solanezumab (LY2062430) / Eli Lilly - LARVOL DELTA

Scalable Markers for Early Cognitive Decline: Plasma p-tau217, Subjective Cognitive Concerns, and Digital Testing: Results from the A4/LEARN studies. (PubMed, medRxiv) - "We analyzed 1,071 cognitively unimpaired adults aged 65-85 years from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial (amyloid-positive; solanezumab or placebo arms) and the parallel Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) cohort (amyloid-negative)...Together, these non-invasive and scalable measures provide practical tools for risk stratification years before clinical diagnosis. Combining biological, subjective, and digital markers may support earlier detection in clinical care and enhance efficiency in prevention trial enrollment."

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=490 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting

Biomarker • Enrollment closed • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Replacement of a single residue in an antibody abolishes cognate antigen binding, as predicted by theoretical methods. (PubMed, Comput Struct Biotechnol J) - "We applied this approach to analyze the binding of solanezumab to synthetically produced Aβ variants and Aβ catched by the iRS functionalized surface from cerebrospinal fluid, showcasing its utility in Alzheimer's disease diagnostics. These findings highlight the value of computational modeling and experimental validation in understanding antigen-antibody interactions, with significant implications for diagnostic and therapeutic applications."

Journal • Alzheimer's Disease • CNS Disorders

MRI-based multi-organ clocks for healthy aging and disease assessment. (PubMed, Nat Med) - "Finally, participants with more youthful versus more aged brain profiles exhibited distinct cognitive decline trajectories over 240 weeks of treatment with the Alzheimer's disease drug solanezumab, although this heterogeneity cannot be fully attributed to the drug. In summary, we developed seven MRIBAGs that enhance the existing multi-organ biological aging framework, and we demonstrate their clinical potential to advance aging research."

Journal • Aesthetic Medicine • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Diabetes • Metabolic Disorders

NEW DISCOVERIES IN AMYLOID-RELATED IMAGING ABNORMALITIES WITH HEMORRHAGE AND ANTI-AMYLOID BETA MONOCLONAL ANTIBODIES (WCN 2025) - "(5)Amyloid Beta Clearance Rate. The risk of ARIA-H, from highest to lowest, is as follows: Donanemab, Aducanumab, Bapineuzumab, Lecanemab, Gantenerumab, Crenezumab, Solanezumab. This research enhances our understanding of ARIA-H and may guide future monoclonal antibody drug development, which may improve the cognition and overall prognosis of Alzheimer's disease patients."

Alzheimer's Disease • CNS Disorders

EFFICACY OF ANTI-AMYLOID-Β ANTYBODIES IN ALZHEIMER'S DISEASE: A NETWORK META-ANALYSIS OF COGNITIVE AND FUNCTIONAL OUTCOMES (WCN 2025) - "Background and Aims: Monoclonal antibodies against amyloid-β in Alzheimer's disease (AD) treatments show variable efficacy. Although Donanemab shows the highest cognitive and functional decline delay, it is not significant due to the low number of study. Solanezumab, gantenerumab 510 mg, and aducanumab demonstrates cognitive improvements on the ADAS-Cog 13-item scale. No anti-Aβ antibody showed a significant benefit in slowing functional decline."

Retrospective data • Alzheimer's Disease • CNS Disorders

Use of monoclonal antibodies in Alzheimer's disease - a systematic review of phase III clinical trials (ECNP 2025) - "Current pharmacological treatments available in Portugal include cholinesterase inhibitors: Rivastigmine, Galantamine, Donepezil, and the N-methyl-D-aspartate (NMDA) receptor antagonist Memantine (2). There was insufficient evidence to conclusively determine the effectiveness of monoclonal antibodies in significantly delaying AD progression. While Aducanumab has shown some promise at higher doses in specific trials, inconsistencies across studies highlight the need for further investigation. The failure of Crenezumab, Gantenerumab, and Solanezumab to achieve meaningful clinical benefits underscores the challenges of targeting amyloid beta in AD therapy."

Clinical • P3 data • Review • Alzheimer's Disease • CNS Disorders • Dementia • Psychiatry

Anti-amyloid monoclonal antibody therapies in Alzheimer's disease - a scoping review. (PubMed, Neuroscience) - "Across the sample, reductions in amyloid burden were frequently reported (10 trials), with a smaller subset of studies reporting significant cognitive and functional improvements (4 trials), primarily lecanemab and aducanumab in addition to one pooled analysis of solanezumab. This review highlights the need for rigorous, diverse, and patient-centered research. Addressing these gaps is critical in ensuring safe, effective, and equitable treatment for all patients living with Alzheimer's disease."

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

Multimodal prognostic modeling of individual cognitive trajectories to enhance trial efficiency in preclinical Alzheimer's disease. (PubMed, Alzheimers Dement) - P3 | "Prognostic models can predict decline in preclinical AD and improve trial efficiency."

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

The relationship of soluble tau species with Alzheimer's disease amyloid plaque removal and tau pathology. (PubMed, Alzheimers Dement) - P2/3 | "p-tau217 and p-tau231 correlate with Aβ-PET and respond to Aβ-plaque lowering therapies. Aβ immunotherapy trials support a direct link between p-tau changes and Aβ plaques Gantenerumab reduces Aβ plaques but does not affect tau NFT-related biomarkers. Blood-based p-tau217 assays may provide a non-invasive tool to monitor Aβ therapies. MTBR-tau243 strongly correlates with tau PET and tracks NFT pathology progression. Further studies are needed to validate tau biomarkers for tracking NFT-targeting therapies."

Biomarker • Clinical • IO biomarker • Journal • Alzheimer's Disease • CNS Disorders

Structural and Functional Determinants of ARIA-H Risk in Anti-Amyloid Monoclonal Antibodies: A Comparative Mechanistic Framework for Alzheimer's Immunotherapy Development. (PubMed, Curr Neuropharmacol) - "These findings establish a mechanistic framework for ARIA-H risk and provide concrete molecular predictors to guide antibody engineering strategies. Prioritizing mAbs with controlled amyloid clearance, C-terminal binding domains, and IgG1 frameworks may enhance therapeutic safety, advancing precision immunotherapy for Alzheimer's disease."

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

The structural foundations of anti-amyloid-β immunotherapies: Unravelling antibody-antigen interactions in Alzheimer's disease treatment. (PubMed, J Alzheimers Dis) - "BackgroundAnti-amyloid-β (Aβ) immunotherapies are emerging as treatments for Alzheimer's disease (AD).ObjectiveThis review examines the structure-activity relationships of anti-Aβ therapeutics tested in phase 3 trials.MethodsWe analyzed crystallographic data and molecular models to elucidate the Aβ binding mechanisms of donanemab, lecanemab, aducanumab, bapineuzumab, gantenerumab, solanezumab, and crenezumab.ResultsLecanemab recognizes minimally degraded Aβ missing 1-2 residues, avoiding common Aβ in circulation and further degraded material sequestered in plaques. This focal point may account for the significant cognitive effects of lecanemab. The structure of aducanumab suggests a broadly neutralizing role has evolved for natural immunity to AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Vascular Neurology • APOE

The Efficacy of Solanezumab in Patients with Alzheimer's Disease: A Systematic Review and Meta-Analysis of Clinical Trials. (PubMed, Pharmaceutics) - " While solanezumab may offer slight benefits in general cognitive performance, its overall impact on clinically meaningful outcomes remains limited. The results do not support its use as a disease-modifying therapy for Alzheimer's disease in either preclinical or symptomatic stages."

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

Multi-organ AI Endophenotypes Chart the Heterogeneity of Pan-disease in the Brain, Eye, and Heart. (PubMed, medRxiv) - "Crucially, in data from an anti-amyloid AD drug (solanezumab 6 ), heterogeneity in cognitive decline trajectories was observed across treatment groups. Finally, Heart 1 and Heart 2 had the highest mortality risk and unique medication history profiles, with Heart 1 showing favorable responses to antihypertensive medications and Heart 2 to digoxin treatment. The 11 MAEs provide novel AI dimensional representations for precision medicine and highlight the potential of AI-driven patient stratification for disease risk monitoring, clinical trials, and drug discovery."

Heterogeneity • Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Heart Failure • Migraine • Oncology • Pain

Incremental Value of Plasma Biomarkers in Predicting Clinical Decline Among Cognitively Unimpaired Older Adults: Results from the A4 trial. (PubMed, medRxiv) - "The sample included 866 cognitively unimpaired, amyloid-positive individuals from the A4 trial (comprising participants randomized to receive Solanezumab or placebo) and 343 cognitively unimpaired, amyloid-negative individuals from LEARN...Plasma P-tau217 and ADCS-PACC, individually and in combination, improved prediction of cognitive/functional decline in asymptomatic older adults. Predictive models incorporating these scalable and non-invasive measures improved clinical trial enrichment and earlier identification of at-risk individuals preclinical AD."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders • Dementia • Aβ42 • GFAP

Evaluation of Amyloid Removal as a Surrogate for Cognitive Decline: Pilot Analysis in Individual-Level Data from the A4 Study of Solanezumab. (PubMed, medRxiv) - "Amyloid removal has been used as a surrogate outcome in Alzheimer's disease trials, allowing accelerated approval of aducanumab and lecanemab. Estimates showing near-zero effects of amyloid reduction on cognitive decline suggest minimal impact of amyloid reduction in populations with little disease progression. Replication in anti-amyloid trials with larger treatment effects could guide treatment and regulatory decisions."

Journal • Alzheimer's Disease • CNS Disorders

Multi-organ MRI digitizes biological aging clocks across proteomics, metabolomics, and genetics. (PubMed, medRxiv) - "Finally, we demonstrate the clinical relevance of the 7 MRIBAGs in predicting disease endpoints (e.g., diabetes mellitus), all-cause mortality, and capturing differential and heterogeneous cognitive decline trajectories over 240 weeks of treatment with the Alzheimer's disease drug (Solanezumab). Sex differences are evident across multiple organ systems, manifesting at structural, molecular, and genetic levels. In summary, we developed 7 MRI-based aging clocks that enhance the existing multi-organ biological aging framework, offer multi-scale insights into aging biology, and demonstrate clinical potential to advance future aging research."

Journal • Aesthetic Medicine • Alzheimer's Disease • CNS Disorders • Diabetes • Metabolic Disorders

Data Driven Modelling for Clinical Trials on Alzheimer's Disease (OHBM 2025) - "The A4 Study has bucked this trend — all data became available in July 2024 from this secondary prevention clinical trial of solanezumab in preclinical Alzheimer's disease...Treatment response differed between subgroups, with one subtype showing a trend towards treatment efficacy. I'll discuss the implications of this and explore how data-driven brain mapping can be incorporated into clinical trial design."

Clinical • Alzheimer's Disease • CNS Disorders

Immunohistochemical evaluation of a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease. (PubMed, Acta Neuropathol) - "Our results demonstrate with direct histologic evidence that gantenerumab treatment in DIAD can reduce parenchymal Aβ deposits throughout the brain in a dose-dependent manner, suggesting that more complete removal may be possible with earlier and more aggressive treatment regimens. Although AFs of tauopathy, microgliosis, and astrocytosis showed no clear response to partial Aβ removal in this limited autopsy cohort, future examination of these cases with more sensitive techniques (e.g., mass spectrometry) may reveal more subtle 'downstream' effects."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Aβ42 • CSF Aβ42 • GFAP

Changes in Daily Functioning in Association With Tau and Amyloid Among Unimpaired Older Adults With and Without Elevated Amyloid. (PubMed, Neurology) - P, P3 | "Higher tau levels are associated with the fastest decline in everyday functioning in the presence of elevated amyloid, and those accumulating more tau show a faster decline in everyday functioning. These findings demonstrate the utility of including sensitive measures of everyday functioning in clinical practice and clinical trials at the stage of preclinical AD."

Clinical • Journal • Alzheimer's Disease • CNS Disorders

The Efficacy of Anti-amyloid Monoclonal Antibodies in Early Alzheimer's Dementia: A Systematic Review. (PubMed, Ann Indian Acad Neurol) - "Our findings highlight the need to consider the complex pathophysiology of AD in treatment development. Focusing solely on the amyloid-beta hypothesis may be inadequate; further research is necessary to understand the underlying mechanisms and develop treatments for the multifactorial nature of the disease."

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

Predicting Cognitive Decline Using Baseline Data in Cognitively Unimpaired Older Adults: Results from the A4 Trial (P2-3.018). (PubMed, Neurology) - "Participants included 1169 amyloid-positive participants enrolled in the A4 trial (receiving solanezumab, N=578, or placebo, N=591), and 538 amyloid-negative individuals enrolled in the LEARN observational study...The institution of Dr. Ezzati has received research support from Cure Alzheimer's Fund."

Clinical • Journal • Alzheimer's Disease • CNS Disorders

Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer's disease: an open-label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU trial. (PubMed, Lancet Neurol) - P2/3 | "Partial or short-term amyloid removal did not show significant clinical effects. However, long-term full amyloid removal potentially delayed symptom onset and dementia progression. Our conclusions are limited due to the OLE design and use of external controls and need to be confirmed in long-term trials."

Clinical • Journal • P2/3 data • Alzheimer's Disease • CNS Disorders • Dementia

Predicting Cognitive Decline Using Baseline Data in Cognitively Unimpaired Older Adults: Results from the A4 Trial (AAN 2025) - "These findings underscore the importance of baseline neuropsychological scores and plasma P-tau217 in predicting cognitive decline. Predictive models using these practical measures can improve clinical trial design and optimize participant selection, enhancing the effectiveness of interventions."

Clinical • Alzheimer's Disease • CNS Disorders

Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer's disease: an open label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU Trial. (PubMed, medRxiv) - P2/3 | "The randomised, placebo-controlled, double-blind, phase 2/3 multi-arm trial (DIAN-TU-001) assessed solanezumab or gantenerumab versus placebo in participants who were between 15 years before to 10 years after their estimated years to symptom onset and had a Clinical Dementia Rating (CDR) global score of 0 (cognitively normal) to 1 (mild dementia). Conclusions are limited due to the OLE design and use of external controls and need to be confirmed in long term trials. National Institutes on Aging, Alzheimer's Association, GHR, F. Hoffmann-La Roche, Ltd/Genentech."

Journal • P2/3 data • Alzheimer's Disease • CNS Disorders • Dementia