solanezumab (LY2062430) / Eli Lilly - LARVOL DELTA

DECODING HETEROGENEITY IN A4: EXPLAINABLE ML FINDS SOLANEZUMAB RESPONSIVE SUBGROUPS IN (ADPD 2026) - "An explainable ML strategy identified clinically interpretable profiles that may be preferential responders to solanezumab, despite the overall negative A4 result. These exploratory findings, based on limited sample sizes, suggest that greater regional brain volume and stronger psychomotor speed/attention at baseline may enrich for treatment benefit. Independent replication, presentation of absolute subgroup counts, and adjustment for multiplicity are warranted; if confirmed, this approach could support precision enrichment in future preclinical AD trials."

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

EFFICACY AND SAFETY OF IMMUNOTHERAPIES FOR ALZHEIMER'S DISEASE: A NETWORK META-ANALYSIS (ADPD 2026) - "The results found that monoclonal antibodies such as aducanumab and solanezumab consistently ranked higher in terms of Surface Under the Cumulative Ranking (SUCRA) score. However, this contrasts with the outlier of shorter-term treatments as AN-1792 with QS-21, a vaccine, is found to be the better treatment option. For heightened comprehension on the efficacy and safety choice of immunotherapies, future wellconducted and designed large studies encompassing specific safety outcomes, financial analysis is highly recommended. Also, as monoclonal antibodies are seen as demonstrating a higher efficacy, it is imperative for more focus driven towards further increasing the safety of these specific types of immunotherapies in the future."

Retrospective data • Alzheimer's Disease • CNS Disorders

TIME TO REGIONAL TAU POSITIVITY – A NOVEL APPROACH FOR ASSESSING LONGITUDINAL TAU ACCUMULATION AND TREATMENT RESPONSE (ADPD 2026) - P2/3, P3 | "The T2RT+ was defined as an event for each composite and analyzed using Kaplan-Meier (KM) estimates for solanezumab and placebo groups... The T2RT+ approach captures the tau staging patterns in preclinical AD cohorts and might serve as a clinically meaningful, complementary endpoint to conventional SUVR approach for assessing treatment efficacy. Additional analyses exploring the baseline characteristics associated with progression to tau-PET positivity will be presented at the conference."

Alzheimer's Disease • CNS Disorders

Drug Development. (PubMed, Alzheimers Dement) - "Using epidemiologic and econometric methods to analyze individual-level data from trials of amyloid-targeting drugs will improve our understanding of amyloid as a surrogate outcome for cognition. In this instance, results are imprecise because solanezumab did not effectively remove amyloid. However, reproducing these analyses using individual-level data from effective anti-amyloid trials has the potential to shape treatment strategies and inform use of surrogate outcomes in future approval processes."

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

Drug Development. (PubMed, Alzheimers Dement) - "Despite solanezumab worsening biomarkers levels, the data suggests that solanezumab has a limited efficacy to improve the cognitive function of participants with early AD."

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

Biomarkers. (PubMed, Alzheimers Dement) - P3 | "Although CDR0.5 subgroup participants demonstrated higher mean FTP regional SUVR values compared with CDR0 participants, the baseline tau PET patterns in TRAILBLAZER-ALZ 3 are similar to other preclinical AD populations, even for participants in the CDR0.5 subgroup. Average regional baseline SUVR values support prior findings that tau deposition occurs sequentially from the medial temporal, lateral temporal, parietal, and frontal lobes. Additional regional analyses will be presented."

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

Drug Development. (PubMed, Alzheimers Dement) - "Baseline tau PET was the strongest predictor of PACC decline. Using baseline-predicted PACC decline as APC can enhance treatment effect estimates and trial efficiency in preclinical AD."

Journal • Alzheimer's Disease • CNS Disorders • APOE

Developing Topics. (PubMed, Alzheimers Dement) - "The minimal differences between treatment and placebo-relative to the wide scoring scales-suggest that targeting amyloid plaques may be insufficient as a disease-modifying approach. These findings underscore the urgent need for alternative strategies. One such approach is NA-831, Biomed's novel small-molecule therapy based on neurogenesis and neuroprotection. Unlike amyloid-targeted antibodies, NA-831 aims to restore neuronal function and cognition by stimulating endogenous brain repair mechanisms. These emerging strategies may better align with the complex pathophysiology of AD and represent a promising new frontier in treatment."

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

Alzheimer's Imaging Consortium. (PubMed, Alzheimers Dement) - P3 | "Although CDR0.5 subgroup participants demonstrated higher mean FTP regional SUVR values compared with CDR0 participants, the baseline tau PET patterns in TRAILBLAZER-ALZ 3 are similar to other preclinical AD populations, even for participants in the CDR0.5 subgroup. Average regional baseline SUVR values support prior findings that tau deposition occurs sequentially from the medial temporal, lateral temporal, parietal, and frontal lobes. Additional regional analyses will be presented."

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

Alzheimer's Imaging Consortium. (PubMed, Alzheimers Dement) - "Using epidemiologic and econometric methods to analyze individual-level data from trials of amyloid-targeting drugs will improve our understanding of amyloid as a surrogate outcome for cognition. In this instance, results are imprecise because solanezumab did not effectively remove amyloid. However, reproducing these analyses using individual-level data from effective anti-amyloid trials has the potential to shape treatment strategies and inform use of surrogate outcomes in future approval processes."

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

Basic Science and Pathogenesis. (PubMed, Alzheimers Dement) - "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."

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

Developing Topics. (PubMed, Alzheimers Dement) - "The analysis shows striking divergent classes, with p -tau217 levels and amyloid PET CL values emerging as strong group-level predictors of class membership. However, neither biomarker is an accurate individual-level classifier of latent class. This analysis suggests that more sensitive cognitive measures or longer follow-up will be needed to detect a therapeutic benefit on cognition for most individuals, and supportive biomarker evidence will be essential for regulatory approval."

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

Post hoc data-driven subgroup analysis of the A4 Study: spatiotemporal atrophy predicts differential treatment response to solanezumab (CTAD 2025) - No abstract available

Retrospective data

Tau-Predictive Functional Connectome Patterns Predict Clinical Progression and Solanezumab Response in Preclinical Alzheimer's Disease (CTAD 2025) - No abstract available

Preclinical • Alzheimer's Disease • CNS Disorders

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