trontinemab (RG6102) / Roche, Royalty - LARVOL DELTA

PrevenTRON: A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P3 | N=1600 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders

Surrey and Borders Partnership NHS Foundation Trust has become the first site in Europe to join an international trial for a prospective Alzheimer's drug (The Independent) - "The trial will recruit 1,600 healthy adults aged between 55 and 80 to test whether the drug Trontinemab can delay or prevent the onset of Alzheimer's disease. UK participants will be screened for memory loss and given a blood test to check for the p-tau217 biomarker before receiving the treatment. Developed by Roche, Trontinemab is delivered intravenously and targets harmful amyloid plaques that damage brain cell function."

New trial • Alzheimer's Disease

Brain delivery and distribution of the novel Brainshuttle™ Aβ-targeting antibody trontinemab in participants with Alzheimer's disease measured with ⁸⁹Zr positron emission tomography (CTAD 2026) - No abstract available

Alzheimer's Disease • CNS Disorders

PrevenTRON: Evaluating the effect of trontinemab in cognitively unimpaired individuals with biomarkers of Alzheimer's disease at high risk of clinical decline (CTAD 2026) - No abstract available

Biomarker • Clinical • Alzheimer's Disease • CNS Disorders

Advanced imaging results from the Brainshuttle™ AD study with trontinemab in Alzheimer's disease (CTAD 2026) - No abstract available

Metastases • Alzheimer's Disease • CNS Disorders

Trontinemab in Alzheimer's disease – novel pharmacodynamic insights from the ongoing Phase Ib/IIa Brainshuttle™ AD study (CTAD 2026) - No abstract available

P1/2 data • PK/PD data • Alzheimer's Disease • CNS Disorders

SYMPOSIUM 1: Visualizing the Brainshuttle™: Pioneering neuroimaging and mechanistic insights of amyloid clearance with trontinemab (CTAD 2026) - No abstract available

PrevenTRON: A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P3 | N=1600 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P3 trial • Alzheimer's Disease • CNS Disorders

PrevenTRON Trial Design (NeurologyLive) - "PrevenTRON is a randomized, multicenter, double-blind, placebo-controlled phase 3 study targeting approximately 1,600 cognitively unimpaired participants at high risk of progression to symptomatic AD...The dosing regimen follows a two-phase approach. During a 24-week induction phase, participants receive trontinemab 7 times at 3.6 mg/kg every 4 weeks, intended to achieve rapid and robust amyloid clearance. This is followed by a lower-frequency maintenance phase designed to sustain amyloid control while reducing participant burden. The primary endpoint is time to clinical progression, defined as a confirmed Clinical Dementia Rating-Global Score greater than 0. Secondary endpoints include the Cognitive Function Instrument, Logical Memory, activities of daily living measures, and longitudinal amyloid PET in a subset of participants."

Clinical protocol • New P3 trial • Alzheimer's Disease

BRAINSHUTTLE Phase 1/2 Data (NeurologyLive) - "In the 3.6 mg/kg cohort, trontinemab reduced amyloid levels below the 24-centiloid positivity threshold in 91% of participants (n = 49/54) after 28 weeks of treatment; 72% (n = 39/54) achieved deep clearance below 11 centiloids. These reductions were accompanied by early and significant changes in CSF and plasma biomarkers of AD pathology, including total tau, phosphorylated tau 181, phosphorylated tau 217, and neurogranin....Amyloid-related imaging abnormalities with edema (ARIA-E) continued to be observed in fewer than 5% of participants across the 1.8 and 3.6 mg/kg dose cohorts combined (n = 4/149), with blinded data confirming this rate across the expanded program. This ARIA-E rate is substantially lower than what has been observed with the approved anti-amyloid antibodies: 13% for lecanemab and 24% for donanemab, a profile the investigators have cited as a potential differentiating advantage for trontinemab."

P1/2 data • Alzheimer's Disease

Roche presents new data in Alzheimer’s disease from across its integrated pharmaceutical and diagnostics portfolio at AAIC (Roche Press Release) - "A 90-minute Featured Research Session will showcase five oral presentations focused on the latest progress in the development of trontinemab, an investigational Brainshuttle bispecific 2+1 amyloid-beta targeting monoclonal antibody. Presenters will share new long-term safety, amyloid removal and biomarker data from the Phase Ib/IIa Brainshuttle AD open-label extension study. Modelling from this study has informed the dosing regimen for the ongoing Phase III TRONTIER 1 and 2 studies in early symptomatic Alzheimer’s disease...For the first time, Roche will also share the design of PrevenTRON, a Phase III study investigating trontinemab in preclinical Alzheimer’s disease...Emerging preclinical and clinical data on the immunomodulatory effects of NLRP3 inhibition in neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease will also be presented....In addition, new data will be presented for the approved Elecsys pTau181..."

Clinical protocol • Diagnostic • New P3 trial • P1/2 data • P3 data • Preclinical • Alzheimer's Disease • Parkinson's Disease

TRONTIER 1: A Study of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P3 | N=800 | Recruiting | Sponsor: Hoffmann-La Roche | -> Recruiting | Initiation date: Jan 2026 ➔ Sep 2025

Enrollment open • Trial initiation date • Alzheimer's Disease • CNS Disorders • Dementia

3-21-FRS-B: Featured Research Sessions - Shuttling past the barrier: From Brainshuttle(TM) AD long-term trontinemab data to secondary prevention of AD in PrevenTRON (AAIC 2026) - No abstract available

Evidence Supporting Preclinical AD As An Optimal Stage For Intervention With Trontinemab (AAIC 2026) - No abstract available

Preclinical

Simulation of amyloid clearance in Phase III studies with trontinemab in early symptomatic Alzheimer's disease (AAIC 2026) - No abstract available

P3 data • Alzheimer's Disease • CNS Disorders

PrevenTRON: Rationale and design of a Phase III trial of trontinemab in cognitively unimpaired individuals with biomarkers of Alzheimer's disease at high risk of clinical decline (AAIC 2026) - No abstract available

Biomarker • Clinical • P3 data • Alzheimer's Disease • CNS Disorders

Interim Long-term Biomarker Results From The Trontinemab Open-label Extension Of The Phase Ib/IIa Brainshuttle™ AD Study (AAIC 2026) - No abstract available

Biomarker • Clinical • P1/2 data

Long-term safety and amyloid removal with trontinemab: Interim data from the open-label extension of the Phase Ib/IIa Brainshuttle™ AD study (AAIC 2026) - No abstract available

Clinical • P1/2 data

Evaluating emerging amyloid-β centric drugs for the treatment of Alzheimer's disease. (PubMed, Expert Opin Emerg Drugs) - "The recent approvals of lecanemab and donanemab offered the first convincing evidence that reducing Aβ burden can modestly slow cognitive decline in early AD. Beyond these first-generation monoclonal antibodies, the pipeline includes next-generation antibodies with enhanced brain penetration (trontinemab), therapies designed also for presymptomatic intervention (remternetug tested for secondary prevention), and novel approaches targeting galectin-3 to disrupt Aβ aggregation and neuroinflammation. Active immunotherapies like UB-311 and small molecules such as ALZ-801, avoiding amyloid-related imaging abnormalities (ARIA), broaden the therapeutic horizon with potentially safer and more accessible options, but with no proven efficacy...Regulators have begun to restrict approval to genetically defined subgroups according to apolipoprotein E genotype, underscoring the need for precision medicine. Therefore, while Aβ-centric therapies are incremental, they represent essential..."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • APOE

BP42155: Brainshuttle AD: A Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7126209 Following Intravenous Infusion in Participants With Prodromal or Mild to Moderate Alzheimer's Disease (clinicaltrials.gov) - P1/2 | N=241 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2030 ➔ Jul 2027 | Trial primary completion date: Jun 2030 ➔ Jul 2027

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

Transport pathways across the blood-brain barrier for waste clearance and drug delivery. (PubMed, Fluids Barriers CNS) - "Here, we include lecanemab, trontinemab, dual TfR/CD98hc shuttles, evolocumab and alirocumab, immunoliposomes and other nanoparticles targeting TfR1 or LRP1. We will further highlight approaches which differ from these common ideas and demonstrate the current state of the art regarding drug delivery and waste clearance across the BBB."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dyslipidemia • LRP1 • SLC3A2 • SLC7A5 • TFRC

DETERMINING AN ECONOMICALLY JUSTIFIABLE PRICE FOR TRONTINEMAB IN EARLY ALZHEIMER'S DISEASE (ISPOR 2026) - "Patients treated with Trontinemab received increases in QALYs, however at considerable cost increases. Ultimately, despite increased reported efficacy compared to existing anti-amyloid options, trontinemab's cost effectiveness is subject to substantial uncertainty as results are based on a select report from very early clinical testing."

Alzheimer's Disease • CNS Disorders • Dementia

TRONTIER 1: A Study of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P3 | N=800 | Recruiting | Sponsor: Hoffmann-La Roche

Trial initiation date • Alzheimer's Disease • CNS Disorders • Dementia • Aβ42 • CSF Aβ42

NEXT-GENERATION NEURODEGENERATIVE DISEASES THERAPEUTICS WITH STRONG BINDING FOR AMYLOID-BETA/TAU/ALPHA-SYNUCLEIN AGGREGATES, REDUCED RISK OF ARIA, AND IMPROVED BRAIN DELIVERY. (ADPD 2026) - "Benchmark comparisons were made with Lecanemab, Trontinemab and other mAbs. Fusion to a new Fc domain activated phagocytosis of Aβ fibrils to levels comparable to Lecanemab while reducing TNF-α release by 50%. These results pave the way for the development of a next-generation therapeutic solution for mixed NDD pathologies like AD/PD."

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

DATA-DRIVEN APPROACHES TO REPRESENTATIVE US ENROLMENT PLANNING IN THE TRONTIER STUDIES OF TRONTINEMAB IN EARLY SYMPTOMATIC ALZHEIMER'S DISEASE (ADPD 2026) - "Characterizing AD trial sites and modelling the screening funnel with real-world data provided valuable tools for data-driven US site landscaping and representative enrollment planning in the TRONTIER studies."

Alzheimer's Disease • CNS Disorders