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

"Unveiling Alzheimer's Disease (1901-2025): Historical Insights, Global Burden, Biological Mechanisms, Diagnostics, And Therapeutic Strategies". (PubMed, Ageing Res Rev) - "Therapeutically, the landscape has shifted from symptomatic treatments (e.g., cholinesterase inhibitors, memantine) to disease-modifying agents. Recent FDA approvals of monoclonal antibodies like Aducanumab, Lecanemab, and Donanemab mark a new era in targeted immunotherapy...Emerging drug delivery systems, including nanocarriers and intranasal formulations, aim to overcome the BBB and enhance therapeutic efficacy. The manuscript emphasizes the urgent need for integrative, personalized, and scalable solutions to manage AD's growing burden."

IO biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Mental Retardation • Psychiatry

Severe symptomatic amyloid-related imaging abnormalities in Alzheimer's disease: Two case reports and systematic review of reported cases. (PubMed, J Alzheimers Dis) - "Fifteen cases were associated with lecanemab, 10 with gantenerumab, 6 with donanemab, and 5 with other antibodies...Standardized diagnostic and therapeutic guidelines are needed to minimize ARIA-related morbidity and mortality.PROSPERO registration no. CRD420251055067."

Journal • Review • Alzheimer's Disease • CNS Disorders • Epilepsy • Hematological Disorders • Pain • APOE

Quebec will not publicly fund the first Health Canada-approved treatment for the underlying cause of Alzheimer’s disease after an expert committee concluded its benefits are too modest to improve patients’ lives (The Globe and Mail) - "The negative recommendation from Quebec’s National Institute for Excellence in Health and Social Services, known by the French acronym INESSS, marks the first time a government advisory body in Canada has evaluated whether the medication, lecanemab, should be paid for out of the public purse. The experts at INESSS rejected the drug without considering its price because they concluded lecanemab didn’t pass the first test of providing clear therapeutic value."

Reimbursement • Alzheimer's Disease

Radionuclide Selection Influences Imaging Outcomes in Immuno-PET with a Brain-Penetrating Anti-Amyloid-β Antibody. (PubMed, J Nucl Med) - "Lecanemab-Fab8D3 (Lec-Fab8D3), a bispecific amyloid-β (Aβ) antibody with enhanced brain delivery, may complement lecanemab immunotherapy as an immuno-PET imaging agent...Because of its residualizing properties, 89Zr produced the highest overall signal, whereas 124I yielded greater regional contrast, despite lower total brain signal. These findings enhance our understanding of the intrabrain distribution of bispecific antibodies and highlight the importance of radionuclide selection and its impact on immuno-PET outcomes."

IO Companion diagnostic • Journal • Alzheimer's Disease • CNS Disorders

Early Outcomes of Lecanemab for Alzheimer's Disease in the Veterans Health Administration. (PubMed, J Clin Med) - " Initial observations in a small VHA cohort suggest that uptake of lecanemab was limited, and the finding that nearly 30% of patients experienced ARIA or stroke within 7 months of initiation underscores the importance of monitoring the lecanemab safety and effectiveness long-term. These early findings should be interpreted cautiously given the limited sample size and very limited follow-up MoCA data."

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

Amyloid Beta in Alzheimer's Disease: Mechanisms, Biomarker Potential, and Therapeutic Targets. (PubMed, CNS Neurosci Ther) - "Incorporating new research findings and ongoing debates surrounding the Aβ cascade hypothesis is crucial for improving early diagnosis and for guiding the development of effective treatments for AD."

Biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • Metabolic Disorders • APP

Rapidly Progressive Dementia: Predictive Clues and a Proposed Diagnostic Approach Focused on Neurodegenerative Causes. (PubMed, Cureus) - "Conclusion Considering these factors, ND disorders-historically viewed as diagnoses of exclusion-may become a central component of the diagnostic approach to RPD, alongside autoimmune encephalitis (AE). We propose the development of an algorithm based on a predictive model that allows for the identification of a subgroup of patients in whom the diagnostic approach can be optimized, avoiding unnecessary studies and prioritizing the early identification of a possible ND etiology."

Journal • CNS Disorders • Dementia • Immunology

BioArctic AB's…partner Eisai announced today that Leqembi (lecanemab), has been included in the 'Commercial Insurance Innovative Drug List', recently introduced by the National Healthcare Security Administration (NHSA) of China (PRNewswire) - "The inclusion of Leqembi in this list marks a meaningful step toward expanding access to early Alzheimer's Disease (AD) treatment in China....The Commercial Insurance Innovative Drug List is scheduled to take effect on January 1, 2026."

Reimbursement • Alzheimer's Disease

Long-term safety and efficacy of lecanemab in early Alzheimer's disease: Results from the clarity AD open-label extension study. (PubMed, Alzheimers Dement) - "This research evaluated the long-term efficacy, safety, and HRQoL results from an ongoing extension of the phase 3 Clarity AD, which included open-label lecanemab treatment for up to 36 months. Overall, the results show participants continue to accrue a lecanemab treatment benefit up to 36 months and highlight the importance of continued long-term lecanemab treatment. Results presented in our paper demonstrate that lecanemab continued suppression of amyloid plaque levels and significantly slowed clinical decline on multiple measures of cognition, function, and quality of life in early AD at 18 months and continued for 36 months to date. No new safety signals were observed with continued lecanemab treatment. After the first 6 months, ARIA rates were low and similar to ARIA rates on placebo, with no association between ARIA occurrence and accelerated long-term clinical progression. Taken together with existing data, these results provide a clear rationale and a..."

Clinical • Journal • Alzheimer's Disease • CNS Disorders

Influence of patient characteristics on efficacy and safety of anti-amyloid monoclonal antibodies in Alzheimer's disease: A systematic review and meta-analysis. (PubMed, Ageing Res Rev) - "The efficacy and safety of lecanemab and donanemab varied across patient subgroups, including age, sex, race/ethnicity and genetic factors such as ApoE4 genotype status. The risk of ARIA was higher in ApoE4 carriers, particularly the homozygous."

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

Alzheimer's drug rejected for NHS use can 'slow disease' by 8 years (Manchester EveningNews) - "The spending watchdog deemed the benefits of lecanemab 'too small' to justify its cost, despite it being licensed for use in the UK."

Reimbursement • Alzheimer's Disease

Lecanemab Subcutaneous Formulation for Treatment Initiation in Early Alzheimer’s Disease: Optimizing Patient Care with a Potential New Option (Symposium Presentation: December 3, 3:10 PM PT) (GlobeNewswire) - "Eisai Presents New Data...at the Clinical Trials on Alzheimer’s Disease (CTAD) Conference 2025....In this symposium, the latest data from the lecanemab subcutaneous clinical development program were presented focusing on treatment initiation, including results from the subcutaneous (SC) formulation subcohort (n=273) in the Clarity AD trial OLE. It was shown that weekly administration of lecanemab SC-AI at 500 mg (two 250 mg injections) demonstrated bioequivalence in drug exposure compared to intravenous (IV) dosing of 10 mg/kg every two weeks (exposure ratio: 104%, 90% CI: 99.1%–109%)."

P3 data • Alzheimer's Disease

Estimating the 10-Year Time-Savings Benefits of Lecanemab Treatment (Presentation: December 3, 2:40 PM PT) (GlobeNewswire) - "Eisai Presents New Data...at the Clinical Trials on Alzheimer’s Disease (CTAD) Conference 2025....The time to progression from MCI due to AD to mild AD was 7.2 years in the untreated group, whereas with continued LEQEMBI treatment to the onset of moderate AD, progression to mild AD took 9.7 years, indicating a time savings of 2.5 years....The time to progression from MCI due to AD to moderate AD was 10.1 years in the untreated group, whereas with continued LEQEMBI treatment to the onset of moderate AD, progression to moderate AD took 13.6 years, indicating a time savings of 3.5 years."

Retrospective data • Alzheimer's Disease

Hippocampal Atrophy on Magnetic Resonance Imaging as a Surrogate Marker for Clinical Benefit and Neurodegeneration in Early Symptomatic Alzheimer's Disease: Synthesis of Evidence from Observational and Interventional Trials. (PubMed, CNS Drugs) - "These trials included four amyloid antibodies (aducanumab, lecanemab, donanemab, and gantenerumab) and one oral anti-oligomer agent (valiltramiprosate). HV on standardized vMRI is sensitive to anti-amyloid treatments, demonstrating strong correlations between slowed hippocampal atrophy and slowed cognitive decline. Data from over 23,000 subjects over three decades support HV as a surrogate marker for predicting clinical benefit in early symptomatic AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Modeling amyloid plaque turnover dynamics improves characterization of drug effects. (PubMed, Alzheimers Dement (N Y)) - "The model provides a fundamental measure of drug effects on plaque, independent of disease stage and study-design factors, improving cross-study comparisons and enabling predictions."

Journal • Alzheimer's Disease • CNS Disorders

New Data Presented at the Clinical Trials on Alzheimer’s Disease (CTAD) Conference 2025 Confirms Pharmacological Effect of LEQEMBI (lecanemab-irmb) on Neurotoxic Aβ Protofibrils in CSF (PRNewswire) - "In a CSF sub-cohort (n=410) of the Phase III Clarity AD study, total PF concentration in CSF was quantified using an ultrasensitive assay....Total CSF PF concentration in the placebo group increased by 19% at 12 months and 29% at 18 months. In contrast, the lecanemab group showed a 59% increase at 12 months and a 45% increase at 18 months. At 12 months, the difference compared with placebo was statistically significant (p=0.0126)....In the placebo group, a statistically significant correlation was observed between changes in CSF PF and changes in neurodegeneration biomarkers (total tau, neurogranin) as well as tau pathology biomarkers (p-tau181, MTBR-tau243) at baseline."

Biomarker • P3 data • Alzheimer's Disease

Evaluating amyloid-beta as a surrogate endpoint in trials of anti-amyloid-beta drugs in Alzheimer's disease: a Bayesian meta-analysis. (PubMed, J Comp Eff Res) - " Although our results from the analysis of data across all MABs suggested that Aβ was a potential surrogate endpoint for CDR-SOB, individually the surrogacy patterns varied across treatments and showed no evidence of association. Bayesian information-sharing revealed moderate surrogate relationship only for aducanumab and lecanemab."

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

Relationship between efficacy and preferential targeting of soluble Aβ aggregates. (PubMed, Alzheimers Dement (N Y)) - "These results suggest that selectivity for soluble toxic oligomers correlates with clinical efficacy, potentially attenuating monomer competition and amyloid-related imaging abnormalities (ARIA)."

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

Comparative efficacy and safety of symptomatic therapy and disease-modifying therapy for Alzheimer's disease: a systematic review and network meta-analysis. (PubMed, Front Neurosci) - "Aducanumab significantly improved ADAS-cog scores compared with placebo (MD -5.97, 95%CI -10.33, -1.61; SUCRA: 93.0%) and demonstrated notable improvements in ADCS-ADL scores (MD 4.99, 95%CI 2.27, 7.72; SUCRA: 98.6%). Memantine ranked highest for neuropsychiatric symptoms (SUCRA: 80.8%)...Lecanemab provides moderate benefits, while donanemab appears less effective. Thus, clinicians should apply disease-modifying therapies cautiously and individually, carefully balancing potential risks and benefits for each patient. PROSPERO [CRD42025637730], https://www.crd.york.ac.uk/PROSPERO/."

Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry

Microglial lipid droplets as therapeutic targets in age-related neurodegenerative diseases. (PubMed, NPJ Aging) - "Monoclonal antibodies approved for Alzheimer's disease (AD), such as lecanemab and aducanumab, have been shown to enhance microglial phagocytic function, underscoring the therapeutic relevance of microglia in neurodegenerative diseases (NDDs). We further propose a hypothetical mechanism by which LDs clearance restore energy metabolism, nuclear transport, facilitate DNA repair, suppress inflammation, and phagocytosis in microglia. Thus, elucidating LDs dynamics in microglia may provide novel therapeutic avenues for modifying the course of NDDs."

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

Advances in Neurological Therapies: A Review of Clinical Trials in Alzheimer's, Parkinson's, and Multiple Sclerosis. (PubMed, Am J Med) - "In Alzheimer's disease, anti-amyloid monoclonal antibodies (donanemab, lecanemab) achieved regulatory approval, establishing a new treatment paradigm despite modest efficacy and risks of amyloid-related imaging abnormalities (ARIA). In Parkinson's disease, GLP-1 receptor agonists (lixisenatide) demonstrated the first convincing disease modification signals in Phase II trials...Collectively, these findings herald a new era of disease-modifying therapy in neurology, though current gains remain limited and dependent on biomarker stratification and safety monitoring. The challenge ahead is translating these successes into accessible, sustainable clinical benefits."

Journal • Review • Alzheimer's Disease • CNS Disorders • Movement Disorders • Multiple Sclerosis • Parkinson's Disease

Amyloid-Related Imaging Abnormality complicated by intraparenchymal hemorrhage and seizure (AES 2025) - "Here we report a patient with ARIA who eventually developed intraparenchymal hemorrhage and seizures in the affected brain region. Case report A 73-year-old female was diagnosed with mild Alzheimer's type dementia and started on lecanemab infusions after an appropriate qualifying evaluation...Additionally, pulse dose glucocorticoids (IV methylprednisolone 1 g daily for 5 days) were given for treatment of cerebral edema...She was discharged on LEV and LCM as well as oral prednisone with a starting dose of 1 mg/ kg and gradual taper over 12 weeks. We report a patient who developed IPH and status epilepticus including three gelastic seizures as a complication of treatment with anti-amyloid therapy. We report a patient who developed IPH and status epilepticus including three gelastic seizures as a complication of treatment with anti-amyloid therapy. She responded well to ASM and glucocorticoid treatment. This case demonstrates a potential management approach to..."

Alzheimer's Disease • CNS Disorders • Dementia • Epilepsy • Hematological Disorders

Eisai…and Biogen…announced today that Eisai has filed a new drug application for 'LEQEMBI' (brand name, generic name: lecanemab) seeking approval for a subcutaneous formulation (subcutaneous autoinjector: SC-AI) as a new route of administration to Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) (GlobeNewswire) - "The application is based on data from multiple subcutaneous (SC) administration sub-studies of lecanemab conducted as part of the Phase 3 Clarity AD open-label extension (OLE), following the 18-month core study in individuals with Mild Cognitive Impairment (MCI) due to Alzheimer‘s disease (AD) or mild stage of AD dementia..."

Japan filing • Alzheimer's Disease • Dementia

Targeting Amyloid-β Proteins as Potential Alzheimer's Disease Therapeutics: Anti-Amyloid Drug Discovery, Emerging Therapeutics, Clinical Trials and Implications for Public Health. (PubMed, Pharmaceuticals (Basel)) - "We have evaluated the most recent developments in monoclonal antibodies, including aducanumab (discontinued November 2024), lecanemab, and donanemab, emerging therapeutic options, as well as emerging strategies such as tau-targeting therapies, gene therapy, and small molecule inhibitors. Moreover, we highlighted the challenges and opportunities in AD research, including the need for early diagnosis, personalized medicine, and combination therapies. Our review will offer a concise and informative overview of the current landscape and future directions in anti-Aβ therapeutics for AD, shedding light on potential treatments and prospects for improving patient outcomes."

Journal • Review • Alzheimer's Disease • CNS Disorders • Gene Therapies

Executive Summary of 2025 International Conference of the Korean Dementia Association and International Congress of the Asian Society Against Dementia (IC-KDA/ASAD 2025): A Report From the Academic Committee of the Korean Dementia Association. (PubMed, Dement Neurocogn Disord) - "Scientific highlights spanned the continuum from discovery to implementation: plasma and imaging biomarkers, retinal and electroencephalogram/voice-based digital biomarkers, and multimodal neuroimaging for risk stratification and outcome prediction; updates on anti-amyloid monoclonal antibodies (MABs) (lecanemab, donanemab), safety/amyloid-related imaging abnormalities management, and real-world data frameworks; mechanistic and multi-omics insights (genetics, metabolomics, epigenomics, transcriptomics); neuroinflammation and glia-mediated pathways; young-onset dementia cohorts across Asia-Pacific; vascular cognitive impairment trials and pathophysiology; neuropsychiatric symptoms and evidence-based behavioral and psychological symptoms of dementia care; lifestyle and multidomain prevention (Mediterranean-Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay-based interventions)..."

Journal • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Dementia • Hypertension • Inflammation • Psychiatry