New Clinical Data Demonstrates Three Years of Continuous Treatment with Dual-Acting LEQEMBI®
(lecanemab-irmb) Continues to Significantly Benefit Early Alzheimer’s Disease Patients Presented at
The Alzheimer’s Association International Conference (AAIC) 2024
- 51% of No Tau / Low Tau Patients Showed Improved Cognition and Function Over Three Years;
Only Lecanemab Has Clinical Data in No Tau / Low Tau Patient Group- Clinical Data and Biomarkers Show Alzheimer’s Disease Does Not Stop Progressing After Plaque
Clearance. Lecanemab’s Dual Action Supports Neuronal Function by Clearing Highly Toxic
Protofibrils that Continue to Cause Neuronal Injury and Death After Rapid Plaque Clearance- Lecanemab Slows Tau Spread Across All Brain Regions

TOKYO and CAMBRIDGE, Mass., July 31, 2024–Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito,“Eisai”) and Biogen Inc. (Nasdaq: BIIB, Headquarters: Cambridge, Massachusetts, CEO: Christopher A.
Viehbacher, “Biogen”) announced today that the latest findings for lecanemab-irmb (U.S. brand name:
LEQEMBI®), an anti-amyloid beta (Aβ) protofibril* antibody for the treatment of early Alzheimer’s disease (AD),were presented at the Alzheimer’s Association International Conference (AAIC) 2024, held in Philadelphia, andvirtually. Dual-acting lecanemab is the only early AD treatment widely available to support neuronal function by
clearing the highly toxic protofibrils that continue to cause neuronal injury and death even after plaques havebeen cleared from the brain. The presentation slides for the two scientific sessions on lecanemab at the AAIC
is available on the Eisai Co. Ltd. Investor Page.
Three Years of Continuous Lecanemab Treatment Reduced Clinical Decline by -0.95 on CDR-SB
Showing Continued Clinically and Personally Meaningful Benefit for Early AD Patients
Clarity AD was a global Phase 3 placebo-controlled, double-blind, parallel-group, randomized study in 1,795
people with early AD (Lecanemab group: 10 mg/kg bi-weekly IV treatment: 898, placebo group: 897). 95% of
patients who completed the core study (18 months) chose to continue in the open-label extension study (OLE).
In the Clarity AD core study, the mean change from baseline between the lecanemab treated group and theplacebo group was -0.45 (P=0.00005) on the primary endpoint of the Clinical Dementia Rating-Sum of Boxes(CDR-SB) global cognitive and functional scale. Over three years of treatment across the core study and OLE,
lecanemab reduced cognitive decline on the CDR-SB by -0.95 compared to the expected decline based on the
Alzheimer’s Disease Neuroimaging Initiative (ADNI)** group.1 A change from 0.5 to 1 on the CDR scoredomains of Memory, Community Affairs and Home/Hobbies is the difference between slight impairment andloss of independence, such as people’s ability to be left alone, remember recent events, participate in daily
activities, complete household chores, function independently and engage in hobbies and intellectualinterests.2,31

Safety Matters.
No new safety findings have been observed with continued lecanemab treatment over three (3) years. Most
Amyloid-related imaging abnormalities (ARIA) occurred in the first six months of treatment. After the first six
months, ARIA rates are low and similar to ARIA rates on placebo. Most patients who had ARIA had CDR-SB
assessments after the event. Sensitivity analyses showed ARIA had no impact on cognition or function. Fromthese results ARIA was not associated with accelerated long-term progression.1 As stated in the FDA productlabel, the incidence and timing of ARIA vary among treatments.4
More than 50% of Patients Who Started Treatment in the Earliest Stage of AD Continued to Show
Improvement After Three Years of Lecanemab Treatment
The Clarity AD study included an optional tau PET substudy and used the tau PET probe MK6240 to identify
patients with no tau or a low accumulation of tau in the brain. As tau begins to accumulate in the brain, cognition
and function start to decline; therefore, patients with no tau or low tau in the brain represent an early stage of
AD. After three years of lecanemab treatment, 59% of these patients (24/41) showed improvement or no decline,
and 51% (21/41) showed improvement from baseline on the CDR-SB. On the ADAS-Cog14 measurement scale,
63% of patients showed improvement or no decline and 61% showed improvement. On the ADCS MCI-ADL,
63% of patients showed improvement or no decline and 59% showed improvement. This suggests that earlier
initiation of treatment with lecanemab may have a significant positive impact on disease progression and may
provide continued benefits to patients with early AD over the long-term.1
Even After Plaque Clearance, AD Continues to Progress When Treatment is Stopped
Study 201 is a multicenter, double-blind, placebo-controlled, Phase 2b trial conducted in 856 patients with early
AD. Appropriate patients participated in the OLE after an off-treatment period of 9-59 months (mean: 24 months)
following the 18-month core study. During the off-treatment period lecanemab’s clinical effect was maintained
but the rate of decline (slope) in patients who stopped therapy reverted back to the rate of decline in patientson placebo as measured by CDR-SB. This indicates that even after Aβ plaque is removed, AD continues toprogress, and reverts to the placebo rate of decline when treatment is stopped.12

After Plaque Removal, Dual-Acting Lecanemab Continues to Positively Impact Biomarkers Over the
Course of Treatment
The key AD fluid biomarkers Aβ42/40, pTau181, pTau217, and glial fibrillary acidic protein (***GFAP) are moresensitive indicators of amyloid and tau development than Amyloid PET and have been shown to re-accumulate
at a faster rate when treatment is discontinued. Modeling data from the Study 201 (Phase 2), Clarity AD (Phase3) and respective OLE studies showed that the half-life of the treatment effect on the fluid biomarkers plasma
Aβ42/40 ratio, pTau181, and GFAP are lost within 0.5 year, 1.6 years and 1.7 years, respectively, while thehalf-life of the treatment effect on amyloid plaque is gradually lost in 12.1 years. When lecanemab treatment
was resumed in the Study 201 OLE after off-treatment period, fluid biomarkers Aβ42/40 ratio, pTau181,
pTau217 and GFAP improved. These results suggest that AD continues to progress when treatment is stopped,even after plaque has been cleared. Patients continue to benefit by remaining on treatment as lecanemab
maintains improvement in the fluid biomarkers of amyloid pathophysiology.1
Lecanemab’s Dual Action on Protofibrils and Plaques Impacts Amyloid and Slows Tau Spread, Offering
Patients a Continuous, Long-Term Treatment for this Chronic and Progressive Disease
Lecanemab is the only widely available early AD treatment that offers a dual mechanism of action designed to
selectively target highly toxic protofibrils in addition to amyloid plaques. Protofibrils accumulate early in the AD
brain and lead to nerve cell function loss, abnormal nerve processes, inflammation, and memory loss. In nonclinical studies, antibodies against protofibrils prevented protofibril-mediated neuronal dysfunction and memory
loss.5 Lecanemab preferentially binds to toxic protofibrils with the highest affinity. After rapidly clearing plaqueand existing protofibrils, lecanemab continuously clears the protofibrils that continue to develop and damage
neurons.1 Protofibrils also play a role in tau spread.5 In the tau PET substudy, continuous lecanemab treatment
slowed the rate of increase in tau accumulation across all brain regions as measured by tau PET.6 CSF MTBRtau243 has high correlation with tau PET and increases with the progression of AD pathology. Treatment withlecanemab slows the increase in CSF MTBR-tau243. Additionally, lecanemab improved pTau217 and otherbiomarkers related to neuroinflammation and neurodegeneration. This indicates a potential disease-modifying
effect on tau pathophysiology.7
3

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 thought to be the most toxic Aβ species that contribute to brain damage in AD and play amajor role in the cognitive decline of this progressive and devastating disease. Protofibrils can cause neuronaldamage in the brain, which can subsequently adversely affect cognitive function through multiple mechanisms.5
The mechanism by which this occurs has been reported not only by increasing the formation of insoluble Aβplaques, 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.8**ADNI is a clinical research project launched in 2005 to develop methods to predict the onset of AD and to
confirm the effectiveness of treatments. The ADNI observational cohort represents the exact population of thosein Clarity AD study; matched ADNI participants show similar degree of decline to placebo group out to 18
months.
*** Glial fibrillar acidic protein (GFAP), a marker of astroglia activation, has been proposed as a biomarker of
Alzheimer’s disease (AD). GFAP expression correlates with Aβ plaque density and cerebrospinal fluid (CSF)
concentration is elevated in symptomatic disease.
MEDIA CONTACTS
Eisai Co., Ltd.
Public Relations Department
TEL: +81 (0)3-3817-5120

Biogen Inc.
Jack Cox+ 1-781-464-3260
public.affairs@biogen.com

Eisai Inc. (U.S.)
Libby Holman+ 1-201-753-1945
Libby_Holman@eisai.com
Eisai Europe, Ltd.
(UK, Europe, Australia, New Zealand and Russia)
EMEA Communications Department+44 (0) 786 601 1272
EMEA-comms@eisai.net
INVESTOR CONTACTS
Eisai Co., Ltd.
Investor Relations Department
TEL: +81 (0) 3-3817-5122

Biogen Inc.
Chuck Triano+ 1-781-464-2442
IR@biogen.com[Notes to editors]
1.

About LEQEMBILEQEMBI (generic name: lecanemab) is the result of a strategic research alliance between Eisai and BioArctic. It is ahumanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) andinsoluble forms of amyloid-beta (Aβ).

4LEQEMBI’s FDA approval was based on Phase 3 data from Eisai’s, global Clarity AD clinical trial, in which it met its
primary endpoint and all key secondary endpoints with statistically significant results.9,10 The primary endpoint was theglobal 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. The mean
CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change frombaseline at 18 months was 1.21 with LEQEMBI and 1.66 with placebo (difference, −0.45; 95% confidence interval [CI],−0.67 to −0.23; P<0.001). 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 forpatients with AD, noted a statistically significant benefit of 37% compared to placebo. The adjusted mean change frombaseline at 18 months in the ADCS-MCI-ADL score was −3.5 in the LEQEMBI group and −5.5 in the placebo group(difference, 2.0; 95% CI, 1.2 to 2.8; P<0.001). 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 mostcommon 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, andfall.
LEQEMBI is approved in the U.S., Japan, China, South Korea, Hong Kong, and Israel for the treatment of MCI due to
AD and mild AD dementia. Eisai has also submitted applications for approval of LEQEMBI in 12 countries and regions.
A supplemental Biologics License Application (sBLA) for intravenous maintenance dosing was submitted to the U.S.
Food and Drug Administration (FDA) in March 2024, which was accepted in June 2024. The rolling submission of a
Biologics License Application (BLA) for maintenance dosing of a subcutaneous injection formulation, which is being
developed to enhance convenience for patients, was initiated in the U.S. under Fast Track status in May 2024.
Since July 2020, the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinicallynormal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as apublic-private partnership between the Alzheimer's Clinical Trial Consortium that provides the infrastructure foracademic 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 antiamyloid therapy.
2.

About the Collaboration between Eisai and Biogen for Alzheimer’s Disease
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 Eisai and Biogen
co-commercializing and co-promoting the product and Eisai having final decision-making authority.

3.

About the Collaboration between Eisai and BioArctic for Alzheimer’s Disease
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercializationof AD treatments. Eisai obtained the global rights to study, develop, manufacture and market lecanemab for thetreatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercializationagreement on the antibody lecanemab 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 thebenefits that health care provides." Under this Concept (also known as human health care (hhc) Concept), we aim toeffectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global

5

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.), us.eisai.com(for U.S. headquarters: Eisai, Inc.) or www.eisai.eu (for Europe, Middle East, Africa, Russia, Australia and New Zealand
headquarters: Eisai Europe Ltd.), and connect with us on X (global and U.S), LinkedIn (for global, U.S. and EMEA) and
Facebook (global).
5.

About Biogen
Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines
to transform patients’ lives and to create value for shareholders and our communities. We apply deep understanding of
human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior
outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth.
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. The website and social media channels are intended foraudiences outside of the UK and Europe.
Biogen Safe Harbor
This news release contains forward-looking statements, 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 andcommercialization 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 resultsfrom later stage or larger scale clinical studies and do not ensure regulatory approval. You should not place undue
reliance on these statements.
These statements involve risks and uncertainties that could cause actual results to differ materially from those reflectedin such statements, including without limitation unexpected concerns that may arise from additional data, analysis or
results obtained during clinical studies; the occurrence of adverse safety events; risks of unexpected costs or delays; therisk 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 potentialcommercialization 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; and third party
collaboration risks, results of operations and financial condition. The foregoing sets forth many, but not all, of the factorsthat could cause actual results to differ from Biogen's expectations in any forward-looking statement. Investors should

6consider this cautionary statement as well as the risk factors identified in Biogen's most recent annual or quarterly reportand in other reports Biogen has filed with the U.S. Securities and Exchange Commission. These statements speak only
as of the date of this news release. Biogen does not undertake any obligation to publicly update any forward-looking
statements.
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Sperling, R., Selkoe, D., Reyderman, L., Youfang, C., Van Dyck, C. (2024, July 28 - August 1). Does the Current
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Alzheimer's Association International Conference, Philadelphia, PA, United States.

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Cohen S., et al. J Prev Alzheimers Dis.2022;9(3):507-522.

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Willis, B., Charil, A., Fox, N., Teunissen, C. (2024, July 28-August 1). Beyond Amyloid Removal with Lecanemab
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Wildsmith, K., Pallavi, S., Horie, K., Reyderman, K., Charil, A., Kanekivo, M., Yin, H., Li, D., Koyama, A., Dhadda, S.
Irizarry, M., Kramer, L. (2024, July 28-August 1). Lecanemab Slows Amyloid-Induced Tau Pathology as Supported by
CSF MTBR-tau243 in Clarity AD. [Developing Topic] Alzheimer’s Association International Conference, Philadelphia,
PA, United States

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Ono K, Tsuji M. Protofibrils of Amyloid-β are Important Targets of a Disease-Modifying Approach for Alzheimer's
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Trials on Alzheimer's Disease (CTAD) conference. Available at:https://www.eisai.co.jp/news/2022/news202285.html

10. van Dyck. C, et al. Lecanemab in Early Alzheimer's Disease. The New England Journal of Medicine. DOI:
10.1056/NEJMoa2212948. https://www.nejm.org/doi/full/10.1056/NEJMoa2212948.

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