Kisunla (donanemab-azbt) / Eli Lilly - 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

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

Donanemab in early symptomatic Alzheimer's disease: results from the TRAILBLAZER-ALZ 2 long-term extension. (PubMed, J Prev Alzheimers Dis) - P3 | "Over 3 years, donanemab-treated participants with early symptomatic AD demonstrated increasing clinical benefits and a consistent safety profile, with limited-duration dosing."

Journal • Alzheimer's Disease • CNS Disorders • Dementia

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

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

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

Care Partners' Perceptions of Amyloid-Targeting Therapy and Treat‑to‑Clearance for Alzheimer's Disease in Japan: A Qualitative Study. (PubMed, Neurol Ther) - "These results suggest that providing clear explanations and facilitating shared decision-making when introducing ATT, as well as introducing follow-up care and long-term evidence after stopping treatment, are needed."

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

Leveraging recent advances in plasma biomarkers to optimize early proof of concept trials in Alzheimer's disease. (PubMed, Alzheimers Dement (N Y)) - "Plasma pTau 181/217 at 6 months shows future promise to reasonably likely predict clinical benefit for drugs that reduce pTau 181/217 levels, supporting its use as a primary endpoint in early-phase trials. With effect sizes similar to those seen with donanemab, adequately powered trials may require as few as 100 participants. Such trials should include prespecified analyses to evaluate individual-level Prentice criteria, and pTau 181/217 results can be used to predict potential Phase 3 clinical outcomes."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders • Dementia

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

ALADDIN: Amyloid Lowering for Alzheimer's in Down's With Donanemab Investigation (clinicaltrials.gov) - P4 | N=60 | Not yet recruiting | Sponsor: Michael Rafii, MD, PhD | Trial completion date: Dec 2027 ➔ Dec 2028 | Initiation date: Dec 2025 ➔ Aug 2026 | Trial primary completion date: Dec 2027 ➔ Dec 2028

Trial completion date • Trial initiation date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Genetic Disorders

Data-driven modeling of amyloid-β targeted antibodies for Alzheimer's disease. (PubMed, NPJ Syst Biol Appl) - "The results indicate that Donanemab achieves the most significant reduction in fibrils. These findings provide a quantitative basis for optimizing AD treatments, providing valuable insight into the balance between therapeutic efficacy and safety."

Journal • Alzheimer's Disease • CNS Disorders

β-amyloid PET signal reduction in prior ARIA-E regions after anti-amyloid therapy for Alzheimer's disease. (PubMed, AJNR Am J Neuroradiol) - "Greater regional Aβ PET signal reduction in areas affected by ARIA-E may reflect enhanced local Aβ clearance, reduced tracer binding site availability, impaired glymphatic flow from immune complex deposition, or other mechanisms. The finding of greater regional Aβ PET signal reduction in ARIA-E regions refines the characterization of ARIA-E and raises the possibility that its occurrence may have beneficial as well as adverse implications."

Journal • Alzheimer's Disease • CNS Disorders

Drug repurposing for Alzheimer's disease: a Delphi consensus and stakeholder consultation. (PubMed, Alzheimers Res Ther) - "This Delphi consensus identified three high-priority drug repurposing candidates for AD with favourable safety profiles and mechanistic plausibility, which are considered suitable for pragmatic clinical trials, including remote or hybrid designs. The PROTECT platform, which supports international cohorts in the UK, Norway, and Canada, offers a well-established means to conduct such trials effectively, thus helping to accelerate the evaluation and potential deployment of these drug candidates to benefit individuals with or at risk for AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Herpes Zoster • Varicella Zoster

Effect of Alzheimer's disease medications on neurocognitive outcomes in children and adolescents with autism spectrum disorder and low IQ: a scoping review. (PubMed, Transl Psychiatry) - "This scoping review identified promising evidence of neurocognitive improvement in children and adolescents with ASD and low IQ following treatment with either a cholinesterase inhibitor or an NMDA receptor antagonist. Considering the lack of FDA-approved treatments for the cognitive deficits associated with ASD and an absence of medications approved to treat core features of ASD, our findings highlight an opportunity for innovative directions in autism research and treatment."

Journal • Review • Alzheimer's Disease • Autism Spectrum Disorder • CNS Disorders • Cognitive Disorders • Developmental Disorders • Genetic Disorders • Mental Retardation

ELI LILLY AND COMPANY (INDIA): CDSCO GRANTS MARKETING AUTHORIZATION FOR DONANEMAB FOR ADULTS IN EARLY STAGES OF ALZHEIMER’S (TradingView)

Approval • Alzheimer's Disease

Resting state alpha changes during monoclonal anti-amyloid treatment (Neuroscience 2025) - "Grant Support 5R01AG07934502 The U.S. Food and Drug Administration recently approved two monoclonal antibody therapies (mAbs), lecanemab and donanemab, for the treatment of early Alzheimer's disease (AD). Longitudinal data collection is ongoing. Data from future timepoints at Months 6 and 12, as well as data from additional participants, will inform a clearer pattern in occipital alpha changes over the course of treatment."

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

Inpp5d deficiency enhances microglial neuroprotective function in Alzheimer disease by inhibiting Amyloid-β plaque maturation and toxicity (Neuroscience 2025) - "While total Aβ burden remained unchanged, we observed significant reductions in thioflavin-positive plaques and N3pE-Aβ accumulation (a donanemab target)...In conclusion, INPP5D regulates the microglial-Aβ interaction patterns and microglial phenotypes, attenuating neuroprotective functions through promoting Aβ plaque maturation. These findings suggest that INPP5D inhibitors represent promising candidates for novel microglia-targeted AD therapeutics that could alter disease progression by enhancing neuroprotective functions of microglia."

Alzheimer's Disease • CNS Disorders • CX3CR1 • INPP5D • ITGAX

Brain-wide quantification of amyloid plaques, microglia, and disease modifying antibodies in AD model mice (Neuroscience 2025) - "Recent approvals of human IgG-based antibody therapeutics like Kisunla™ (Donanemab) for Alzheimer's Disease have invigorated R&D for CNS-targeting antibodies, highlighting a need for new approaches to assess the brain biodistribution and target engagement of large-molecule therapeutics in intact tissue samples...This study demonstrates the power of whole-brain tissue clearing, light sheet imaging, and automated quantification for assessing therapeutic distribution and disease-related phenotypes. Our pipeline provides a fast, unbiased, and anatomically comprehensive method for evaluating antibody therapeutic penetration and efficacy, supporting its use in preclinical development of Alzheimer's disease and other CNS-disease targeted therapeutics."

Preclinical • Alzheimer's Disease • CNS Disorders

A Study of Different Donanemab (LY3002813) Dosing Regimens in Adults With Early Alzheimer's Disease (TRAILBLAZER-ALZ 6) (clinicaltrials.gov) - P3 | N=1175 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: May 2025 ➔ May 2027

Trial completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Mental Retardation • Psychiatry

Eligibility for lecanemab and donanemab in Korea under Appropriate Use Recommendations. (PubMed, Alzheimers Dement) - "About a fourth of A+ patients in Korea met AUR criteria for anti-amyloid therapy. Donanemab eligibility slightly exceeded lecanemab despite narrower age criteria. MMSE z-score adjustment increased eligibility in older, less-educated individuals. Over 30% of eligible patients were excluded due to ARIA-related MRI findings. Culturally adapted cognitive thresholds are essential for equitable treatment access."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • APOE

Using Propensity Weighting Methods With Real-World Data and Noncontrolled Extension Data From a Clinical Trial to Estimate Long-Term Treatment Effect: An Example in Alzheimer's Disease (ISPOR-EU 2025) - "Our analyses indicate that donanemab-treated patients continue to progress more slowly than untreated patients over 36 months, and provide further evidence for modelling long-term treatment effect in cost-effectiveness models."

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