gosuranemab (BIIB092) / Biogen, BMS - LARVOL DELTA

THE PERFORMANCE OF CSF NPTX2 AS A BIOMARKER OF CLINICAL PROGRESSION IN ALZHEIMER'S DISEASE (ADPD 2025) - P2 | " TANGO (NCT03352557) was a Phase 2 clinical study assessing the safety and efficacy of gosuranemab, an anti -tau monoclonal antibody, in participants with early AD... These preliminary results suggest CSF NPTX2 may be a useful biomarker for predicting cognitive decline in AD. Future analysis of CSF NPTX2 in amyloid positive MCI and mild AD subsets and its relationship with known biomarkers of AD (tau, phosphorylated tau, amyloid beta) will be explored to understand how this marker can be applied to early disease staging and monitoring of clinical progression."

Biomarker • Clinical • Alzheimer's Disease • CNS Disorders

MEASUREMENT OF CSF MTBR-TAU243 IN CLINICAL TRIALS OF ALZHEIMER'S DISEASE AND PROGRESSIVE SUPRANUCLEAR PALSY (ADPD 2025) - P1, P2 | "Methods CSF was serially collected as a sub-study of the following placebo-controlled clinical trials using an anti-tau monoclonal antibody (gosuranemab): TANGO (NCT03352557), a Phase 2 study in early AD; PASSPORT (NCT03068468), a Phase 2 study in PSP; and CN002001 (NCT02294851), a Phase 1 study in HV...Conclusions By exploring the relationship between clinical outcomes and CSF MTBR-tau243, these studies will elucidate the potential role of CSF MTBR-tau243 as a biomarker in tauopathies. The inclusion of HV CSF collected during a tau-targeting study will provide understanding of the disease-specific role of MTBR-tau243 as a treatment response biomarker."

Clinical • Alzheimer's Disease • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy • CSF T-tau

Comparative the efficacy and safety of Gosuranemab, Semorinemab, Tilavonemab, and Zagotenemab in patients with Alzheimer's disease: a systematic review and network meta-analysis of randomized controlled trials. (PubMed, Front Aging Neurosci) - "Further studies are needed to confirm these findings, assess long-term effects, and refine treatment protocols. https://www.crd.york.ac.uk/prospero/#myprospero, CRD42024583388."

Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Dementia • Infectious Disease • Nephrology

Developing Topics. (PubMed, Alzheimers Dement) - "The correlations of plasma p-tau217 with amyloid and tau PET at baseline suggest a relationship with both underlying pathological hallmarks of AD. Similar to results from observational cohorts, correlation of baseline plasma p-tau217 and clinical decline observed during the TANGO trial supports the utility of plasma p-tau217 as a potential prognostic biomarker of disease. Data from additional studies are needed to define appropriate use cases and relevant thresholds for plasma p-tau217 as a biomarker of disease pathology that can be used to prescreen patients in clinical trials."

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

Synthetic receptors for programmable tau-responsive cellular therapies (Neuroscience 2024) - "Receptors with recognition domains derived from clinical anti-tau mAbs (semorinemab, gosuranemab, bepranemab) were built and expressed in mouse mesenchymal stromal cells (mMSCs) (Fig 1A; synNotch constructs displayed). We envision tau receptors being used in a cell-based therapy, outfitting microglia and astrocytes with novel therapeutic behaviors. In neurons, tau receptors may serve as useful tools for reporting the extent of local tau pathology in real-time."

Alzheimer's Disease • CNS Disorders • Dementia • BDNF

Assessment of Baseline Plasma p-tau217 in TANGO, a Randomized, Placebo-controlled Phase 2 Study of Gosuramemab in Patients with Early Alzheimer’s Disease (AAIC 2024) - "Background: TANGO was a Phase 2 clinical study designed to assess the safety and efficacy of gosuranemab, an anti-tau monoclonal antibody, in participants with mild cognitive impairment due to Alzheimer’s disease (AD) or with mild AD dementia... The correlations of plasma p-tau217 with amyloid and tau PET at baseline suggest a relationship with both underlying pathological hallmarks of AD. Similar to results from observational cohorts, correlation of baseline plasma p-tau217 and clinical decline observed during the TANGO trial supports the utility of plasma p-tau217 as a potential prognostic biomarker of disease. Data from additional studies are needed to define appropriate use cases and relevant thresholds for plasma p-tau217 as a biomarker of disease pathology that can be used to prescreen patients in clinical trials."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • p-tau181

EXPLORATORY EVALUATION OF TAU PET POSITIVITY OR BRAAK STAGING AND CLINICAL PROGRESSION IN TANGO PHASE 2 CLINICAL TRIAL OF GOSURANEMAB. (ADPD 2024) - "These exploratory analyses suggest that assessment of [18F]MK-6240 tau positivity using visual read or quantitative thresholds is feasible for implementation in clinical trials. Tau positive participants by visual read accumulated more tau and clinically progressed more over 18 months than tau negative participants. Quantitative Braak staging identified the participants with the greatest magnitude of clinical progression."

Clinical • P2 data • Tau PET • Alzheimer's Disease • CNS Disorders

DISTRIBUTION OF ALPHA-SYNUCLEIN CO-PATHOLOGY IN MCI, MILD ALZHEIMER'S DISEASE, AND PROGRESSIVE SUPRANUCLEAR PALSY CLINICAL TRIAL COHORTS (ADPD 2024) - P2 | "The results suggest that roughly one third of the MCI and mild AD Phase 2 gosuranemab clinical trial participants have the presence of αS pathology with lower positivity observed in PSP. Ongoing analyses focus on elucidating the interplay between the presence αS pathology and its influence on clinical progression and response to emerging therapies."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Lewy Body Disease • Movement Disorders • Multiple System Atrophy • Progressive Supranuclear Palsy

TANGO: a placebo-controlled randomized phase 2 study of efficacy and safety of the anti-tau monoclonal antibody gosuranemab in early Alzheimer's disease. (PubMed, Nat Aging) - P2 | "No significant effects were identified in cognitive and functional tests as no dose resulted in a favorable change from the baseline CDR-SB score at week 78 compared to placebo control (adjusted mean change: placebo, 1.85; low dose, 2.20; intermediate dose, 2.24; high dose, 1.85). At week 76, all doses caused significant (P < 0.0001) reductions in the cerebrospinal fluid levels of unbound N-terminal tau compared to placebo."

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

Analysis of clinical failure of anti-tau and anti-synuclein antibodies in neurodegeneration using a quantitative systems pharmacology model. (PubMed, Sci Rep) - "Integration with a physiologically based pharmacokinetic (PBPK) model allowed us to simulate clinical trials of anti-tau antibodies gosuranemab, tilavonemab, semorinemab, and anti-aSyn antibodies cinpanemab and prasineuzumab. The study generates optimal values of selectivity, sensitivity and PK profiles for antibodies. The study identifies a gradient of decreasing target engagement from CSF to the synaptic cleft as a key driver of efficacy, quantitatively identifies various improvements for drug design and emphasizes the need for QSP modelling to support the development of tau and aSyn antibodies."

Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

Passive tau-based immunotherapy for tauopathies. (PubMed, Handb Clin Neurol) - "At present, 12 anti-tau antibodies have entered clinical trials, and 7 of them are still in clinical testing for primary tauopathies and AD (semorinemab, bepranemab, E2814, JNJ-63733657, Lu AF87908, PNT00, and APNmAb005). Two other anti-tau monoclonal antibodies have been discontinued for the treatment of primary tauopathies, i.e., gosuranemab and tilavonemab. Further evidence will come from ongoing Phase I/II trials on passive immunotherapeutics for treating primary and secondary tauopathies."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Frontotemporal Lobar Degeneration • Movement Disorders • Progressive Supranuclear Palsy

MODELING PHARMACODYNAMIC EFFECTS OF PUBLISHED CLINICALLY TESTED ANTI-TAU AND ANTISYNUCLEIN ANTIBODIES TO IMPROVE CLINICAL TRIAL DESIGN (ADPD 2023) - "We si mulated clinical trials of gosuranemab, tilavonemab, semorinemab, cinpanemab and prasinezumab using published clinical profiles. The current model suggests that the antibodies' effect on accessible biomarkers in CSF is quite different from changes in other brain compa rtments, notably in the synaptic cleft and neuronal uptake which are proxies for disease progression."

Clinical • PK/PD data • Immunology

Exploratory evaluation of 18F-MK-6240 tau PET positivity in TANGO phase 2 clinical trial of gosuranemab (BIIB092) in Mild Cognitive Impairment and mild Alzheimer’s disease (AAIC 2022) - No abstract available

Clinical • P2 data • Tau PET • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

ASSESSMENT OF PLASMA P-TAU181 IN TANGO, A PHASE 2 STUDY OF GOSURAMEMAB IN PATIENTS WITH EARLY ALZHEIMER’S DISEASE. (CTAD 2022) - "Background : Gosuranemab is a humanized monoclonal antibody that binds to the N-terminus of tau with high affinity... Plasma p-tau181 data from the TANGO study will help inform our understanding of plasma biomarkers in AD, and the utility of this marker as a tool for patient selection and as a biomarker of disease progression. The correlations of plasma p-tau181 with amyloid and tau PET at baseline suggests a relationship with the underlying pathological hallmarks of AD. Furthermore, the correlation of baseline plasma p-tau181 and clinical decline observed over the course of the TANGO trial supports the utility of plasma p-tau181 as a potential prognostic biomarker of disease."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Taurine depletion during fetal and postnatal development blunts firing responses of neocortical layer II/III pyramidal neurons. (PubMed, Front Mol Neurosci) - "Here we examined the effects of fetal and infantile taurine depletion caused by knockout of the taurine transporter Slc6a6 on firing properties of layer II/III pyramidal neurons in the mouse somatosensory cortex at 3 weeks of postnatal age, using the whole-cell patch-clamp technique...This was due to much lower membrane voltage levels during interspike intervals in knockout neurons, promoting greater recovery of voltage-gated Na channels from inactivation. Thus, taurine depletion in pyramidal neurons blunted neuronal responses to external stimuli through increasing the stability of repetitive firing, presumably mediated by larger increases in membrane K conductance during interspike intervals."

Journal • SLC6A6

PBPK-PD modeling for the preclinical development and clinical translation of tau antibodies for Alzheimer's disease. (PubMed, Front Pharmacol) - "Model validation for humans was performed using publicly available clinical data for gosuranemab. In-silico analyses were performed to predict tau engagement in human brain for a range of tau antibody affinities and various dosing regimens. PBPK-PD modeling enabled a quantitative understanding for the relationship between dose, affinity, and target engagement, which supported lead candidate optimization and predictions of clinically efficacious dosing regimens."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders

Drug delivery of memantine with carbon dots for Alzheimer's disease: blood-brain barrier penetration and inhibition of tau aggregation. (PubMed, J Colloid Interface Sci) - "The kinetics and magnitude of tau aggregation were measured in the presence of CDs, which demonstrates that both B-CDs-MH and B-CDs alone are the most effective inhibitors of tau aggregation with IC values of 1.5 ± 0.3 and 1.6 ± 1.5 μg/mL, respectively. Taken together, our findings hold therapeutic significance to enhance the efficient delivery of MH to target AD pathology in the brain for improved efficacy."

Journal • Alzheimer's Disease • CNS Disorders

Top-line results from TANGO, a Phase 2 study of gosuranemab in participants with mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease (CTAD 2021) - P2 | "Targeting extracellular N-terminal tau with gosuranemab did not result in clinical benefit in participants with MCI due to AD or mild AD. Based on lack of efficacy in the placebo-controlled period, the TANGO long-term extension study has been terminated, and the clinical development of gosuranemab in AD has been discontinued."

Late-breaking abstract • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Tau PET

Biogen Announces Late Breakers and Additional New Data Presentations at the 2021 Clinical Trials on Alzheimer’s Disease (CTAD) Meeting (GlobeNewswire) - “Biogen Inc…announced the company will present a variety of new data from its Alzheimer’s disease product portfolio and clinical development pipeline at the upcoming annual Clinical Trials on Alzheimer’s Disease conference (CTAD), held November 9-12 virtually and in Boston, Massachusetts…A late breaking presentation will highlight important new data from over 7,000 plasma samples from the ADUHELM Phase 3 trials that, for the first time, examines the effect of ADUHELM on plasma phosphorylated tau181 (p-Tau181) and its correlation to amyloid beta plaques and disease progression, as measured by clinical decline endpoints, in patients with early Alzheimer’s disease.”

Late-breaking abstract • P1 data • P2 data • P3 data • Alzheimer's Disease • CNS Disorders • Frontotemporal Lobar Degeneration

TANGO: Phase 2 Study of BIIB092 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2; N=654; Terminated; Sponsor: Biogen; Active, not recruiting ➔ Terminated; The study (NCT03352557) was terminated based on lack of efficacy following the placebo-controlled period readout.

Clinical • Trial termination • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APOE

TANGO: Phase 2 Study of BIIB092 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2; N=654; Active, not recruiting; Sponsor: Biogen; Trial completion date: Mar 2024 ➔ Aug 2021; Trial primary completion date: Mar 2024 ➔ Aug 2021

Clinical • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APOE

Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial. (PubMed, Nat Med) - P2 | "Incidences of adverse events and deaths were similar between groups. This well-powered study suggests that N-terminal tau neutralization does not translate into clinical efficacy."

Clinical • Journal • P2 data • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

Antisense Therapy Stifles CSF Tau in Mild Alzheimer’s Disease (Alzforum) - "'Additional biomarker data, including for downstream neurodegenerative biomarkers such as NfL, and clinical data will be needed to clarify the treatment's disease-slowing effects,' he wrote to Alzforum (full comment below)."

Media quote • Alzheimer's Disease • Tauopathies And Synucleinopathies

[VIRTUAL] A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Parallel Cohort Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy Study of Intravenously Infused BIIB092 in Patients with Four Different Primary Tauopathy Syndromes (AAIC 2021) - "Six months of BIIB092 treatment was well tolerated and appears to bind to the N-terminal epitopes in individuals with four different tauopathy syndromes."

Clinical • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders • Frontotemporal Lobar Degeneration • Immunology • Movement Disorders • Progressive Supranuclear Palsy • MRI

[VIRTUAL] Baseline biomarker (Tau PET) characteristics from Tango: A phase 2 trial of gosuranemab (BIIB092) in early Alzheimer's disease (AAIC 2021) - "Cross-sectionally, higher tau PET SUVR was associated with increasing disease severity and worse clinical scores, as expected. The TANGO Tau PET sub-study will aid our understanding of gosuranemab’s effect on tau pathology and further inform on the value of tau PET in clinical trials."

Biomarker • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Amyloid PET • Tau PET