gantenerumab (RG1450) / Roche, Novartis - LARVOL DELTA

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

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 | 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=438 | 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 | Trial primary completion date: Jan 2017 ➔ Sep 2019

Biomarker • 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

Biomarker • New P2/3 trial • 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 | Trial completion date: Dec 2023 ➔ Mar 2021 | Trial primary completion date: Sep 2023 ➔ Dec 2020

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=210 | Recruiting | Sponsor: Washington University School of Medicine | Trial primary completion date: Jul 2014 ➔ Jan 2017

Biomarker • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

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) - "Gantenerumab demonstrates modest benefits in functional outcomes. 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

Bioequivalence Between a Gantenerumab Disposable Syringe and an Autoinjector: A Randomized Controlled Trial in Healthy Volunteers. (PubMed, Clin Pharmacol Drug Dev) - "BE between AI and DS SC administration was demonstrated with geometric LS mean ratios (90% CIs) for Cmax, AUC0-inf, and AUC0-last of 1.078 (1.006, 1.155), 1.053 (0.986, 1.124), and 1.054 (0.992, 1.121), respectively, all within the 0.80-1.25 BE range. Safety findings were consistent with the known safety profile of gantenerumab."

Clinical • Journal • Alzheimer's Disease • CNS Disorders

Biomarkers. (PubMed, Alzheimers Dement) - "Our preliminary findings indicated that ARIA-E is associated with longitudinal PiB-PET decrease and Aβ AF, supporting the link between ARIA-E, changes in PiB-PET, and local Aβ removal observed at autopsy."

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

Biomarkers. (PubMed, Alzheimers Dement) - "The disappearance (resolution) of ARIA-H microhemorrhages is relevant to the management and continued dosing of patients receiving anti-amyloid immunotherapies as this is guided by the presence of ARIA (including cumulative treatment emergent microhemorrhages) as well as clinical symptoms. A microhemorrhage number alone may not be indicative of the potentially dynamic nature of ARIA-H."

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

Biomarkers. (PubMed, Alzheimers Dement) - "Our findings suggest neuroinflammation's role in ARIA-E progression and demonstrate the potential of g-DBSI to detect microstructural changes before the onset of ARIA-E. This pilot study supports g-DBSI as a noninvasive imaging tool to monitor ARIA progression, providing insights into neuroinflammation and vasogenic edema. Further research with larger cohorts is necessary to further delineate and validate the potential clinical utility of g-DBSI."

Biomarker • Journal • Hematological Disorders • Inflammation

Drug Development. (PubMed, Alzheimers Dement) - "Patients undergoing anti-amyloid therapy are at risk of developing ARIAs, particularly those carrying the ApoE4 genotype. ARIAs are generally asymptomatic, do not necessitate treatment discontinuation, and show differing courses depending on the subtype: ARIA-E resolves spontaneously, while ARIA-H persists. Aducanumab was associated with the highest frequency of ARIA events. These findings underscore the importance of regular MRI monitoring and patient-specific management strategies to mitigate complications and optimize therapy outcomes."

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