. Follow Biogen on social media – Twitter, LinkedIn, Facebook, YouTube.
Biogen Safe Harbor
This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, about the potential clinical effects of lecanemab; the potential benefits, safety and efficacy of lecanemab; potential regulatory discussions, submissions and approvals and the timing thereof; the treatment of Alzheimer’s disease; the anticipated benefits and potential of Biogen’s collaboration arrangements with Eisai; the potential of Biogen’s commercial business and pipeline programs, including lecanemab; and risks and uncertainties associated with drug development and commercialization. These statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “possible,”” “potential,” “will,” “would” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. You should not place undue reliance on these statements or the scientific data presented.
These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation unexpected concerns that may arise from additional data, analysis or results obtained during clinical studies, including the Clarity AD clinical trial and AHEAD 3-45 study; the occurrence of adverse safety events; risks of unexpected costs or delays; the risk of other unexpected hurdles; regulatory submissions may take longer or be more difficult to complete than expected; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of Biogen’s drug candidates, including lecanemab; actual timing and content of submissions to and decisions made by the regulatory authorities regarding lecanemab; uncertainty of success in the development and potential commercialization of lecanemab; failure to protect and enforce Biogen’s data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; third party collaboration risks; and the direct and indirect impacts of the ongoing COVID-19 pandemic on Biogen’s business, results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Biogen’s expectations in any forward-looking statement. Investors should consider this cautionary statement as well as the risk factors identified in Biogen’s most recent annual or quarterly report and in other reports Biogen has filed with the U.S. Securities and Exchange Commission. These statements are based on Biogen’s current beliefs and expectations and speak only as of the date of this news release. Biogen does not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.
by codm | Mar 31, 2023 | Newsletter
For Print(PDF)
TOKYO and CAMBRIDGE, Mass., March 31, 2023 – Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Christopher A. Viehbacher, “Biogen”) announced today that three additional detailed analyses from the Phase IIb clinical study (Study 201), evaluating the efficacy and safety of lecanemab for mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD (collectively known as early AD), were published in the peer-reviewed journals.
- Detailed results on biomarker, cognitive, and clinical effects from Study 201 core to OLE (open-label extension): Alzheimer’s Research and Therapy
- Consistency of efficacy results across various clinical measures and statistical methods in Study 201: Alzheimer’s Research and Therapy
- ARIA (amyloid-related imaging abnormality) profile in Study 201: Alzheimer’s & Dementia: Translational Research and Clinical Interventions
Study 201 was a multicenter, double-blind, placebo-controlled, Phase 2b trial conducted in 856 patients with early AD. Its core study evaluated key efficacy assessments, including clinical change on the AD Composite Score (ADCOMS) as the primary endpoint at 12 months and as key secondary endpoints, ADCOMS, Clinical Dementia Rating-Sum-of-Boxes (CDR-SB) and AD Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14) at 18 months. Following analysis of the 18-month core phase, an intervening off-treatment period (gap period) ranging from 9-59 months (mean 24 months) was taken, which was followed by an OLE with 10 mg/kg IV bi-weekly lecanemab dosing to assess long-term safety and tolerability. The results of the primary analysis in the core study including clinical efficacy and biomarkers have already been published, showing a consistent reduction in clinical decline across several clinical and biomarker endpoints with lecanemab 10 mg/kg bi-weekly dosing.
1. Detailed results on biomarker, cognitive, and clinical effects from Study 201.
“Lecanemab in patients with early Alzheimer’s disease: detailed results on biomarker, cognitive, and clinical effects from the randomized and open‑label extension of the phase 2 proof‑of‑concept study”
In the core 201 study, lecanemab was shown to reduce brain Aβ accumulation measured by amyloid PET in a dose- and time-dependent manner after 12 and 18 months of treatment, and corresponding changes in plasma biomarkers and reduction in clinical decline. During the gap period, a trend was observed for plasma Aβ42/40 ratio and p-tau181 values to return to the pre-administration levels (re-accumulation) faster than amyloid PET.
In the OLE, lecanemab 10 mg/kg biweekly treatment showed a decrease in brain amyloid beta (Aβ) accumulation measured by amyloid PET, a decrease in the plasma Aβ42/40 ratio, and a decrease in plasma p-tau181.
The potential for disease modification with lecanemab is supported by an increasing difference in clinical measures between the lecanemab group and placebo group in line with time during the core period, differences in clinical progression between subjects who received 10 mg/kg lecanemab and those who received placebo in the core period, which remained persistent throughout the gap period, and an impact on biological measures that reflect key pathophysiological changes in AD. Furthermore, the results showed the potential for monitoring the treatment effects of lecanemab using plasma biomarkers.
2. Consistency of efficacy results across various clinical measures and statistical methods in Study 201.
“Consistency of efficacy results across various clinical measures and statistical methods in the lecanemab phase 2 trial of early Alzheimer’s disease”
In order to assess the robustness of lecanemab’s efficacy in Study 201, sensitivity analyses were performed using several statistical models for three key clinical endpoints (ADCOMS, CDR-SB, ADAS-Cog14). The sensitivity analysis showed that 18 months of lecanemab treatment consistently reduced the clinical decline in all statistical models examined. The results of all sensitivity analyses for three key clinical endpoints at the highest dose (10 mg/kg bi-weekly) at 18 months were consistent, with a 29.1% to 37.4% reduction in clinical deterioration with lecanemab compared to placebo for ADCOMS, 26.5% to 38.4% for CDR-SB and 37.4% to 55.9% for ADAS-Cog14.
3. ARIA profile in Study 201
“ARIA in patients treated with lecanemab (BAN2401) in a phase 2 study in early Alzheimer’s disease”
In the core study 201, amyloid-related imaging abnormalities-edema (ARIA-E) was dose dependent, with an incidence 9.9% at the highest doses (10 mg/kg bi-weekly) for the overall population and 14.3% for ApoE4 positive subjects. Most ARIA-E occurred within 30 days after the initial dose and had mild to moderate severity in radiographic severity. Symptomatic ARIA-E occurred in 3% of participants in the 10mg/kg bi-weekly treatment group. ARIA cerebral microhemorrhages, intracerebral hemorrhage >1cm, and superficial siderosis (ARIA-H) occurred in 6.2% of subjects who received 10 mg/kg biweekly lecanemab and those events were mostly mild in severity. There were no symptomatic cases of ARIA-H reported in the core study.
Overall ARIA-E events in the OLE phase were generally consistent with the rate seen in the lecanemab 10 mg/kg biweekly group in the core study (four subjects treated with placebo in the core study had ARIA-E in the OLE (4 of 45: 8.9%). As with the core study, most ARIA-E occurred within 3 months after receiving the initial dose in the OLE and had mostly mild to moderate in radiographic severity. ARIA-H events in the OLE were generally consistent with the rate seen in the lecanemab 10 mg/kg biweekly group in the core study. ARIA-H events were mostly mild or moderate in severity. One symptomatic case of ARIA-H, intracerebral hemorrhage > 1cm, was reported in OLE. This subject did not have concurrent ARIA-E, and the adverse event resolved with residual visual field defect.
PK/PD modeling showed that the incidence of ARIA-E was correlated with Cmax at steady state.
Based on the fact that lecanemab was generally well tolerated at the highest dose in this study, the Phase 3 Clarity AD study was conducted without dose titration. A subcutaneous formulation that may potentially reduce the Cmax of lecanemab is being developed and evaluated to determine if there is a reduction of the incidence of ARIA-E compared to intravenous formulation.
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.
To learn more, visit www.LEQEMBI.com.
Media Contacts:
| Eisai |
Biogen Inc. |
|
Eisai Co., Ltd.
Public Relations Department
Eisai Inc. (U.S.)
Libby Holman
Eisai Europe, Ltd.
(Europe, Australia, New Zealand and Russia)
EMEA Communications Department
|
Natacha Gassenbach
+ 1-857-777-6573
public.affairs@biogen.com |
Investor Contacts:
| Eisai Co., Ltd. |
Biogen Inc. |
Investor Relations Department
|
Mike Hencke
|
[Notes to Editors]
1. About Lecanemab
Lecanemab (Brand Name in the U.S.: LEQEMBI™) is the result of a strategic research alliance between Eisai and BioArctic. Lecanemab is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). Lecanemab selectively binds and eliminates Aβ protofibrils that are thought to contribute to the neurotoxicity in AD. As such, lecanemab may have the potential to have an effect on disease pathology and to slow down the progression of the disease. LEQEMBI is indicated for the treatment of Alzheimer’s disease (AD) in the U.S. under an accelerated approval by the U.S. Food and Drug Administration (FDA). Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in Aβ plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial. The Clarity AD study of lecanemab met its primary endpoint and all key secondary endpoints with highly statistically significant results.
Please see full Prescribing Information in the United States.
Lecanemab-irmb was approved under the accelerated approval pathway in the U.S. and was launched in the U.S. on January 18, 2023. The accelerated approval was based on Phase 2 data that demonstrated that lecanemab reduced the accumulation of Aβ plaque in the brain, a defining feature of AD, and its continued approval may be contingent upon verification of lecanemab’s clinical benefit in a confirmatory trial. The FDA determined that the results of the Phase 3 Clarity AD study can serve as the confirmatory study to verify the clinical benefit of lecanemab. In November 2022, the results of Clarity AD study were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference and simultaneously published in the peer-reviewed medical journal, The New England Journal of Medicine.
In the U.S., Eisai submitted a supplemental Biologics License Application (sBLA) to the FDA for approval under the traditional pathway on January 6, 2023. On March 3, 2023, the FDA accepted Eisai’s sBLA based on the Clarity AD clinical data, and the lecanemab application has been granted Priority Review, with a Prescription Drug User Fee Act (PDUFA) action date of July 6, 2023. The FDA is currently planning to hold an Advisory Committee to discuss this application but has not yet publicly announced the date of the meeting. Eisai submitted an application for manufacturing and marketing approval to the Pharmaceuticals and Medical Devices Agency (PMDA) on January 16, 2023, in Japan. The Priority Review was granted by the Ministry of Health, Labour and Welfare (MHLW) on January 26, 2023. Eisai utilized the prior assessment consultation system of PMDA, with the aim of shortening the review period for lecanemab. In Europe, Eisai submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) on January 9, 2023, which was accepted on January 26, 2023. In China, Eisai initiated submission of data for a BLA to the National Medical Products Administration (NMPA) of China in December 2022, and the Priority Review was granted on February 27, 2023 .
Eisai has completed a lecanemab subcutaneous bioavailability study, and subcutaneous dosing is currently being evaluated in the Clarity AD OLE.
Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, has been ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer’s Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S., funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen.
Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, has been ongoing.
2. About the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
3. About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market LEQEMBI for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody LEQEMBI back-up was signed in May 2015.
4. About Eisai Co., Ltd.
Eisai’s Corporate Concept is “to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides.” Under this concept (also known as the human health care [hhc] concept), we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of neurology and oncology.
In addition, we demonstrate our commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), by working on various activities together with global partners.
For more information about Eisai, please visit www.eisai.com (for global headquarters: Eisai Co., Ltd.), and connect with us on Twitter @Eisai_SDGs.
5. About Biogen
Founded in 1978, Biogen is a leading global biotechnology company that has pioneered multiple breakthrough innovations including a broad portfolio of medicines to treat multiple sclerosis, the first approved treatment for spinal muscular atrophy, and two co-developed treatments to address a defining pathology of Alzheimer’s disease. Biogen is advancing a pipeline of potential novel therapies across neurology, neuropsychiatry, specialized immunology and rare diseases and remains acutely focused on its purpose of serving humanity through science while advancing a healthier, more sustainable and equitable world.
The company routinely posts information that may be important to investors on its website at www.biogen.com. Follow Biogen on social media – Twitter, LinkedIn, Facebook, YouTube.
Biogen Safe Harbor
This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, about the potential clinical effects of lecanemab; the potential benefits, safety and efficacy of lecanemab; potential regulatory discussions, submissions and approvals and the timing thereof; the treatment of Alzheimer’s disease; the anticipated benefits and potential of Biogen’s collaboration arrangements with Eisai; the potential of Biogen’s commercial business and pipeline programs, including lecanemab; and risks and uncertainties associated with drug development and commercialization. These statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “possible,”” “potential,” “will,” “would” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. You should not place undue reliance on these statements or the scientific data presented.
These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation unexpected concerns that may arise from additional data, analysis or results obtained during clinical studies, including the Clarity AD clinical trial and AHEAD 3-45 study; the occurrence of adverse safety events; risks of unexpected costs or delays; the risk of other unexpected hurdles; regulatory submissions may take longer or be more difficult to complete than expected; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of Biogen’s drug candidates, including lecanemab; actual timing and content of submissions to and decisions made by the regulatory authorities regarding lecanemab; uncertainty of success in the development and potential commercialization of lecanemab; failure to protect and enforce Biogen’s data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; third party collaboration risks; and the direct and indirect impacts of the ongoing COVID-19 pandemic on Biogen’s business, results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Biogen’s expectations in any forward-looking statement. Investors should consider this cautionary statement as well as the risk factors identified in Biogen’s most recent annual or quarterly report and in other reports Biogen has filed with the U.S. Securities and Exchange Commission. These statements are based on Biogen’s current beliefs and expectations and speak only as of the date of this news release. Biogen does not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.
by codm | Mar 24, 2023 | Newsletter
For Print(PDF)
Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today the presentation of two abstracts at the Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer (#SGOMtg), which is taking place in-person in Tampa, Florida and virtually from March 25-28.
Notable research to be featured in the Scientific Plenary IX: The Best of the Rest session includes a presentation of real-world outcomes and healthcare resource utilization in patients with recurrent or advanced endometrial carcinoma who were rechallenged with platinum chemotherapy in Europe (Abstract: #17). Also to be presented are data from the LEAP (LEnvatinib And Pembrolizumab) clinical program analyzing tumor-response from the lenvatinib (LENVIMA®) plus pembrolizumab (KEYTRUDA®) arm of the pivotal Phase 3 Study 309/KEYNOTE-775 trial in patients with advanced endometrial carcinoma following at-least one prior platinum-based regimen in any setting (NCT03517449; Abstract: #518).
“We look forward to sharing our data at this year’s SGO Annual Meeting, particularly a new study that will be presented in an oral scientific plenary session featuring real-world outcomes in patients with recurrent or advanced endometrial cancer who were rechallenged with platinum chemotherapy,” said Dr. Takashi Owa, Chief Scientific Officer, Senior Vice President, Eisai Co., Ltd. “We believe this research is important to the healthcare providers and patients we aim to serve because it is essential to understand treatment dynamics and related outcomes in clinical practice. As a human health care company, we remain steadfast in our commitment to advance the science of cancer medicine through the generation of real-world evidence.”
In March 2018, Eisai and Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside of the United States and Canada), through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvatinib, both as monotherapy and in combination with Merck’s anti-PD-1 therapy pembrolizumab. To date, more than 10 trials have been initiated under the LEAP clinical program, which is evaluating the combination across multiple tumor types.
This release discusses investigational compounds and investigational uses for FDA-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational compounds or investigational uses of FDA-approved products will successfully complete clinical development or gain FDA approval.
The full list of Eisai presentations is included below. Full abstracts will be posted the day of scheduled presentations.
Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120
[Notes to editors]
1. Eisai’s Focus on Cancer
Eisai acknowledges “Oncology” as one of its key strategic areas, and will continue to focus on the discovery and development of anti-cancer drugs within drug discovery domains including “tumor microenvironment”, “proteostasis disruption”, “cell linage and cell differentiation”, and “inflammation, hypoxia, oxidative stress and cell senescence” under the Deep Human Biology Learning (DHBL) drug discovery and development organization. Eisai aspires to discover innovative new drugs with new targets and mechanisms of action from these domains with the aim of contributing to the cure of cancers.
* KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
by codm | Mar 23, 2023 | Newsletter
Presentations Explore ARIA with the Use of Antiplatelets or Anticoagulants and Isolated ARIA-H in Patients from Eisai’s Lecanemab Phase 3 Confirmatory Clarity AD Study in Early Alzheimer’s Disease
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Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today the company will present the latest findings on lecanemab (generic name, U.S. brand name: LEQEMBI™), Eisai’s anti-amyloid beta (Aβ) protofibril* antibody for the treatment of Alzheimer’s disease (AD), at the 2023 International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders (AD/PD™) from March 28-April 1 in Gothenburg, Sweden and virtually. Eisai will present new findings from the company’s large, global Phase III confirmatory study of lecanemab, Clarity AD, including research into the management and monitoring of amyloid-related imaging abnormalities (ARIA) and health-related quality of life (HRQoL) measures. Eisai will also host a symposium, titled “Patient Clinical Care Pathway in Alzheimer’s disease: Dialogue Amongst Experts,” which will address the evolving landscape in AD. The lecanemab data and additional research findings from Eisai’s AD portfolio will be featured in 11 presentations, including seven oral and four poster presentations.
“Our latest research examines the real-world outcomes based on lecanemab’s impact on clinical results and safety, including its effect on health-related quality of life. Through our ongoing research, we hope to help simplify the patient journey and improve the lives of those living with Alzheimer’s disease,” said Michael Irizarry, M.D., Deputy Chief Clinical Officer and Senior Vice President of Clinical Research at Eisai Inc. “In addition to lecanemab, Eisai is presenting on several other key issues that will shape the future of Alzheimer’s disease and brain health, including the next generation of clinical care and diagnostic pathways, exploration of unique populations affected by the disease, and accelerating drug development. We look forward to sharing our latest findings, including new insights from Eisai’s Clarity AD trial of lecanemab, with the scientific community at AD/PD 2023.”
Key Eisai Lecanemab and AD Presentations
- Two presentations related to ARIA in the Clarity AD trial will be presented during an oral session on Thursday, March 30:
– An analysis evaluating the use of antiplatelet and anticoagulant drugs in patients who experienced ARIA.
– An analysis of isolated ARIA-H events in the Clarity AD trial.
- Research evaluating caregiver burden and HRQoL across multiple scales using Clarity AD data will be presented during an oral session on Thursday, March 30.
- Research studying the characterization of Aβ protofibrils and the unique binding properties and mechanisms of Aβ clearance of lecanemab on Friday, March 31.
- Designing The Next Generation Clinical Care and Diagnostic Pathway for Alzheimer’s Disease: A presentation focused on a new pathway which interweaves clinical, biological and digital assessments to guide an individualized AD patient journey on Friday, March 31.
Eisai Symposium – Patient Clinical Care Pathway in AD: Dialogue Amongst Experts
Eisai is sponsoring a symposium featuring three prominent clinical experts in the field of AD, Dr. Alireza Atri, Dr. Sharon Cohen and Dr. Lutz Frölich, who will provide insights on the AD landscape, evolving diagnostic workflow, identifying appropriate patients, and addressing patient needs on Wednesday, March 29. The session aims to provide guidance on the clinical management of patients and drive effective communication between physicians and patients.
AD/PD 2023 Presentations Relating to Eisai’s Key Compounds and Research
Oral Presentations
Poster Presentations
Eisai-Sponsored Symposium
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.
* Protofibrils are large Aβ aggregated soluble species of 75-5000 Kd.1
Media Inquiries:
| Eisai |
|
Eisai Co., Ltd.
Public Relations Department
Eisai Inc. (U.S.)
Libby Holman
Eisai Europe, Ltd.
(Europe, Australia, New Zealand and Russia)
EMEA Communications Department
|
[Notes to editors]
1. About Lecanemab
Lecanemab (brand name in the U.S.: LEQEMBI™) is the result of a strategic research alliance between Eisai and BioArctic. Lecanemab is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). In the U.S., LEQEMBI was granted accelerated approval by the U.S. Food and Drug Administration (FDA) on January 6, 2023. LEQEMBI is indicated for the treatment of Alzheimer’s disease (AD) in the U.S. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved in the U.S. under Accelerated Approval based on reduction in Aβ plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
Prescribing Information.
The Clarity AD study of lecanemab met its primary endpoint and all key secondary endpoints with highly statistically significant results. In the U.S., Eisai submitted a supplemental Biologics License Application (sBLA) to the FDA for approval under the traditional pathway on January 6, 2023. On March 3, 2023, the FDA accepted Eisai’s sBLA based on the Clarity AD clinical data, and the LEQEMBI application has been granted Priority Review, with a Prescription Drug User Fee Act (PDUFA) action date of July 6, 2023. Eisai submitted an application for manufacturing and marketing approval to the Pharmaceuticals and Medical Devices Agency (PMDA) on January 16, 2023, in Japan. The Priority Review was granted by the Ministry of Health, Labour and Welfare (MHLW) on January 26, 2023. Eisai utilized the prior assessment consultation system of PMDA, with the aim of shortening the review period for lecanemab. In Europe, Eisai submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) on January 9, 2023, and accepted on January 26, 2023. In China, Eisai initiated submission of data for a BLA to the National Medical Products Administration (NMPA) of China in December 2022, and the Priority Review was granted on February 27, 2023.
Eisai has completed lecanemab subcutaneous bioavailability study, and subcutaneous dosing is currently being evaluated in the Clarity AD (Study 301) OLE.
Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer’s Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen.
Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing.
2. About the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
3. About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market lecanemab for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody lecanemab back-up was signed in May 2015.
References
1 Söderberg, L., Johannesson, M., Nygren, P. et al. Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease. Neurotherapeutics (2022). https://doi.org/10.1007/s13311-022-01308-6. Accessed February 9, 2023
