Eisai Completes Rolling Submission to US FDA for LEQEMBI® (lecanemab-irmb) Biologics License Application for Subcutaneous Maintenance Dosing for the Treatment of Early Alzheimer's Disease Under the Fast Track Status
Eisai has completed a rolling Biologics License Application (BLA) submission to the FDA for LEQEMBI® subcutaneous autoinjector for weekly maintenance dosing in early Alzheimer's disease treatment. The submission, under Fast Track designation, is based on data from the Clarity AD open-label extension study. If approved, patients could self-administer LEQEMBI at home in approximately 15 seconds after completing the initial biweekly intravenous phase. The autoinjector option aims to maintain effective drug concentrations while offering greater convenience compared to IV administration.
Eisai ha completato la presentazione di una domanda di licenza biologica (BLA) in modo progressivo alla FDA per l'autoiniettore sottocutaneo LEQEMBI® per la somministrazione settimanale nella cura dell'Alzheimer precoce. La presentazione, con designazione Fast Track, si basa su dati dello studio di estensione open-label Clarity AD. Se approvato, i pazienti potrebbero somministrarsi il LEQEMBI a casa in circa 15 secondi dopo aver completato la fase iniziale di infusione endovenosa bisettimanale. L'opzione dell'autoiniettore mira a mantenere concentrazioni efficaci del farmaco offrendo maggiore comodità rispetto alla somministrazione endovenosa.
Eisai ha completado la presentación de una Solicitud de Licencia Biológica (BLA) de manera gradual a la FDA para el autoinyector subcutáneo LEQEMBI® para la dosificación semanal en el tratamiento de la enfermedad de Alzheimer en etapas tempranas. La presentación, bajo la designación Fast Track, se basa en datos del estudio de extensión abierto Clarity AD. Si se aprueba, los pacientes podrán autoadministrarse LEQEMBI en casa en aproximadamente 15 segundos después de completar la fase intravenosa bisemanal inicial. La opción del autoinyector tiene como objetivo mantener concentraciones efectivas del fármaco mientras ofrece una mayor conveniencia en comparación con la administración intravenosa.
Eisai는 알츠하이머 초기 치료를 위한 주간 유지 요법의 피하 자가 주입기 LEQEMBI®에 대한 rolling Biologics License Application (BLA)을 FDA에 제출했습니다. Fast Track 지정 하에 이루어진 이번 제출은 Clarity AD 오픈 레이블 확장 연구 자료를 기반으로 합니다. 승인이 날 경우, 환자는 초기 2주 간의 정맥 주사 단계를 마친 후 약 15초 만에 자택에서 LEQEMBI를 자가 주입할 수 있게 됩니다. 자가 주입기 옵션은 정맥 주사에 비해 편리성을 높이면서 약물의 효과적인 농도를 유지하는 것을 목표로 하고 있습니다.
Eisai a complété une soumission progressive d'une Demande de Licence Biologique (BLA) auprès de la FDA pour l'autoinjecteur sous-cutané LEQEMBI® pour une administration hebdomadaire dans le traitement de la maladie d'Alzheimer précoce. La soumission, sous désignation Fast Track, est basée sur des données de l'étude d'extension ouverte Clarity AD. Si elle est approuvée, les patients pourraient s'auto-administrer LEQEMBI à domicile en environ 15 secondes après avoir terminé la phase initiale d'infusion intraveineuse bi-hebdomadaire. L'option d'autoinjecteur vise à maintenir des concentrations efficaces du médicament tout en offrant plus de commodité par rapport à l'administration intraveineuse.
Eisai hat die Einreichung eines schrittweisen Antrags auf biologische Lizenz (BLA) bei der FDA für den subkutanen Autoinjektor LEQEMBI® zur wöchentlichen Erhaltungstherapie bei frühestem Alzheimer abgeschlossen. Der Antrag, der unter der Fast Track-Bezeichnung eingereicht wurde, basiert auf Daten aus der Clarity AD offenen Verlängerungsstudie. Bei Genehmigung könnten Patienten LEQEMBI zu Hause in etwa 15 Sekunden nach Abschluss der initialen zweiwöchentlichen intravenösen Phase selbst verabreichen. Die Autoinjektor-Option zielt darauf ab, wirksame Medikamentenkonzentrationen aufrechtzuerhalten und gleichzeitig im Vergleich zur intravenösen Verabreichung mehr Komfort zu bieten.
- Fast Track designation received from FDA, potentially expediting review process
- New autoinjector format could enable home administration, reducing hospital visits
- Shorter administration time (15 seconds) compared to IV infusion
- Product already approved in multiple markets including US, Japan, China
- Still requires initial IV administration phase before switching to autoinjector
- FDA acceptance and PDUFA date pending
- Potential safety concerns including ARIA (amyloid-related imaging abnormalities)
Insights
The completion of Eisai's rolling BLA submission for LEQEMBI's subcutaneous autoinjector represents a significant advancement in Alzheimer's treatment delivery. The key advantages of this new administration method include:
- Reduced treatment time from current IV infusions to ~15 seconds for subcutaneous injection
- Potential for at-home administration, improving accessibility and reducing healthcare facility burden
- Weekly maintenance dosing that maintains effective drug concentrations
This development could significantly strengthen Biogen and Eisai's market position in the competitive Alzheimer's space. The subcutaneous autoinjector addresses key barriers to LEQEMBI adoption:
- Reduced healthcare resource utilization through potential home administration
- Improved convenience for patients and caregivers
- Lower administration costs compared to IV infusions
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, and the injection process is expected on average to take about 15 seconds. As part of the subcutaneous autoinjector 360 mg weekly maintenance regimen under review, patients who have completed the biweekly intravenous (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 of therapy even after plaque is cleared from the brain. This SC autoinjector is expected to be easier for patients and their care partners to use and may reduce the need for hospital or infusion site visits and nursing care compared to 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 approved in the
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.
* 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) |
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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 including Boxed WARNING.
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). Lecanemab is approved in the
LEQEMBI's approvals in these countries 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. 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
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, including 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.
U.S. Food and Drug Administration. 2023. FDA Converts Novel Alzheimer's Disease Treatment to Traditional Approval. Last accessed: October 2024.- Reuters. 2023.
Japan approves Alzheimer's treatment Leqembi by Eisai and Biogen. Last accessed: October 2024. - The Pharma Letter. 2024. Brief - Alzheimer drug Leqembi now approved in China. Last accessed: October 2024.
- Pharmaceutical Technology. 2024. South Korea's MFDS approves Eisai-Biogen's LEQEMBI for Alzheimer's. Last accessed: October 2024.
- Pharmaceutical Technology. 2024. Hong Kong approves Leqembi for Alzheimer's treatment. Last accessed: October 2024.
- BioSpace. 2024. Leqembi approved for the treatment of Alzheimer's disease in Israel. Last accessed: October 2024.
- United Arab Emirates Ministry of Health & Prevention. 2024. Registered Medical Product Directory. Leqembi. Last accessed: October 2024.
- BioSpace. 2024. Leqembi authorized for early Alzheimer's disease in Great Britain. Last accessed: October 2024.
- van Dyck, C., 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.
- 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.com/news/2022/news202285.html
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SOURCE Eisai Inc.
FAQ
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