gantenerumab (RG1450) / Roche, Novartis - LARVOL DELTA

Estimating treatment effects in clinical studies of Alzheimer's disease: What are estimands and why do we need them? (PubMed, Alzheimers Dement) - "In Alzheimer's disease (AD), potential ICEs include additional AD medication use, discontinuation of treatment, and death. We describe estimands in recent clinical studies of anti-amyloid therapies, including gantenerumab, lecanemab, and donanemab, in AD and use the evoke and evoke+ studies of semaglutide in early-stage symptomatic AD as examples of estimand application in AD trials."

Journal • Review • Alzheimer's Disease • CNS Disorders

Gantenerumab for Early Alzheimer's Disease: An Updated Systematic Review and Meta-Analysis. (PubMed, Brain Behav) - "Gantenerumab significantly reduces amyloid and statistically improves select functional (FAQ) and cognitive (ADAS-Cog13) measures in early AD; however, these changes remain below accepted MCID thresholds, indicating a lack of true clinical meaningfulness. Combined with its failure to enhance global cognition and an increased ARIA risk, routine clinical use is not supported."

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

Volume change with gantenerumab: Impact of amyloid-related imaging abnormalities and amyloid removal. (PubMed, Alzheimers Dement) - P3 | "ARIA are not associated with long-term parenchymal reduction; rather, they are linked to a fluid shift from the external space to the ventricles. Amyloid removal correlates with parenchymal changes, but white matter changes suggest additional mechanisms beyond local clearance. Neither phenomenon was associated with worse clinical outcomes."

Clinical • Journal • Alzheimer's Disease • CNS Disorders

Pharmacological and Clinical Heterogeneity of Anti-Amyloid Monoclonal Antibodies in Early Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Trials. (PubMed, Med Sci (Basel)) - "PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for phase III placebo-controlled trials evaluating lecanemab, donanemab, aducanumab, and gantenerumab in patients with mild cognitive impairment due to AD or mild AD dementia with biomarker confirmation of amyloid pathology. The benefit-risk profile appears heterogeneous across individual antibodies and may reflect pharmacological differences in amyloid targeting and clearance mechanisms. These findings support cautious, individualized use of anti-amyloid therapies and highlight the need for longer-term studies to determine whether short-term slowing of decline translates into clinically meaningful disease modification."

Biomarker • Clinical • Heterogeneity • Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Hematological Disorders

Comparative risk of amyloid-related imaging abnormalities with anti-amyloid-β monoclonal antibodies: A systematic review and penalized likelihood network meta-analysis of randomized trials. (PubMed, J Alzheimers Dis) - "The highest ARIA-E risk was seen with donanemab and aducanumab, followed by gantenerumab and lecanemab. APOE ε4 carriage significantly elevated ARIA-E (OR 2.28) and ARIA-H (OR 2.07) risk, with a clear gene-dose effect in homozygotes.ConclusionsARIA risk varies substantially across anti-amyloid-β therapies and is strongly modulated by APOE ε4 status. These findings support genotype-informed risk stratification and individualized MRI monitoring to optimize the benefit-risk balance of disease-modifying therapies in AD."

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

Sex Differences In Treatment Response To Gantenerumab In Dominantly Inherited Alzheimer's Disease (AAIC 2026) - No abstract available

Alzheimer's Disease • CNS Disorders

Tau Pathology Interferes With Amyloid Removal By Gantenerumab (AAIC 2026) - No abstract available

Tau Pathology Interferes With Amyloid Removal By Gantenerumab (AAIC 2026) - No abstract available

Alzheimer's Disease • CNS Disorders

Understanding quantitative effects of anti-amyloid therapies on tau biomarkers and functional outcome. Insights from a comprehensive mechanistic quantitative systems pharmacology study. (PubMed, Front Pharmacol) - "We derived an antibody specific normalized decrease of plasma p-tau181 (-15% for donanemab, -45% for aducanumab and -75% for lecanemab) to determine trial duration for achieving central amyloid negativity. This provides a hypothesis for the impact of disease pathology and gender effect on functional outcomes with lecanemab and gantenerumab. With further validation, this model has the capability to support optimization of clinical trial design for amyloid-tau combination therapy."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders • Dementia • p-tau181

Functional connectome metrics reveal distinct prognostic subtypes in two Phase 3 gantenerumab trials. (PubMed, Alzheimers Dement (N Y)) - "rs-fMRI graph metrics might effectively stratify participants with AD in clinical trials and serve as potential prognostic biomarkers."

Journal • P3 data • Alzheimer's Disease • CNS Disorders

Efficacy of Gantenerumab Compared to Placebo in Adults with Alzheimer’s Disease: An Updated Systematic Review and Meta-analysis of Cognitive Function and Amyloid Plaque Reduction (AAN 2026) - "Although, a substantial increase in ARIA incidence counterbalances these benefits. Further long-term trials are needed to determine optimal use benefits from gantenerumab therapy."

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

Amyloid-beta-targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer's disease. (PubMed, Cochrane Database Syst Rev) - "The effect of amyloid-beta-targeting monoclonal antibodies on cognitive function and dementia severity at 18 months in people with mild cognitive impairment or mild dementia due to Alzheimer's disease is trivial, while on functional ability, it is small at best. Amyloid-beta-targeting monoclonal antibodies increase the risk of amyloid-related imaging abnormalities. Both desirable outcomes and adverse events were inconsistently reported in the studies included in the review. Successful removal of amyloid from the brain does not seem to be associated with clinically meaningful effects in people with mild cognitive impairment or mild dementia due to Alzheimer's disease. Future research on disease-modifying treatments for Alzheimer's disease should focus on other mechanisms of action."

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

EVALUATING DIFFUSION MRI AS A BIOMARKER OF TREATMENT RESPONSE IN AMYLOID-TARGETING ALZHEIMER'S DISEASE TRIALS (ADPD 2026) - "This study shows novel longitudinal findings that dMRI metrics are dynamically altered by amyloid-targeting therapies."

Biomarker • IO biomarker • Alzheimer's Disease • CNS Disorders • APOE

EXPLAINING AD PROGRESSION IN CLINICAL TRIALS USING A MULTI-MODAL PANEL OF BASELINE MEASUREMENTS (ADPD 2026) - P3 | "We assessed how much variability in the natural progression of Clinical Dementia Rating-Sum of Boxes (CDR-SB) can be explained by multimodal baseline measurements from clinical trials. A non-linear, mixed-effect disease progression model based on Richards' growth curve was applied to longitudinal CDR-SB data collected over 27 months from 761 participants in the placebo arms of the Phase III GRADUATE I&II (NCT03444870&NCT03443973) studies with gantenerumab in early symptomatic AD... A limited panel of baseline measurements can reduce variability in disease progression, improving the reliability of disease progression assessments in clinical trials, particularly useful in smaller, statistically underpowered studies. This approach provides a foundation for virtual placebo arms, potentially enabling smaller, shorter trials with greater confidence in quantifying disease progression."

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • Inflammation • p-tau181

EFFECTS OF ΑLPHA-SYNUCLEIN CO-PATHOLOGIES ON ALZHEIMER'S DISEASE PROGRESSION AND GANTENERUMAB EFFICACY IDENTIFIED BY CSF AND VOLUMETRIC MRI SIGNATURES (ADPD 2026) - P3 | "The association of a-Syn pathology with faster cognitive decline and diminished response to amyloid-targeting therapy gantenerumab suggests that a-Syn may play a critical role in the progression of AD."

Clinical • 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=438 | Active, not recruiting | Sponsor: Washington University School of Medicine | N=210 ➔ 438 | Trial primary completion date: Sep 2019 ➔ Sep 2023

Biomarker • Enrollment change • Trial primary completion date • 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=210 | Recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Dec 2016 ➔ Mar 2017

Biomarker • Trial completion date • 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=438 | Recruiting | Sponsor: Washington University School of Medicine | Active, not recruiting ➔ Recruiting

Biomarker • Enrollment open • 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 | Recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Jul 2022 ➔ Oct 2027 | Trial primary completion date: Jul 2022 ➔ Oct 2027

Biomarker • Trial completion date • Trial primary completion date • 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 | Recruiting | Sponsor: Washington University School of Medicine | Completed ➔ Recruiting | N=194 ➔ 490 | Trial completion date: Mar 2020 ➔ Jul 2022 | Trial primary completion date: Nov 2019 ➔ Jul 2022

Biomarker • Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • 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 | Recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Oct 2027 ➔ Jul 2028 | Trial primary completion date: Oct 2027 ➔ Apr 2028

Biomarker • Trial completion date • Trial primary completion date • 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=194 | Completed | Sponsor: Washington University School of Medicine | Recruiting ➔ Completed | N=490 ➔ 194 | Trial completion date: Mar 2021 ➔ Mar 2020 | Trial primary completion date: Dec 2020 ➔ Nov 2019

Biomarker • Enrollment change • Trial completion • Trial completion date • Trial primary completion date • 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

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=210 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting

Biomarker • Enrollment closed • 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=210 | Recruiting | Sponsor: Washington University School of Medicine | Not yet recruiting ➔ Recruiting

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