LEQEMBI® (lecanemab-irmb) NAMED ONE OF TIME's BEST INVENTIONS OF 2023

Recognized in the Medical Care Category

NUTLEY, N.J., and CAMBRIDGE, Mass., Oct. 24, 2023 /PRNewswire/ -- Eisai Inc. and Biogen Inc. are honored to announce today that TIME has selected LEQEMBI® (lecanemab-irmb) as one of the Best Inventions of 2023 in the Medical Care category.

LEQEMBI is the first and only approved treatment for patients with mild cognitive impairment or mild dementia stage of Alzheimer's disease (AD). AD is a type of dementia that affects memory and thinking skills as well as behavior impacting a person's ability to perform daily activities. It is a chronic neurodegenerative disorder that is both progressive and irreversible, affecting millions in the U.S. ^1,2

TIME's annual list of the Best Inventions features "200 extraordinary innovations changing lives." To compile the list, TIME solicited nominations from its editors and correspondents around the world, and through an open online application process, paying special attention to growing fields such as AI, green energy, and sustainability. TIME then evaluated each contender on a number of key factors, including originality, efficacy, ambition, and impact.

INDICATION

LEQEMBI is indicated for the treatment of Alzheimer's disease. 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. 

WARNING: AMYLOID RELATED IMAGING ABNORMALITIES (ARIA)

• Monoclonal antibodies directed against aggregated forms of amyloid beta, including LEQEMBI, can cause amyloid related imaging abnormalities (ARIA), characterized as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). Incidence and timing of ARIA vary among treatments. ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events rarely can occur. Serious intracerebral hemorrhages >1 cm, some of which have been fatal, have been observed in patients treated with this class of medications.
  • Apolipoprotein E ε4 (ApoE ε4) Homozygotes: Patients who are ApoE ε4 homozygotes (approximately 15% of Alzheimer's disease patients) treated with this class of medications, including LEQEMBI, have a higher incidence of ARIA, including symptomatic, serious, and severe radiographic ARIA, compared to heterozygotes and noncarriers. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to testing, prescribers should discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results. Prescribers should inform patients that if genotype testing is not performed, they can still be treated with LEQEMBI; however, it cannot be determined if they are ApoE ε4 homozygotes and at higher risk for ARIA.
• Consider the benefit of LEQEMBI for the treatment of Alzheimer's disease and potential risk of serious adverse events associated with ARIA when deciding to initiate treatment with LEQEMBI

<sup>1. Alzheimer's Association. 2022 Alzheimer's Disease Facts and Figures. Alzheimers Dement 2022;18. Retrieved July 19, 2022, from https://www.alz.org/media/documents/alzheimers-facts-and-figures.pdf
2. Terracciano A. Sutin AR. Personality and Alzheimer's disease: An integrative review. Personal Disord. 2019 Jan 10(1):4-12;. Doi:10.1037/per0000268. PMID:30604979; PMCID: PMC6345278.</sup>

CONTRAINDICATION

LEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients of LEQEMBI. Reactions have included angioedema and anaphylaxis.

WARNINGS AND PRECAUTIONS

Amyloid Related Imaging Abnormalities

• LEQEMBI can cause ARIA-E and ARIA-H. ARIA-E can be observed on MRI as brain edema or sulcal effusions, and ARIA-H as microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with Alzheimer's disease. ARIA-H associated with monoclonal antibodies directed against aggregated forms of beta amyloid generally occurs in association with an occurrence of ARIA-E. ARIA-H and ARIA-E can occur together. ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, rarely can occur. Reported symptoms associated with ARIA may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms associated with ARIA usually resolve over time.

ARIA Monitoring and Dose Management Guidelines

• Obtain recent baseline brain magnetic resonance imaging (MRI) prior to initiating treatment with LEQEMBI. Obtain an MRI prior to the 5th, 7th and 14th infusions.
• Recommendations for dosing in patients with ARIA-E and ARIA-H depend on clinical symptoms and radiographic severity. Depending on ARIA severity, use clinical judgment in considering whether to continue dosing, temporarily discontinue treatment, or permanently discontinue LEQEMBI.
• Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI if indicated. If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment.
• There is no experience in patients who continued dosing through symptomatic ARIA-E or through asymptomatic, but radiographically severe, ARIA-E. There is limited experience in patients who continued dosing through asymptomatic but radiographically mild to moderate ARIA-E. There are limited data in dosing patients who experienced recurrent ARIA-E.

 Incidence of ARIA 

• In Study 2, symptomatic ARIA occurred in 3% (29/898) of LEQEMBI-treated patients. Serious symptoms associated with ARIA were reported in 0.7% (6/898) of patients treated with LEQEMBI.  Clinical symptoms associated with ARIA resolved in 79% (23/29) of patients during the period of observation.
• Including asymptomatic radiographic events, ARIA was observed in LEQEMBI: 21% (191/898); placebo: 9% (84/897). ARIA-E was observed in LEQEMBI: 13% (113/898); placebo: 2% (15/897). ARIA-H was observed in LEQEMBI: 17% (152/898); placebo: 9% (80/897). There was no increase in isolated ARIA-H for LEQEMBI vs placebo.

ApoE ε4 Carrier Status and Risk of ARIA

• In Study 2, 16% (141/898) of patients in the LEQEMBI arm were ApoE ε4 homozygotes, 53% (479/898) were heterozygotes, and 31% (278/898) were noncarriers.
• The incidence of ARIA was higher in ApoE ε4 homozygotes (LEQEMBI: 45%; placebo: 22%) than in heterozygotes (LEQEMBI: 19%; placebo: 9%) and noncarriers (LEQEMBI: 13%; placebo: 4%). Among patients treated with LEQEMBI, symptomatic ARIA-E occurred in 9% of ApoE ε4 homozygotes compared with 2% of heterozygotes and 1% noncarriers. Serious events of ARIA occurred in 3% of ApoE ε4 homozygotes, and approximately 1% of heterozygotes and noncarriers.   
• The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers.

Radiographic Findings

• The majority of ARIA-E radiographic events occurred early in treatment (within the first 7 doses), although ARIA can occur at any time and patients can have more than 1 episode. The maximum radiographic severity of ARIA-E in patients treated with LEQEMBI was mild in 4% (37/898), moderate in 7% (66/898), and severe in 1% (9/898). Resolution on MRI occurred in 52% of ARIA-E patients by 12 weeks, 81% by 17 weeks, and 100% overall after detection.  The maximum radiographic severity of ARIA-H microhemorrhage in LEQEMBI-treated patients was mild in 9% (79/898), moderate in 2% (19/898), and severe in 3% (28/898) of patients; superficial siderosis was mild in 4% (38/898), moderate in 1% (8/898) , and severe in 0.4% (4/898). Among LEQEMBI-treated patients, the rate of severe radiographic ARIA-E was highest in ApoE ε4 homozygotes 5% (7/141), compared to heterozygotes 0.4% (2/479) or noncarriers 0% (0/278). Among LEQEMBI-treated patients, the rate of severe radiographic ARIA-H was highest in ApoE ε4 homozygotes 13.5% (19/141), compared to heterozygotes 2.1% (10/479) or noncarriers 1.1% (3/278).

Intracerebral Hemorrhage

• Intracerebral hemorrhage >1 cm in diameter was reported in 0.7% (6/898) of patients in Study 2 after treatment with LEQEMBI compared to 0.1% (1/897) on placebo. Fatal events of intracerebral hemorrhage in patients taking LEQEMBI have been reported.

Concomitant Antithrombotic Medication:

• In Study 2, baseline use of antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) was allowed if the patient was on a stable dose. The majority of exposures to antithrombotic medications were to aspirin. Antithrombotic medications did not increase the risk of ARIA with LEQEMBI. The incidence of intracerebral hemorrhage was 0.9% (3/328 patients) in patients taking LEQEMBI with a concomitant antithrombotic medication at the time of the event compared to 0.6% (3/545 patients) in those who did not receive an antithrombotic. Patients taking LEQEMBI with an anticoagulant alone or combined with an antiplatelet medication or aspirin had an incidence of intracerebral hemorrhage of 2.5% (2/79 patients) compared to none in patients who received placebo.
• Because intracerebral hemorrhages >1 cm in diameter have been observed in patients taking LEQEMBI, additional caution should be exercised when considering the administration of anticoagulants or a thrombolytic agent (e.g., tissue plasminogen activator) to a patient already being treated with LEQEMBI.

Other Risk Factors for Intracerebral Hemorrhage:

• Patients were excluded from enrollment in Study 2 for findings on neuroimaging that indicated an increased risk for intracerebral hemorrhage. These included findings suggestive of cerebral amyloid angiopathy (prior cerebral hemorrhage >1 cm in greatest diameter, >4 microhemorrhages, superficial siderosis, vasogenic edema) or other lesions (aneurysm, vascular malformation) that could potentially increase the risk of intracerebral hemorrhage. The presence of an ApoE ε4 allele is also associated with cerebral amyloid angiopathy, which has an increased risk for intracerebral hemorrhage. Caution should be exercised when considering the use of LEQEMBI in patients with factors that indicate an increased risk for intracerebral hemorrhage and in particular for patients who need to be on anticoagulant therapy.

Hypersensitivity Reactions
Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred in LEQEMBI-treated patients. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction, and initiate appropriate therapy. 

Infusion-Related Reactions

• In Study 2, infusion-related reactions were observed in LEQEMBI: 26% (237/898); placebo: 7% (66/897), and the majority of cases in LEQEMBI-treated patients (75%, 178/237) occurred with the first infusion. Infusion-related reactions were mostly mild (69%) or moderate (28%) in severity. Infusion-related reactions resulted in discontinuations in 1% (12/898) of LEQEMBI-treated patients. Symptoms of infusion-related reactions included fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation.
• In the event of an infusion-related reaction, the infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Prophylactic treatment with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids prior to future infusions may be considered. 

 ADVERSE REACTIONS

• In Study 2, the most common adverse reactions leading to discontinuation of LEQEMBI was ARIA-H microhemorrhages that led to discontinuation in 2% (15/898) of patients treated with LEQEMBI compared to <1% (1/897) of patients on placebo.
• In Study 2, the most common adverse reactions reported in ≥5% of patients treated with LEQEMBI (N=898) and ≥2% higher than placebo (N=897) were infusion-related reactions (LEQEMBI: 26%; placebo: 7%), ARIA-H (LEQEMBI: 14%; placebo: 8%), ARIA-E (LEQEMBI: 13%; placebo: 2%), headache (LEQEMBI: 11%; placebo: 8%), superficial siderosis of central nervous system (LEQEMBI: 6%; placebo: 3%), rash (LEQEMBI: 6%; placebo: 4%), and nausea/vomiting (LEQEMBI: 6%; placebo: 4%).

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

Notes to Editors

1. About LEQEMBI^® (lecanemab-irmb)
Lecanemab 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 traditional approval by the U.S. Food and Drug Administration (FDA) on July 6, 2023. LEQEMBI is an amyloid beta-directed antibody indicated for Alzheimer's disease (AD) in the U.S. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment (MCI) 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. 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 MCI and mild dementia due to AD.

Please see full Prescribing Information, including Boxed WARNING in the United States.

Eisai has also submitted applications for approval of lecanemab in EU, China, Canada, Great Britain, Australia, Switzerland, South Korea and Israel. 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 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.

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 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.

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 Inc. 
At Eisai Inc., human health care (hhc) is our mission and is the shared purpose that connects us to those we serve creating a network of powerful relationships that enables us to identify, understand and work to address the needs of people throughout their lives. We boldly push past the boundaries of science and aim to deliver life-changing therapies and health-related solutions that matter to people and society. We bring together science, technology and real-world expertise to pursue a world free from cancer, Alzheimer's disease and other neurodegenerative diseases.

Everything we do is guided by the simple principle that patients and their families come first, and we have a responsibility to listen to and learn from them.

Eisai Inc. is the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd. The company's presence in the U.S. includes three discovery centers as well as commercial, clinical development and global demand organizations. To learn more about Eisai, please visit us at www.eisai.com/US and follow us on X and LinkedIn. For more updates on our work in neurology, please follow us on LinkedIn and X.

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.

We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media - X, 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.

SOURCE Eisai Inc.; Biogen Inc.