Release Details

TOKYO and CAMBRIDGE, Mass., December 12, 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 humanized anti- soluble aggregated amyloid-beta (Aβ) monoclonal antibody “LEQEMBI® Intravenous Infusion” (200 mg, 500mg, lecanemab) will be launched in Japan on December 20, following its scheduled inclusion in the price listing on the Japan National Health Insurance (NHI) Drug Price List.

LEQEMBI received manufacturing and marketing approval for the indication of slowing progression of mild cognitive impairment (MCI) and mild dementia due to Alzheimer’s disease (AD) in Japan on September 25, 2023. In addition to inclusion in Japan’s NHI Drug Price List, the product’s Optimal Clinical Use Guidelines were agreed at a general meeting of the Central Social Insurance Medical Council, an advisory body of the Japanese Ministry of Heath, Labour and Welfare, held today. The launch in Japan marks the second country to have LEQEMBI on the market, following the traditional approval in the United States. In Japan, Eisai and Biogen Japan will co-promote LEQEMBI, with Eisai distributing the product as the Marketing Authorization Holder.

LEQEMBI selectively binds to soluble amyloid-beta (Aβ) aggregates (protofibrils), as well as insoluble Aβ aggregates (fibrils) which are a major component of Aβ plaques, thereby reducing both Aβ protofibrils and Aβ plaques in the brain. LEQEMBI is the first and only approved treatment shown to reduce the rate of disease progression and to slow cognitive and functional decline through this mechanism.

“I am keenly aware of the weight of our responsibility moving forward as we launch LEQEMBI, the world’s first anti-amyloid Alzheimer's disease treatment shown to slow the progress of the disease, in Japan, where Eisai’s value creation has started,” said Haruo Naito, Chief Executive Officer at Eisai. “The establishment of an optimal and fast Alzheimer's disease diagnosis and treatment pathway for patients is a top priority, and close collaboration among the government, dementia specialists, primary care physicians, radiologists, pharmacists, nurses, clinical psychologists, radiology staff, medical office personnel, and caregivers is essential for this purpose. In consideration of the importance of Alzheimer’s disease in Japan, we believe it is imperative that such pathways be established. We are committed to taking this first step towards changing the future of Alzheimer’s disease together with our stakeholders.”

“The availability of LEQEMBI opens a new era in the treatment of Alzheimer’s disease potentially giving patients and their families additional valuable time together and further positions Japan as a leader in caring for an elderly population,” said Christopher A. Viehbacher, President and Chief Executive Officer of Biogen “We will work alongside Eisai to engage the medical community and support the patient journey, especially early diagnosis, as mounting evidence suggests early intervention may provide greater impact on disease progression.”

Eisai will conduct a post-marketing special use results survey in all patients who are administered LEQEMBI (all-case surveillance) until data from a certain number of patients are accumulated, in accordance with an approval condition imposed by the Ministry of Health, Labour and Welfare. In addition, the appropriate use of LEQEMBI will be promoted in accordance with the package insert and the Optimal Clinical Use Guidelines, and training materials will be provided for healthcare professionals to assist with the management and monitoring of amyloid-related imaging abnormalities (ARIA).

Eisai and Biogen are committed to promoting the early detection and diagnosis of AD towards its early treatment, and will do their utmost to deliver LEQEMBI the people with early AD and realize a Dementia-Inclusive Society.

*Protofibrils are large Aβ aggregated soluble species of 75-5000 Kd.^1,2,3.

Notes to Editors

1. Product Outline in Japan

Product name: LEQEMBI® Intravenous Infusion 200mg, LEQEMBI® Intravenous Infusion 500mg
Generic name: Lecanemab (recombinant)Indication for use: Slowing progression of mild cognitive impairment (MCI) and mild dementia due to Alzheimer’s disease.
Dosage and administration: The usual dose of lecanemab (recombinant) is 10mg/kg infused intravenously over approximately 1 hour, once every 2 weeks.
National Health Insurance (NHI) Drug Price (Scheduled to be listed on December 20):
LEQEMBI Intravenous Infusion   200mg              45,777 JPY per vial
LEQEMBI Intravenous Infusion   500mg            114,443 JPY per vial
Packaging:
LEQEMBI Intravenous Infusion   200mg    2mL per vial
LEQEMBI Intravenous Infusion   500mg    5mL per vial

Warnings and Contraindications

1. Warning
   1.1 Prior to initiating administration of this drug, sufficient information should be provided to patients and their families/caregivers about the occurrence rate of ARIA due to this drug, the risk of ARIA, tests necessary for risk management, and measures to be taken when ARIA occurs. This drug should be administered after being informed and obtaining their consent. Also, patients should be in-structed to immediately contact their attending physician if any abnormalities are observed.
   1.2 Prior to initiating administration of this drug, sufficient information should be provided to patients and their families/caregivers about the occurrence rate of ARIA due to this drug, the risk of ARIA, tests necessary for risk management, and measures to be taken when ARIA occurs. This drug should be administered after being informed and obtaining their consent. Also, patients should be in-structed to immediately contact their attending physician if any abnormalities are observed.
2. Contraindications (This drug is contraindicated to the following patients.)
   2.1 Patients with a history of serious hypersensitivity to the ingredients of this drug.
   2.2 Patients with cerebral vasogenic edema confirmed be-fore the start of administration of this drug. [Due to the possible increased risk of ARIA］
   2.3 Patients with 5 or more cerebral microhemorrhages, focal cerebral surface hemosiderosis or cerebral hemorrhage >1 cm in size confirmed before the start of administration of this drug. [Due to the possible increased risk of ARIA］

3. About LEQEMBI

LEQEMBI (lecanemab) is the result of a strategic research alliance between Eisai and BioArctic. LEQEMBI is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). LEQEMBI is an amyloid beta-directed antibody indicated as a disease-modifying treatment for Alzheimer’s disease (AD) in the U.S. The U.S. Food and Drug Administration (FDA) granted traditional approval on July 6, 2023. 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.

Please see full U.S. Prescribing Information for LEQEMBI, including Boxed WARNING.

In Japan, Eisai received approval from the Ministry of Health, Labour and Welfare (MHLW) on September 25, 2023, to manufacture and market lecanemab as a treatment for slowing progression of mild cognitive impairment (MCI) and mild dementia due to AD.

LEQEMBI’s approval was based on Phase 3 data from Eisai’s large, global Clarity AD clinical trial, in which LEQEMBI met its primary endpoint and all key secondary endpoints with statistically significant results and confirmed the clinical benefit of LEQEMBI. The primary endpoint was the global cognitive and functional scale, Clinical Dementia Rating Sum of Boxes (CDR-SB). In the Clarity AD clinical trial, treatment with LEQEMBI reduced clinical decline on CDR-SB by 27% at 18 months compared to placebo. In addition, the secondary endpoint from the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL), which measures information provided by people caring for patients with AD, noted a statistically significant benefit of 37% compared to placebo. The ADCS MCI-ADL assesses the ability of patients to function independently, including being able to dress, feed themselves and participate in community activities. The most common adverse events (>10%) in the LEQEMBI group were infusion reactions, ARIA-H (combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis), ARIA-E (edema/effusion), headache, and fall. Full results of the Clarity AD study were presented at the Clinical Trials on Alzheimer's Disease (CTAD) 2022 conference and simultaneously published in the peer-reviewed medical journal The New England Journal of Medicine(New Window) on November 29, 2022.

Eisai has also submitted applications for approval of lecanemab in 12 countries and regions, including EU and China. In China and Israel, the applications have been designated for priority review, and in Great Britain, lecanemab has been designated for the Innovative Licensing and Access Pathway (ILAP), which aims to reduce the time to market for innovative medicines.

Eisai has completed a lecanemab subcutaneous bioavailability study, and subcutaneous dosing of lecanemab is currently being evaluated in the Clarity AD (Study 301) open-label extension (OLE). A maintenance dosing regimen has been evaluated as part of Study 201.

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 and includes lecanemab as the backbone anti-amyloid therapy.

3. 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 LEQEMBI development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.

4. 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.

5. 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 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 X, LinkedIn and Facebook.

6. 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, two co-developed treatments to address a defining pathology of Alzheimer’s disease, the first treatment to target a genetic form of ALS, the first oral treatment approved for postpartum depression, and the first approved treatment for Friedreich’s ataxia. 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 –Facebook, LinkedIn, X, 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 LEQEMBI; the potential benefits, safety and efficacy of LEQEMBI; 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  LEQEMBI; 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 LEQEMBI; actual timing and content of submissions to and decisions made by the regulatory authorities regarding LEQEMBI; uncertainty of success in the development and potential commercialization of LEQEMBI; 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 a speak only as of the date of this news release. Biogen does not undertake any obligation to publicly update any forward-looking statements.

References

1. https://www.alzforum.org/news/conference-coverage/lecanemab-sweeps-toxic-av-protofibrils-catches-eyes-trialists
2. Sehlin D, Englund H, Simu B, Karlsson M, Ingelsson M, Nikolajeff F, Lannfelt L, Pettersson FE. Large aggregates are the major soluble Aβ species in AD brain fractionated with density gradient ultracentrifugation. PLoS One. 2012;7(2):e32014. https://doi.org/10.1371/journal.pone.0032014 Epub 2012 Feb 15. PMID: 22355408; PMCID: PMC3280222.
3. 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. 2023;20:195-206. https://doi.org/10.1007/s13311-022-01308-6