gantenerumab (RG1450) / Roche, Novartis - LARVOL DELTA

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

Efficacy and Safety of Gantenerumab in Patients With Alzheimer Disease: A Systematic Review and Meta-analysis. (PubMed, Clin Neuropharmacol) - "In conclusion, patients with Alzheimer disease treated with gantenerumab showed significant improvement in the ADAS score, FAQ score, hippocampal volume, and CSF biomarkers compared with those treated with placebo. However, the use of gantenerumab is associated with a higher incidence of ARIA-E and ARIA-H."

Journal • Retrospective data • 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

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

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

Blood-based pre-screening in the SKYLINE secondary prevention Ph3 gantenerumab study. (PubMed, Alzheimers Dement) - P3 | "We compared blood-based biomarker (BBBM) performance in SKYLINE and Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4). Pre-screening improved amyloid positivity (defined by positron emission tomography/cerebrospinal fluid) screen failure rate. Tau phosphorylated at threonine 181 (pTau181) and apolipoprotein E4 protein was the highest-performing combination among BBBMs tested. Pre-screening eased participant burden by reducing subsequent screening procedures."

Biomarker • Journal • Retrospective data • Alzheimer's Disease • CNS Disorders • APOE • p-tau181

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

Interpreting the evidence on gantenerumab for dominantly inherited Alzheimer's disease - Authors' reply. (PubMed, Lancet Neurol) - No abstract available

Journal • Alzheimer's Disease • CNS Disorders

Interpreting the evidence on gantenerumab for dominantly inherited Alzheimer's disease. (PubMed, Lancet Neurol) - No abstract available

Journal • Alzheimer's Disease • CNS Disorders

Interpreting the evidence on gantenerumab for dominantly inherited Alzheimer's disease. (PubMed, Lancet Neurol) - No abstract available

Journal • Alzheimer's Disease • CNS Disorders

Regional effects of gantenerumab on neuroimaging biomarkers in the DIAN-TU-001 trial. (PubMed, Alzheimers Dement) - "Gantenerumab unevenly decreased Aβ burden as measured by PiB-PET across brain regions. The strongest decrease in PiB-PET uptake was in basal ganglia and medial frontal structures. Variable drug effect on Aβ was partly due to the amount of burden present before treatment. There was no regional effect on FDG-PET metabolism or MRI volumetrics after 4 years."

Biomarker • Clinical • Journal • 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

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

Trends in Research on Gantenerumab for Alzheimer's Disease: A Bibliometric and Thematic Analysis. (PubMed, CNS Neurol Disord Drug Targets) - "GR-related literature showed sustained thematic focus, growing international collaboration, and a steady rise in publication volume within the field of AD. These findings highlight the continued need for clinical and biomarker-focused investigations to advance therapeutic development in AD."

Journal • Alzheimer's Disease • CNS Disorders

Japanese participant data from three gantenerumab trials in early Alzheimer's disease. (PubMed, Alzheimers Dement) - P3 | "Gantenerumab was evaluated in Japanese participants with Alzheimer's disease (AD) in two global phase 3 trials and a phase 2 trial in Japan. Relative reduction in Clinical Dementia Rating Sum of Boxes (CDR-SB) deterioration favored gantenerumab in Japanese-GRADUATE (42%) more than in global-GRADUATE (9%) and JP40959 (-24%). Amyloid reduction in Japanese-GRADUATE was greater than in global-GRADUATE and JP40959. Overall, 72.7% and 27.5% of Japanese- and global-GRADUATE, respectively, achieved an amyloid-negative status. Cognitive and functional decline, and amyloid reduction could be related to baseline body weight and disease severity."

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

Lecanemab preferentially binds to smaller aggregates present at early Alzheimer's disease. (PubMed, Alzheimers Dement) - "Anti amyloid beta therapeutics are compared by their diffusible aggregate binding characteristics. In-vitro and brain-derived aggregates are tested using single-molecule detection. Lecanemab shows therapeutic success by binding to aggregates formed in early disease. Lecanemab binds to these aggregates with high affinity and coats them better."

Journal • Alzheimer's Disease • CNS Disorders

DISCOVERY BLOOD-BASED BIOMARKERS FOR THE DETECTION AND MONITORING OF AMYLOID RELATED IMAGING ABNORMALITIES (ARIA) (ADPD 2025) - "Methods We assembled one of the largest and best characterized sets of plasma samples from a total of 4 Phase III randomized clinical trials of gantenerumab including participants that had ARIA-E on at least one MRI scan and participants without ARIA-E...We identified biomarkers that become abnormal during ARIA-E. However, these biomarkers require further investigations to support their utility in clinical routine."

Biomarker

IMPACT OF ARIA AND AMYLOID REMOVAL ON CEREBRAL VOLUME CHANGES WITH GANTENERUMAB (ADPD 2025) - "The relationship between amyloid removal and brain volume loss varied between regions typically affected by tau pathology and those that are not. Further analyses are ongoing to better characterize these findings."

BRAIN SHUTTLES TO NOVEL RECEPTORS TO OVERCOME LIABILITIES OF FIRST -GENERATION SHUTTLED ANTI-AMYLOID THERAPEUTICS (ADPD 2025) - "For example, Roche's trontinemab uses a shuttle to Transferrin Receptor ( TfR) to enhance PK and plaque clearance while reducing ARIA of the anti -amyloid beta (anti -Aβ) antibody gantenerumab. Our work demonstrates that liabilities of TfR shuttles can be improved by engaging novel targets on the BBB and further advances a potential shuttle for clinical development that could improve upon the profile of existing TfR -Abeta mAbs such a s trontinemab."

Hematological Disorders • TFRC

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