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 the humanized amyloid-beta (Aβ) monoclonal antibody “Leqembi?” (brand name, generic name: lecanemab) has been granted a Marketing Authorization by the Medicines and Healthcare products Regulatory Agency (MHRA) in Great Britain. Lecanemab is indicated for the treatment of mild cognitive impairment (MCI) and mild dementia due to Alzheimer’s disease (AD) in adult patients that are apolipoprotein E ε4 (ApoE ε4)* heterozygotes or non-carriers.1 Lecanemab becomes the first treatment for early AD (MCI and mild dementia due to AD) that targets an underlying cause of the disease, to be authorized in a country in Europe.

Lecanemab selectively binds to Aβ aggregate species, with preferential activity for toxic Aβ protofibrils**
(as well as fibrils, which are a major component of Aβ plaques). It binds to these aggregate Aβ
species to neutralize and clear them from the brain.

The approval was primarily based on Phase 3 data from Eisai’s global, placebo-controlled, double-blind,
parallel-group, randomized Clarity AD clinical trial, in which the medicine met its primary endpoint
(change from baseline in the Clinical Dementia Rating Sum of Boxes [CDR-SB]? at 18 months) and all
key secondary endpoints with statistically significant results. In the indicated population in Great Britain,
the most common adverse reactions were infusion-related reaction, amyloid-related imaging
abnormalities with hemorrhage (small spots of bleeding) (ARIA-H)?, fall, headache and amyloid-related
imaging abnormalities with cerebral edema (build-up of fluid) (ARIA-E)??.

In the United Kingdom, it is estimated that 982,000 people are living with dementia, and AD is the
cause in 60-70% of people with dementia. These numbers are expected to rise, as the population
ages.

Eisai is working collaboratively with the National Institute for Health and Care Excellence (NICE), the
Scottish Medicines Consortium (SMC) and the National Health Service (NHS) to make this medicine
available to eligible people living with early AD as soon as possible.

Eisai serves as the lead for lecanemab’s development and regulatory submissions globally with Eisai
and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making
authority. In Great Britain, Eisai and Biogen will co-promote the medicine, with Eisai distributing the
product as the Marketing Authorization holder.

*Apolipoprotein E is a protein involved in the metabolism of fats in humans. It is implicated in AD.

**Protofibrils are thought to be the most toxic Aβ species that contribute to brain damage in AD and play a major role in the cognitive decline of this progressive and devastating disease. Protofibrils can cause neuronal damage in the brain, which can subsequently adversely affect cognitive function through multiple mechanisms.? The mechanism by which this occurs has been reported not only by increasing the formation of insoluble Aβ plaques, but also by directly damaging signaling between neurons and other cells. It is believed that reducing protofibrils may reduce neuronal damage and cognitive impairment, potentially preventing the progression of AD.

?CDR-SB is a commonly used diagnostic tool, which can help to stage dementia due to AD. It is a global cognitive and functional scale that measures six domains of functioning, including memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care.

?ARIA-H: amyloid-related imaging abnormalities with hemorrhage (microhemorrhages, and superficial siderosis).

??ARIA-E: amyloid-related imaging abnormalities with oedema (edema/effusion).

LEQEMBI selectively binds to soluble 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 approved treatment shown to reduce the rate of disease progression and to slow cognitive and functional decline through this mechanism. LEQEMBI is also approved in the U.S., Japan, China, South Korea, Hong Kong, and Israel, and is being marketed in the U.S., Japan, and China.

LEQEMBI’s approval is based on the large global Phase 3 Clarity AD study. In the Clarity AD study, LEQEMBI met its primary endpoint and all key secondary endpoints with statistically significant results. ^1,2 In the UAE, it is reported that 4.09% of those over 60 years old have dementia. ³ AD is considered the most common cause of dementia, typically accounting for 60-70% of cases.⁴

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. Biogen will commercialize LEQEMBI in the UAE.

* Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to be the most toxic form of Aβ, having a primary role in the cognitive decline associated with this progressive, debilitating condition. ⁵ Protofibrils cause injury to neurons in the brain, which in turn, can negatively impact cognitive function via multiple mechanisms, not only increasing the development of insoluble Aβ plaques but also increasing direct damage to brain cell membranes and the connections that transmit signals between nerve cells or nerve cells and other cells. It is believed the reduction of protofibrils may prevent the progression of AD by reducing damage to neurons in the brain and cognitive dysfunction. ⁶

References

1. Eisai presents full results of lecanemab Phase 3 confirmatory Clarity AD study for early Alzheimer’s disease at Clinical Trials on Alzheimer’s Disease (CTAD) conference. Available at: https://www.eisai.co.jp/news/2022/news202285.html
2. van Dyck, H., et al. Lecanemab in Early Alzheimer’s Disease. New England Journal of Medicine. 2023;388:9-21. https://www.nejm.org/doi/full/10.1056/NEJMoa2212948.
3. Qassem T., et al, Prevalence and economic burden of dementia in the Arab world. BJPsych Open. 2023 Jul; 9(4): e126. https://doi.org/10.1192%2Fbjo.2023.517
4. World Health Organization. Dementia Fact Sheet. March 2023. Available at: https://www.who.int/news-room/fact-sheets/detail/dementia.
5. Amin L, Harris DA. Aβ receptors specifically recognize molecular features displayed by fibril ends and neurotoxic oligomers. Nat Commun. 2021;12:3451. doi:10.1038/s41467-021-23507-z
6. Ono K, Tsuji M. Protofibrils of Amyloid-β are Important Targets of a Disease-Modifying Approach for Alzheimer’s Disease. Int J Mol Sci. 2020;21(3):952. doi: 10.3390/ijms21030952. PMID: 32023927; PMCID: PMC7037706.

The SC formulation (including initiation and maintenance dosing) received Fast Track designation from the
U.S. Food and Drug Administration (FDA). In agreement with the FDA, Eisai initiated a rolling submission
and review for SC maintenance dosing in May 2024. In parallel, discussions are ongoing with the FDA
regarding optimal dosage and the fastest regulatory pathway for the SC initiation dosing. There are no
changes to the previously announced timeline for the SC application at this time. We expect to complete
the rolling application for SC maintenance dosing in the third quarter of fiscal year 2024 ending March
2025, with a review period of six months if designated for priority review or ten months under standard
review. For SC initiation dosing, we aim to obtain a regulatory approval by the end of fiscal year 2025
ending March 2026.

A supplemental Biologics License Application (sBLA) for intravenous (IV) maintenance dosing was
submitted to the FDA in March 2024 and accepted in June of the same year. The PDUFA (Prescription
Drugs User Fee Act) action date is set for January 25, 2025.

Eisai is committed to making the IV maintenance dosing and SC formulation available as new treatment
options to people with early AD as soon as possible.

Eisai serves as the lead for lecanemab’s development and regulatory submissions globally with both Eisai
and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making
authority.

Ravuconazole, the active ingredient of fosravuconazole, is an antifungal agent discovered and developed
by Eisai. Fosravuconazole is a prodrug of ravuconazole, which improves its solubility and bioavailability.
In Japan, Seren Pharma (Headquarters: Tokyo) and Sato Pharma have developed fosravuconazole based
on the exclusive rights to develop, commercialize, and sublicense granted by Eisai. The treatment has
been marketed by Sato Pharma as the oral antifungal agent Nailin? for the indication of “onychomycosis”
since July 2018, which Eisai is co-promoting.

Under the terms of the agreement, Eisai will receive a contractual upfront payment, and the rights to receive
regulatory milestone payments and royalties based on sales over a certain period. Eisai will retain
development and commercialization rights related to mycetoma, a neglected tropical disease, and its
associated conditions, as these are excluded from the licensing.

Upon the conclusion of this agreement, Eisai hopes to maximize the value of fosravuconazole in the
Asia/Oceania region, ensuring the earliest possible contribution to patients in need of the medicine.

*10 ASEAN nations, Australia, New Zealand, South Korea, and Taiwan

LEQEMBI selectively binds to soluble Aβ aggregates (protofibrils*), as well as insoluble Aβ aggregates
(fibrils) which are a major component of Aβ plaques in AD, 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. South Korea
is the fourth country to grant approval, following approvals in the U.S., Japan, and China.

It is estimated there were approximately 900,000 dementia patients in South Korea in 2021,1 with one
in ten people over the age of 65 suffering from dementia, and one in five from mild cognitive impairment
(MCI). The average annual nursing care and medical costs per dementia patient is estimated to be
21.1 million KRW, while the cost for patients with severe dementia reaches 33.1 million KRW.

Eisai serves as the lead of LEQEMBI development and regulatory submissions globally with both Eisai
and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making
authority. In South Korea, Eisai Korea Inc. will distribute the product and conduct information provision
activities. Eisai is committed to working together with healthcare professionals and other stakeholders
to realize the early diagnosis and treatment of AD.

* Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to be
the most toxic form of Aβ, having a primary role in the cognitive decline associated with this
progressive, debilitating condition. Protofibrils cause injury to neurons in the brain, which in turn, can
negatively impact cognitive function via multiple mechanisms, not only increasing the development
of insoluble Aβ plaques but also increasing direct damage to brain cell membranes and the
connections that transmit signals between nerve cells or nerve cells and other cells. It is believed the
reduction of protofibrils may prevent the progression of AD by reducing damage to neurons in the
brain and cognitive dysfunction.

The BLA is based on data from the Clarity AD (Study 301) open-label extension (OLE) and modeling
of observed data. If approved by the FDA, the LEQEMBI autoinjector could be used to administer
LEQEMBI at home or at medical facilities. The injection process requires less time than the IV
formulation. As part of the subcutaneous autoinjector 360 mg weekly maintenance regimen under
review, patients who have completed the biweekly IV initiation phase would receive weekly doses that
maintain effective drug concentrations to sustain the clearance of highly toxic protofibrils* which can
continue to cause neuronal injury even after the amyloid-beta (Aβ) plaque has been cleared from the
brain.

AD is an ongoing neurotoxic process that begins before and continues after plaque deposition. Data
suggest that early and continuing treatment may prolong the benefit even after plaque is cleared from
the brain. This SC autoinjector is easier for patients and their care partners to use, and may reduce the
need for hospital visits and nursing care compared to intravenous (IV) administration. In addition to
potentially maintaining the clinical and biomarker benefits, subcutaneous maintenance dosing may be
more convenient for patients and their care partners to continue the treatment.

LEQEMBI is now approved in the U.S., Japan and China, and applications have been submitted for
review in the European Union, Australia, Brazil, Canada, Hong Kong, Great Britain, India, Israel, Russia,
Saudi Arabia, South Korea, Taiwan, Singapore and Switzerland. Eisai submitted to the FDA a
Supplemental Biologics License Application (sBLA) for monthly LEQEMBI intravenous (IV)
maintenance dosing in March 2024.

Eisai serves as the lead for lecanemab’s development and regulatory submissions globally with both
companies co-commercializing and co-promoting the product and Eisai having final decision-making
authority.

* Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to be
the most toxic form of Aβ, having a primary role in the cognitive decline associated with this progressive,
debilitating condition. Protofibrils cause injury to neurons in the brain, which in turn, can negatively
impact cognitive function via multiple mechanisms, not only increasing the development of insoluble Aβ
plaques but also increasing direct damage to brain cell membranes and the connections that transmit
signals between nerve cells or nerve cells and other cells. It is believed the reduction of protofibrils may
prevent the progression of AD by reducing damage to neurons in the brain and cognitive dysfunction.

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that the injection formulation of its in-house discovered antiepileptic drug (AED) Fycompa? (perampanel hydrate) for intravenous (IV) infusion has been launched in Japan. The injection formulation of Fycompa received manufacturing and marketing approval on January 18, 2024 and was included in the Japan’s National Health Insurance (NHI) Drug Price List today.

Fycompa is a first-in-class AED discovered at Eisai’s Tsukuba Research Laboratories. The agent is a 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 of seizures 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 via routes other than oral administration.

Since Fycompa is the only AMPA receptor antagonist-based AED, Eisai developed this injection formulation to meet the needs of patients who are unable to use oral administration, and leading to the launch today.

Eisai considers neurology, including epilepsy, a therapeutic area of focus. As a human health care company, Eisai pursues its mission to provide “seizure freedom” to a greater number of patients with epilepsy. Eisai remains committed to further addressing the diverse needs of, and increasing the benefits provided to, patients with epilepsy and their families.

Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120

The PSJ Award for Drug Research and Development is one of a series of awards presented by the PSJ and is dedicated to researchers who have conducted outstanding research work that has contributed to medicine through the innovative development of a pharmaceutical drug or applicable technology related to the pharmaceutical sciences. Award recipients are evaluated by the PSJ based on the ingenuity of the research itself as well as the effectiveness and safety of the related pharmaceutical product(s) or the innovativeness of the related medical treatment or treatment technology. Eisai was a four-time winner of the award for drug discovery research: in 1998 on donepezil hydrochloride, an Alzheimer’s disease treatment; in 2013 on eribulin mesylate, an anti-cancer agent; in 2020 on lenvatinib, a multikinase inhibitor; and in 2021 on perampanel, an AMPA-type glutamate receptor antagonist.

PSJ shared the following rationale for selecting lemborexant: “Unlike conventional drugs, based on the fact that the main cause of insomnia is the nocturnal hyperactivation of the wakefulness pathway, the compound targets inhibition of the wakefulness system, which is considered a rational therapeutic approach. The compound is highly original in its unique structure based on trisubstituted cyclopropanes, and has overcome many challenges in its optimization to a compound with a balanced profile by overcoming many pharmacokinetic and safety issues. In preclinical and clinical studies, it has demonstrated a superior efficacy and safety profile that sets it apart from conventional drugs, and the compound is meeting the unmet medical needs of many insomnia patients both in Japan and overseas.”

Lemborexant is currently approved for the indication of insomnia in over 15 countries, including Japan, the U.S., Canada, Australia, and countries in Asia.

Eisai considers neurology, including insomnia, a therapeutic area of focus. Eisai strives to create innovative products in therapeutic areas with high unmet medical needs as soon as possible, and will further contribute to addressing the diverse needs of, as well as increasing the benefits provided to, those living with the disease and their families.

Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120

This application is based on the results of JETALS (The Japan Early-Stage Trial of Ultrahigh-Dose Methylcobalamin for ALS), a Phase III trial to evaluate efficacy and safety of ultrahigh-dose methylcobalamin (mecobalamin) in early onset ALS patients, that was conducted as an investigator-initiated trial by a research team with Extraordinary Professor Ryuji Kaji (Principal Investigator), Tokushima University, and Professor Yuishin Izumi (Coordinating Investigator), the Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, and Professor Satoshi Kuwabara (Coordinating Investigator), the Department of Neurology, Chiba University Graduate School of Medicine. The results of JETALS were published in the peer-reviewed journal JAMA Neurology.

ALS is an intractable, progressive, neurodegenerative disease that results in severe muscle atrophy and weakness in the muscles due to motor neuron dysfunction. As the main cause of death is respiratory failure due to paralysis of the respiratory muscles, without the use of an artificial respirator, death occurs within approximately 3 to 6 years from the onset of the disease. The number of patients in Japan is estimated to be approximately 10,000. Currently, there is no curative treatment established for ALS, and since there are only limited number of medicines approved in Japan and abroad, this is a disease with significant unmet medical needs.

Eisai considers neurology a therapeutic area of focus. As a human healthcare company, Eisai is committed to fulfill unmet medical needs in neurology and further its contribution to improving the benefit of patients and the people in the daily living domain.

Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has been listed in the 2024 Global 100 Most Sustainable Corporations in the World (Global 100), a global ranking by Canada-based media and investment advisory company, Corporate Knights, Inc. This marks Eisai’s eighth inclusion on the list. Ranked 35th, Eisai is the highest ranking company among global pharmaceutical companies. Also, Eisai became the highest ranking Japanese company among the three Japanese companies listed in the Global 100 (please visit?here?for the Global 100 ranking).

The Global 100 evaluates the sustainability of more than 6,700 of the world’s major corporations based on various corporate initiatives in areas such as ESG (environment, society and governance). Since 2005, those companies ranking among the top 100 in the world have been announced each year. The Global 100 is based on up to 25 key performance indicators covering ESG initiatives, with the evaluations carried out based on data publicly disclosed in financial filings, integrated reports, or through other such channels. Eisai was highly evaluated, particularly in indicators for reducing greenhouse gas emissions, and enhancing employee value such as safe work environment, sick leave support system and employee retention rate.

Eisai’s corporate concept is to give first thought to patients and the people in the daily living domain, and increase the benefits that health care provides to them as well as meet their diversified healthcare needs worldwide. Based on this human health care?(hhc) corporate concept, Eisai is striving to sustainably enhance corporate value by strengthening its ESG initiatives and increasing non-financial value.

Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120