Eisai Initiates Rolling Biologics License Application to US FDA for LEQEMBI® (lecanemab-irmb) for Subcutaneous Maintenance Dosing for the Treatment of Early Alzheimer's Disease Under the Fast Track Status
Eisai has initiated a rolling submission of a Biologics License Application (BLA) to the FDA for LEQEMBI (lecanemab-irmb) subcutaneous autoinjector for weekly maintenance dosing for early Alzheimer's disease. The BLA leverages data from the Clarity AD Study 301 and aims to allow home or medical facility administration, reducing the need for hospital visits compared to IV administration. LEQEMBI has gained approval in the U.S., Japan, and China, with more submissions pending globally. Concerns include amyloid-related imaging abnormalities (ARIA), which can cause serious side effects. Ongoing studies include AHEAD 3-45 and Tau NexGen for preclinical and dominantly inherited Alzheimer's, respectively.
- Initiation of rolling BLA to FDA for LEQEMBI subcutaneous autoinjector.
- Potential for home administration, reducing hospital visits.
- LEQEMBI approved in the U.S., Japan, and China.
- LEQEMBI reduced clinical decline by 27% at 18 months in Clarity AD Phase 3 trial.
- Statistically significant secondary endpoint benefits in ADCS-MCI-ADL scale.
- High incidence of ARIA potentially causing serious side effects.
- 0.7% incidence of intracerebral hemorrhage >1 cm with LEQEMBI compared to 0.1% with placebo.
- 3% incidence of serious ARIA in ApoE ε4 homozygotes.
- 2% discontinuation rate due to ARIA-H microhemorrhages.
- Ongoing requirement for careful ARIA monitoring and management.
Insights
Eisai's rolling submission of a Biologics License Application (BLA) to the FDA for LEQEMBI's subcutaneous maintenance dosing is significant for several reasons. This new delivery method could potentially improve patient compliance and convenience. Currently, treatments for Alzheimer's disease often require intravenous (IV) administration, which can be burdensome for patients and caregivers. A subcutaneous autoinjector reduces the need for frequent hospital visits, making the treatment more accessible and less time-consuming.
Moreover, subcutaneous administration maintains effective drug concentrations to sustain the clearance of toxic protofibrils, which are linked to cognitive decline in Alzheimer’s disease. This could provide sustained efficacy while potentially reducing adverse effects associated with IV administration, such as infusion reactions.
In terms of clinical impact, successful approval and adoption of this method could set a precedent for other Alzheimer's treatments, making disease management significantly more patient-friendly.
The announcement of Eisai's rolling submission to the FDA for a subcutaneous form of LEQEMBI could positively affect the stock prices of both Eisai and Biogen. The fast-track designation suggests an expedited review process, which means that the product could be available sooner than anticipated if approved. This can accelerate revenue generation and improve the companies' financial outlooks.
Market penetration is another critical aspect. As Eisai and Biogen plan to commercialize this product globally, including key markets such as the U.S., Japan and China, the potential market size is substantial. Alzheimer's disease has a high unmet need, making any improvement in treatment methods highly desirable. The convenience of a subcutaneous autoinjector could drive higher adoption rates, thereby boosting sales.
However, investors should also consider the costs involved in bringing this product to market, including regulatory hurdles, production costs and marketing expenses. While the upside potential is significant, these factors could impact short-term profitability.
The shift from intravenous to subcutaneous administration for LEQEMBI represents a meaningful advancement in patient care, particularly in the field of chronic disease management. This aligns with a broader trend in oncology and neurology to make treatments more patient-centric. The capability to maintain drug efficacy while reducing the strain on healthcare facilities and caregivers is notable.
Furthermore, the data supporting this application, derived from the Clarity AD open-label extension study, suggests that the new form not only maintains but potentially enhances the therapeutic benefits associated with continuous treatment. This could lead to better patient outcomes and overall disease management.
The convenience factor alone might lead to improved adherence to the treatment regimen, which is often a critical challenge in chronic conditions such as Alzheimer's disease.
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
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.1 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.2
INDICATION
LEQEMBI® [(lecanemab-irmb) 100 mg/mL injection for intravenous use] is indicated for the treatment of Alzheimer's disease (AD). 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.
IMPORTANT SAFETY INFORMATION
WARNING: AMYLOID-RELATED IMAGING ABNORMALITIES (ARIA) | ||
• | Monoclonal antibodies directed against aggregated forms of amyloid beta, including LEQEMBI, can cause 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 asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, rarely can occur. Serious intracerebral hemorrhages >1 cm, some fatal, have been observed with this class of medications. | |
• | Apolipoprotein E ε4 (ApoE ε4) Homozygotes: Patients who are ApoE ε4 homozygotes (~ | |
• | Consider the benefit of LEQEMBI for the treatment of AD and the potential risk of serious ARIA events when deciding to initiate treatment with LEQEMBI. | |
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, which can occur together. ARIA-E can be observed on magnetic resonance imaging (MRI) as brain edema or sulcal effusions and ARIA-H as microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with AD. With this class of medications, ARIA-H generally occurs in association with ARIA-E. Reported ARIA symptoms may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms usually resolve over time.
Incidence of ARIA
Symptomatic ARIA occurred in
ApoE ε4 Carrier Status and Risk of ARIA
Of the patients taking LEQEMBI,
Radiographic Findings
The majority of ARIA-E radiographic events occurred within the first 7 doses, although ARIA can occur at any time, and patients can have >1 episode. Maximum radiographic severity of ARIA-E with LEQEMBI was mild in
Intracerebral Hemorrhage
Intracerebral hemorrhage >1 cm in diameter was reported in
Concomitant Antithrombotic Medication:
In Clarity AD, 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
Other Risk Factors for Intracerebral Hemorrhage:
Patients were excluded from enrollment in Clarity AD 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). The presence of an ApoE ε4 allele is also associated with cerebral amyloid angiopathy. Caution should be exercised when considering the use of LEQEMBI in patients with factors that indicate an increased risk for intracerebral hemorrhage and in patients who need to be on anticoagulant therapy.
ARIA Monitoring and Dose Management Guidelines
Obtain a recent baseline brain MRI prior to initiating treatment with LEQEMBI and prior to the 5th, 7th, and 14th infusions. Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI. Depending on ARIA-E and ARIA-H clinical symptoms and radiographic severity, use clinical judgment when considering whether to continue dosing or to temporarily or permanently discontinue LEQEMBI. If a patient experiences ARIA symptoms, 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.
HYPERSENSITIVITY REACTIONS
Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred with LEQEMBI. 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 (IRRs)
IRRs were observed—LEQEMBI:
In the event of an IRR, the infusion rate may be reduced or the infusion may be discontinued and appropriate therapy initiated as clinically indicated. Consider prophylactic treatment prior to future infusions with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids.
ADVERSE REACTIONS
The most common adverse reaction leading to discontinuation of LEQEMBI was ARIA-H microhemorrhages that led to discontinuation in
The most common adverse reactions reported in ≥
Please see full Prescribing Information for LEQEMBI, including Boxed WARNING.
MEDIA CONTACTS | ||
Eisai Co., Ltd. Public Relations Department TEL: +81 (0)3-3817-5120 Eisai Inc. ( Julie Edelman 1-862-213-5915
EMEA Communications Department +44 (0) 786 601 1272 | Biogen Inc. Jack Cox + 1-781-464-3260 | |
INVESTOR CONTACTS | ||
Eisai Co., Ltd. Investor Relations Department TEL: +81 (0) 3-3817-5122 | Biogen Inc. Chuck Triano + 1-781-464-2442 |
Notes to Editors
1. About lecanemab (LEQEMBI®)
Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. It is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ).3 Lecanemab is approved in the
U.S. : For the treatment of Alzheimer's disease (AD). It should be initiated in patients with MCI or mild dementia stage of disease.3,7Japan : For slowing progression of MCI and mild dementia due to AD.5China : For the treatment of MCI due to AD and mild AD dementia.6
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.3 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 lecanemab reduced clinical decline on CDR-SB by
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 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
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 lecanemab development and regulatory submissions globally with both companies 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 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.
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 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. For audiences based in the
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.
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 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.
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; 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; and third party collaboration risks, 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
References
- 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
- 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.
- LEQEMBI. Prescribing information. Eisai Inc. 2023.
- US Food and Drug Administration. FDA Grants Accelerated Approval for Alzheimer's Disease Treatment. Available at: https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-disease-treatment. Last accessed: March 2024.
- Eisai Global. 2023. "LEQEMBI® Intravenous Infusion" (Lecanemab) Approved for the Treatment of Alzheimer's Disease in
Japan Available at: https://www.eisai.com/news/2023/news202359.html. Last accessed: March 2024. - Eisai Global. 2024. "LEQEMBI®" (Lecanemab) Approved for the Treatment of Alzheimer's Disease in
China . Available at: https://www.eisai.com/news/2024/news202403.html. Last accessed: March 2024. - 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.
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FAQ
What is the new application submitted by Eisai for LEQEMBI?
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What are the main study data supporting the LEQEMBI BLA?
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