TOKYO and CAMBRIDGE, Mass., May 15, 2024 – Eisai Co., Ltd. (Headquarters: Tokyo, CEO: HaruoNaito, “Eisai”) and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts,CEO: Christopher A. Viehbacher, “Biogen”) announced today that Eisai has initiated the rollingsubmission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA)for lecanemab-irmb (U.S. brand name: LEQEMBI®) subcutaneous autoinjector for weekly maintenancedosing after it was granted Fast Track designation by the FDA. LEQEMBI is indicated for the treatmentof Alzheimer’s disease (AD) in patients with Mild Cognitive Impairment (MCI) or mild dementia stage ofdisease (collectively referred to as early AD).
The BLA is based on data from the Clarity AD (Study 301) open-label extension (OLE) and modelingof observed data. If approved by the FDA, the LEQEMBI autoinjector could be used to administerLEQEMBI at home or at medical facilities. The injection process requires less time than the IVformulation. As part of the subcutaneous autoinjector 360 mg weekly maintenance regimen underreview, patients who have completed the biweekly IV initiation phase would receive weekly doses thatmaintain effective drug concentrations to sustain the clearance of highly toxic protofibrils* which cancontinue to cause neuronal injury even after the amyloid-beta (Aβ) plaque has been cleared from thebrain.
AD is an ongoing neurotoxic process that begins before and continues after plaque deposition. Datasuggest that early and continuing treatment may prolong the benefit even after plaque is cleared fromthe brain. This SC autoinjector is easier for patients and their care partners to use, and may reduce theneed for hospital visits and nursing care compared to intravenous (IV) administration. In addition topotentially maintaining the clinical and biomarker benefits, subcutaneous maintenance dosing may bemore 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 forreview 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 aSupplemental 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 bothcompanies co-commercializing and co-promoting the product and Eisai having final decision-makingauthority.
* Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to bethe most toxic form of Aβ, having a primary role in the cognitive decline associated with this progressive,debilitating condition.1 Protofibrils cause injury to neurons in the brain, which in turn, can negativelyimpact cognitive function via multiple mechanisms, not only increasing the development of insoluble Aβplaques but also increasing direct damage to brain cell membranes and the connections that transmitsignals between nerve cells or nerve cells and other cells. It is believed the reduction of protofibrils mayprevent the progression of AD by reducing damage to neurons in the brain and cognitive dysfunction.2
About lecanemab (LEQEMBI®)
Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. It is ahumanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregatedsoluble (protofibril) and insoluble forms of amyloid-beta (Aβ).3 Lecanemab is approved in the U.S.,4Japan,5 and China.6. In the U.S., Japan and China, the indications are as follows;
• U.S.: For the treatment of Alzheimer’s disease (AD). It should be initiated in patients withMCI or mild dementia stage of disease.3,7
• Japan: For slowing progression of MCI and mild dementia due to AD.5
• China: For the treatment of MCI due to AD and mild AD dementia.
6LEQEMBI’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 significantresults.3 The primary endpoint was the global cognitive and functional scale, Clinical DementiaRating Sum of Boxes (CDR-SB). In the Clarity AD clinical trial, treatment with lecanemab reducedclinical decline on CDR-SB by 27% at 18 months compared to placebo.3 The mean CDR-SB scoreat baseline was approximately 3.2 in both groups. The adjusted least-squares mean change frombaseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, −0.45; 95%confidence interval [CI], −0.67 to −0.23; P<0.001).3In addition, the secondary endpoint from theAD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCIADL), which measures information provided by people caring for patients with AD, noted astatistically significant benefit of 37% compared to placebo.3 The adjusted mean change frombaseline at 18 months in the ADCS-MCI-ADL score was −3.5 in the lecanemab group and −5.5 inthe placebo group (difference, 2.0; 95% CI, 1.2 to 2.8; P<0.001).3 The ADCS MCI-ADL assessesthe ability of patients to function independently, including being able to dress, feed themselves andparticipate in community activities. The most common adverse events (>10%) in the lecanemabgroup were infusion reactions, ARIA-H (combined cerebral microhemorrhages, cerebralmacrohemorrhages, and superficial siderosis), ARIA-E (edema/effusion), headache, and fall.3
Eisai has also submitted applications for approval of lecanemab in 14 countries and regions,including the European Union (EU).
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 theirbrains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between theAlzheimer's Clinical Trial Consortium that provides the infrastructure for academic clinical trials inAD and related dementias in the U.S, funded by the National Institute on Aging, part of the NationalInstitutes of Health, Eisai and Biogen. Since January 2022, the Tau NexGen clinical study forDominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer NetworkTrials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing andincludes lecanemab as the backbone anti-amyloid therapy.
About the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint development and commercialization of ADtreatments since 2014. Eisai serves as the lead of lecanemab development and regulatorysubmissions globally with both companies co-commercializing and co-promoting the product andEisai 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 humanhealth care (hhc) Concept), we aim to effectively achieve social good in the form of relieving anxietyover health and reducing health disparities. With a global network of R&D facilities, manufacturingsites and marketing subsidiaries, we strive to create and deliver innovative products to targetdiseases with high unmet medical needs, with a particular focus in our strategic areas of Neurologyand 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), byworking 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.For audiences based in the UK and Europe,please visit www.eisai.eu and Eisai EMEA LinkedIn.
About Biogen
Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science todeliver new medicines to transform patients’ lives and to create value for shareholders and ourcommunities. We apply deep understanding of human biology and leverage different modalities toadvance first-in-class treatments or therapies that deliver superior outcomes. Our approach is totake 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 websiteat www.biogen.com. Follow Biogen on social media – Facebook, LinkedIn, X, YouTube.
References
1. Amin L, Harris DA. Aβ receptors specifically recognize molecular features displayed by fibrilends and neurotoxic oligomers. Nat Commun. 2021;12:3451. doi:10.1038/s41467-021-23507-z
2. Ono K, Tsuji M. Protofibrils of Amyloid-β are Important Targets of a Disease-ModifyingApproach for Alzheimer's Disease. Int J Mol Sci. 2020;21(3):952. doi: 10.3390/ijms21030952.PMID: 32023927; PMCID: PMC7037706.
3. LEQEMBI. Prescribing information. Eisai Inc. 2023.
4. US Food and Drug Administration. FDA Grants Accelerated Approval for Alzheimer’s DiseaseTreatment. Available at: https://www.fda.gov/news-events/press-announcements/fda-grantsaccelerated-approval-alzheimers-disease-treatment. Last accessed: March 2024.
5. Eisai Global. 2023. “LEQEMBI® Intravenous Infusion” (Lecanemab) Approved for theTreatment of Alzheimer’s Disease in Japan Available at:https://www.eisai.com/news/2023/news202359.html. Last accessed: March 2024.
6. Eisai Global. 2024. “LEQEMBI®” (Lecanemab) Approved for the Treatment of Alzheimer’sDisease in China. Available at: https://www.eisai.com/news/2024/news202403.html. Lastaccessed: March 2024.
7. van Dyck, H., et al. Lecanemab in Early Alzheimer’s Disease. New England J