Tau positron emission tomography results from TOGETHER, a double‐blind, placebo‐controlled Phase II study of bepranemab in prodromal–mild Alzheimer’s disease
Bibliographic record
Abstract
BACKGROUND: Bepranemab is a recombinant, humanized, full-length immunoglobulin G4 monoclonal antibody that targets a mid-region epitope of human tau. TOGETHER (NCT04867616), a Phase II participant- and investigator-blinded, randomized, placebo-controlled study, assessed efficacy and safety of bepranemab in people with prodromal-mild Alzheimer's disease (AD). Previously presented data from TOGETHER indicate a clinical benefit with bepranemab. Here, we describe the effect of bepranemab on tau accumulation in the brain in study participants with prodromal or mild AD. METHODS: F] Genentech tau probe 1 (GTP1) and underwent positron emission tomography (PET) imaging at Baseline, Week 56, and Week 80. Eligibility criteria included prodromal-mild AD (National Institute on Aging and the Alzheimer's Association 2018 Stage 3/4); cerebral amyloid beta presence (PET or cerebrospinal fluid); global Clinical Dementia Rating (CDR) score of 0.5; CDR-Memory Box score ≥0.5. Secondary objectives included investigating the effect of bepranemab on tau-PET imaging at Weeks 56 and 80. PET images were analyzed by a central imaging laboratory to determine the standardized uptake value ratio relative to cerebellum in multiple brain regions. RESULTS: In total, 466 participants were randomized 1:1:1 across three arms (90 mg/kg bepranemab, 45 mg/kg bepranemab, placebo). Bepranemab slowed tau accumulation (by 33-58% vs placebo, across both bepranemab arms) in the whole cortical gray (n=scanned/total: 90 mg/kg bepranemab [n=113/152], 45 mg/kg bepranemab [n=104/152], and placebo [n=97/156]) and jack temporal meta regions (n=scanned/total: 90 mg/kg bepranemab [n=114/152], 45 mg/kg bepranemab [n=105/152], and placebo [n=97/156]) at Week 80 in the initial analysis of the full trial population (those who received at least a partial dose of study medication and had at least one valid post-Baseline clinic visit and efficacy assessment). Data on tau accumulation in regions based on Braak staging will be presented. CONCLUSION: TOGETHER provides the first clinical demonstration of slowing of tau accumulation with an antibody targeting the tau mid-region, as evidenced by tau PET imaging, and marks the first time that any tau-directed therapy has demonstrated a clinical benefit.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".