Leqembi (lecanemab-irmb) / Biogen, BioArctic, Eisai - LARVOL DELTA

Antiamyloid Monoclonal Antibodies in Alzheimer's Disease, Part 1: Patient Selection. (PubMed, J Neuropsychiatry Clin Neurosci) - "Food and Drug Administration approvals for the monoclonal antibody-based medications lecanemab and, more recently, donanemab provide clinicians with two antiamyloid therapy (AAT) options for targeting early symptomatic AD. Patient selection is complex, and although appropriate-use recommendations have been published, clinicians caring for patients with AD across the United States face uncertainty when trying to align clinical trial criteria, appropriate-use recommendations, and real-world patients in the clinic. Practical issues in patient selection as well as health care and systemic challenges in the implementation of AAT are considered in part 1 and part 2, respectively, of this two-part Treatment in Behavioral Neurology & Neuropsychiatry commentary on these therapies from the American Neuropsychiatric Association Dementia Special Interest Group."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Psychiatry

Characterizing the Journey of Early Alzheimer's Disease in Patients Initiating Lecanemab Treatment in the United States: A Real-World Evidence Study. (PubMed, Neurol Ther) - "Lecanemab was utilized in appropriate patient populations according to the prescribing information approved by the US Food and Drug Administration. Findings from our study provide first insights into the real-world use of lecanemab in the USA and shed light on the need for increased and timely lecanemab initiation for the long-term management of early AD."

HEOR • Journal • Real-world evidence • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Alzheimer's disease patient brain extracts induce multiple pathologies in novel vascularized neuroimmune organoids for disease modeling and drug discovery. (PubMed, Mol Psychiatry) - "Furthermore, after treatment with Lecanemab, an FDA-approved antibody drug targeting Aβ, AD brain extracts exposed organoids showed a significant reduction of amyloid burden, along with an elevated vascular inflammation response. Thus, the vascularized neuroimmune organoid model provides a unique opportunity to study AD, particularly sAD, under a pathophysiological relevant three-dimensional (3D) human cell environment. It also holds great promise to facilitate AD drug development, particularly for immunotherapies."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • Dementia • Inflammation

The efficacy and safety of anti-amyloid monoclonal antibody versus acetylcholinesterase inhibitor with an in-depth analysis across genotypes and disease stages: a systematic review and meta-analysis. (PubMed, J Prev Alzheimers Dis) - "mABs were associated with a slower progression of cognitive decline than AChEIs; however, this effect did not reach the MID. The incidence of ARIA-E with mABs was associated with APOE4 carrier status and was not indicative of treatment efficacy."

Journal • Retrospective data • Alzheimer's Disease • CNS Disorders • Dementia • Hematological Disorders • APOE

Lecanemab Associated Status Epilepticus and Psychosis With Serious ARIA-E (Amyloid Related Imaging Abnormalities - Edema): Case Report (ATS 2025) - "In the emergency department she was noted to have tonic-clinic seizures concerning for status epilepticus and was treated with lorazepam and levetiracetam along with endotracheal intubation for airway protection. In patients who developed ARIA during Lecanemab clinical trials, most cases were asymptomatic with mild to moderate radiographic severity; however, serious and/or fatal symptoms have now been reported and require further research. In clinical trials, resolution of ARIA occurred within 4 months in majority of cases."

Case report • Clinical • Alzheimer's Disease • CNS Disorders • Dementia • Epilepsy • Psychiatry

Eligibility for Lecanemab Treatment in the Republic of Korea: Real-World Data From Memory Clinics. (PubMed, J Clin Neurol) - "Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education."

Journal • Real-world evidence • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Re-evaluation of the efficacy and safety of anti-Aβ monoclonal antibodies (lecanemab/donanemab) in the treatment of early Alzheimer's disease. (PubMed, Front Pharmacol) - "Among other adverse events, the risk of superficial siderosis of the central nervous system was notably higher and statistically significant. Lecanemab/Donanemab can improve memory, cognitive function, and daily living abilities in patients with early AD, significantly reduce the composite score of Alzheimer's disease, and inhibit the accumulation of amyloid peptides, thereby alleviating symptoms and improving the condition."

Journal • Review • Alzheimer's Disease • CNS Disorders

Role of External Control Arm (ECA) Derived from Real World Data (RWD) in US FDA Regulatory Approval from 2020-2024 (ISPOR 2025) - "OBJECTIVES: To analyze role of ECA in US FDA approvals ( 2020 - 2024) & summarize the key disease areas leveraging ECA. systematic literature review and analysis of all novel drug approvals including NDA (New Drug Application) and BLA (Biological License Application)submitted from 2020-2024 were analyzed. The percentage of approvals involving external control arms increased steadily, particularly in rare diseases, oncology, and conditions with small or hard-to-recruit patient populations from 2020-2024 2020: Early Exploration (5-7% of Approvals) : 1.Ibrance (palbociclib): Used retrospective RWD to support male breast cancer indication...Blincyto (blinatumomab): Supplemental approvals for rare cancers based on external data. 2021: Accelerated Adoption Amid COVID-19 (10-15% of Approvals) 1.Veklury (remdesivir): Approval supported by real-world hospital data as external comparisons...Keytruda (pembrolizumab): Label expansion for certain cancers using external control..."

Clinical • Real-world • Real-world evidence • Alzheimer's Disease • Breast Cancer • CNS Disorders • Genetic Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Male Breast Cancer • Movement Disorders • Muscular Atrophy • Novel Coronavirus Disease • Oncology • Rare Diseases • Solid Tumor • HER-2

Summary of Evolving Role and Impact of Real World Evidence (RWE) in US FDA Regulatory Approvals (2020-2024) (ISPOR 2025) - "Notable cases like Rozlytrek (entrectinib) for rare cancers leveraged synthetic control arms, Zolgensma (onasemnogene abeparvovec-xioi) used RWE for expanded indications...Examples include Enhertu (fam-trastuzumab deruxtecan-nxki) for HER2-low breast cancer and Evrysdi (risdiplam) for spinal muscular atrophy, supported by longitudinal real-world data. 1) 2020, RWE was primarily used in label expansions and post-marketing safety evaluations, particularly in oncology and rare diseases. Notable approvals included Ibrance (palbociclib) for male breast cancer, based on real-world data from EHRs.2) 2021, during COVID-19 pandemic, RWE played a key role in Emergency Use Authorizations (EUAs) and full approvals of treatments like Veklury (remdesivir). The % of approvals involving RWE increased to 15-20%, with RWE supporting label expansions for drugs like Keytruda (pembrolizumab).3)2022, RWE contributed to 25-30% of approvals, including initial NDAs and BLAs."

Clinical • HEOR • Real-world • Real-world evidence • Alzheimer's Disease • Breast Cancer • CNS Disorders • Genetic Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Male Breast Cancer • Movement Disorders • Muscular Atrophy • Novel Coronavirus Disease • Oncology • Rare Diseases • Solid Tumor • HER-2

MHRA to evaluate monthly intravenous maintenance dosing of Leqembi for the treatment of early Alzheimer’s disease in the UK (Cision) - "BioArctic AB’s...partner Eisai today announced that the Medicines and Healthcare Products Regulatory Agency (MHRA) have validated and will now evaluate a proposed Marketing Authorisation Variation for monthly lecanemab dosing in the United Kingdom....The proposed intravenous maintenance dosing variation application offers the possibility to reduce lecanemab infusion frequency from every two weeks to every four weeks for eligible adult patients with early Alzheimer’s disease in the UK after the initial 18 months of treatment of the currently approved dosing regimen."

MHRA filing • Alzheimer's Disease

Lecanemab and Anticoagulants: Projected Effects on Health and Quality of Life. (PubMed, medRxiv) - "Using inputs from the literature, we modeled increased ICH risk with lecanemab (2.02-fold), apixaban (1.84-fold), and lecanemab/apixaban interaction (2.67-fold). There was greater equipoise across treatment strategies for persons 65-74 years, for whom improved estimates of the ICH risk and lecanemab-anticoagulant interaction are critical to identifying the preferred strategy. National Institute on Aging/National Institutes of Health (K76AG074919, P30AG062421, U01AG076478, and R01AG069575)."

HEOR • Journal • Alzheimer's Disease • Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

The Role of Patient-Reported Outcomes in US FDA Novel Drug Approvals and Reimbursement Decisions (2020-2024) (ISPOR 2025) - "Rinvoq (AbbVie) - PRO data showed improved quality of life in rheumatoid arthritis, contributing to $2.3 billion...Zeposia (Bristol-Myers Squibb) - PROs on fatigue reduction generated $500 million. Imcivree (Rhythm Pharmaceuticals) - PRO data supported FDA approval 2022: FDA : 37 drugs, with 30% (11 drugs) Reimbursement : 85 total approvals, with 35% (30 approvals) Adbry (LEO Pharma) - PROs on itch reduction generated $90 million . Camzyos (Bristol-Myers Squibb) - Symptom relief PROs were key 2023: FDA : 49 drugs, with 33% (16 drugs) Reimbursement 95 total approvals, with 45% (43 approvals. Leqembi (Eisai/Biogen) - FDA approval and Medicare conditional reimbursement for Alzheimer's disease leveraged PROs on cognitive function improvements, generating $200 million/ Jaypirca (Eli Lilly) - Patient-reported symptom relief supported FDA and payer decisions for mantle cell lymphoma... The inclusion of PROs in FDA novel drug approvals increased from 18% in 2020 to 40% in..."

Clinical • Patient reported outcomes • Reimbursement • US reimbursement • Alzheimer's Disease • CNS Disorders • Fatigue • Hematological Malignancies • Immunology • Infectious Disease • Inflammatory Arthritis • Lymphoma • Mantle Cell Lymphoma • Oncology • Rheumatoid Arthritis • Rheumatology

Coverage Gaps: Do U.S. Commercial Health Plans Have Concordant Alzheimer's Disease Therapy & Testing Policies? (ISPOR 2025) - "These policies were effective from 1/1/2024 through 12/31/2024 and included FDA-approved therapies (lecanemab and donanemab) and testing for amyloid pathology (cerebrospinal fluid [CSF] biomarker assays and amyloid positron emission tomography [PET] scans). Although there's often alignment between amyloid targeting therapies and testing policies, inconsistencies remain. As new technologies like plasma-based biomarkers become available, it's essential for health plans to ensure policy concordance to minimize access variability for AD patients."

Discordant • HEOR • Alzheimer's Disease • CNS Disorders

Evaluating the Transition from Intravenous to Subcutaneous Formulations: A Cost-Comparison Model for Early Alzheimer's Disease (ISPOR 2025) - "Subcutaneous administration of lecanemab potentially offers substantial cost-savings from a societal perspective, reducing treatment, time, and QOL-associated costs for both patients and caregivers. These findings underscore the potential value of SC formulations in improving treatment delivery and mitigating the economic burden of AD."

HEOR • Reimbursement • US reimbursement • Alzheimer's Disease • CNS Disorders

Cost-Effectiveness of Delaying Progression of Alzheimer's Disease with Novel Monoclonal Antibodies: A Societal Perspective (ISPOR 2025) - "This research aims to estimate the cost impact and cost-effectiveness of Aducanumab, Donanemab, and Lecanemab in delaying progression in early AD patients. A Markov simulation model was used incorporating literature and a prior cost-impact model of delaying AD progression. New monoclonal AD treatments were estimated to add substantial costs with modest clinical benefits, with Donanemab adding the highest cost. The cost-effectiveness of the agents is substantially influenced by the patient's age at treatment initiation, treatment efficacy in slowing disease progression, and the cost of medications."

Cost effectiveness • HEOR • Alzheimer's Disease • CNS Disorders

How to Mitigate "Carer QALY Trap" when Including Caregiver QOL in Cost-Effectiveness Analysis: A Model Simulation Using Lecanemab in Japanese Patients with Alzheimer's Disease (ISPOR 2025) - "Extending the time that patients remain in the early stages of AD should also be beneficial for caregivers. However, under the decrement approach, the longer a patient remains in the early stage of AD, the longer disutility are added to caregivers, who then accrue negative QALYs. This can lead to counterintuitive results when expressing results in terms of QALYs."

Clinical • Cost effectiveness • HEOR • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Psychiatry

Markov Simulation for Estimating the Impact of Lecanemab Treatment on Health Outcomes in Early Alzheimer's Disease from a Japanese Societal Perspective (ISPOR 2025) - "LEC delayed disease progression in Japanese patients with early AD, preserving their independence longer."

HEOR • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Adverse Events Associated With Recently Approved Alzheimer's Drugs: A Real-World Pharmacovigilance Study (ISPOR 2025) - "Aducanumab, lecanemab, and donanemab were recently approved therapies targeting beta-amyloid removal in the brain. FDAERs provide a rapid understanding of Real-world safety signals for AD therapies which demonstrated similar overall organ-level adverse effects, however distinct differences in specific events were noted."

Adverse events • Clinical • Real-world • Real-world evidence • Alzheimer's Disease • Cerebral Hemorrhage • CNS Disorders • Fatigue • Hematological Disorders • Pain

Feasibility of Replicating a Published Health Economic Model From an ICER Report Using Generative AI (ISPOR 2025) - "Python facilitated large language model interactions, and the extracted parameters were implemented in the Heemod package in R to construct and run the Markov model, comparing Lecanemab+supportive-care against supportive-care-alone... This study demonstrates the feasibility of using Generative AI to replicate complex health economic models. While it showcases Generative AI's ability to approximate key outcomes, it also highlights the dependency on the clarity and completeness of model inputs,, emphasizing the need for standardized reporting in HEOR. Future research should replicate more decision-analytic models to validate and refine this approach."

HEOR • Alzheimer's Disease • CNS Disorders • KEAP1

A real-world pharmacovigilance study of adverse drug reactions associated with lecanemab and aducanumab based on WHO-VigiAccess and FAERS databases. (PubMed, Front Pharmacol) - "However, Lecanemab showed a lower risk of ARIA, cerebral hemorrhage, and severe events. These findings emphasize the need for further clinical research to clarify the long-term safety and efficacy of both drugs."

Adverse drug reaction • Adverse events • Journal • Real-world evidence • Alzheimer's Disease • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Pain

Metabolic Regulation as a Potential Therapeutic Approach for Alzheimer's Disease. (PubMed, Curr Alzheimer Res) - "Lecanemab, a therapeutic antibody designed to target amyloid-beta (Aβ) clearance, has recently been approved by the FDA and introduced in multiple countries, representing a significant milestone in advancing Alzheimer's disease (AD) treatment...Emerging evidence suggests that glucose and lipid metabolism dysfunction plays a critical role in AD, with metabolic changes emerging as one of the most significantly altered pathways in the early stage of pathology. These findings highlight the therapeutic potential of targeting metabolic regulation as a strategy to address AD."

Journal • Alzheimer's Disease • CNS Disorders • Metabolic Disorders

Response to Xing et al.: post-marketing safety concerns with Lecanemab: a pharmacovigilance study based on the FDA adverse event reporting system database. (PubMed, Alzheimers Res Ther) - "The reports in the FDA database have significant limitations, including submission of incomplete, inaccurate, untimely, duplicate, relatedness to drug uncertainty, and/or unverified information. Therefore, broader generalizations, clinical conclusions, and treatment recommendations should not be made based solely on FAERS databases analyses."

Adverse events • Journal • P4 data

Adverse events associated with lecanemab: A disproportionality analysis of data from the FDA adverse event reporting system. (PubMed, J Alzheimers Dis) - "These findings underscore the importance of ongoing monitoring and research to enhance lecanemab's safety profile in AD treatment. However, due to the limitations of FAERS, our analysis is imperfect in terms of important AEs such as therapy-related brain loss and death."

Adverse events • Journal • Alzheimer's Disease • CNS Disorders • Mental Retardation • Pain • Psychiatry

Lecanemab: Experts criticise European Commission approval of Alzheimer's drug. (PubMed, BMJ) - No abstract available

European regulatory • Journal • Alzheimer's Disease • CNS Disorders

Concerns about the approval of lecanemab for Alzheimer's disease. (PubMed, BMJ) - No abstract available

Journal • Alzheimer's Disease • CNS Disorders