SHERIDAN, WYOMING – July 29, 2025 – Roche has unveiled compelling early-stage data for its next-generation Alzheimer’s therapy, trontinemab, which demonstrated rapid and deep amyloid plaque clearance in patients after just seven months of treatment. The findings, presented at the 2025 Alzheimer’s Association International Conference in Toronto, suggest a potential leap beyond first-generation FDA-approved antibodies and set the stage for a new class of blood-brain barrier-penetrating biologics.
Trontinemab achieves over 90% amyloid clearance in seven months
In the Phase Ib/IIa Brainshuttle AD trial, 91% of participants receiving the highest dose of trontinemab (3.6 mg/kg) became amyloid-negative on PET scans within seven months. Notably, 72% achieved "deep clearance" on standardized plaque rating scales—a level of response that typically requires over 18 months with currently approved therapies.
- 49 out of 54 patients on high-dose trontinemab showed amyloid clearance
- 39 of those achieved deep plaque removal
- Clearance speed and depth outperformed Biogen/Eisai’s Leqembi and Lilly’s Kisunla
Analysts from B. Riley Securities called the data a "paradigm shift" in Alzheimer’s antibody development, citing the rapid response rate as a key differentiator over existing therapies.
Enhanced brain penetration marks key technical leap
Trontinemab uses Roche’s proprietary Brainshuttle platform, which fuses an anti-amyloid antibody with a transferrin receptor-binding module. This design enhances the molecule’s ability to cross the blood-brain barrier—one of the largest hurdles in central nervous system drug development.
The result: greater therapeutic concentration in brain tissue, enabling faster clearance of neurotoxic amyloid plaques with potentially lower systemic exposure.
This mechanism may validate the blood-brain delivery approaches pursued by other biotechs like Denali Therapeutics and Cognition Therapeutics, which are also targeting neurodegenerative diseases with enhanced transport technologies.
Industry trend: moving beyond symptom delay toward early intervention
While trontinemab has yet to demonstrate cognitive benefit, its rapid plaque clearance may enable future trials to shift focus from symptomatic patients to those in preclinical or prodromal stages—those at risk but not yet impaired.
Roche has already announced two planned Phase III trials, TRONIER 1 and 2, scheduled to begin in 2025. These studies will assess whether early intervention with trontinemab can slow or prevent disease progression in high-risk populations.
This strategy aligns with growing momentum in the Alzheimer’s field to prioritize early diagnosis and disease-modifying treatment before irreversible brain damage occurs.
Safety profile compares favorably with first-gen antibodies
Amyloid-related imaging abnormalities (ARIAs) remain a key concern for anti-amyloid therapies. Among the 149 patients treated with trontinemab across all dose levels, only four cases of ARIA were reported—significantly lower than the rates seen in patients on Leqembi or Kisunla.
However, the trial did include one serious adverse event. A 78-year-old woman died of a brain hemorrhage six weeks into treatment. According to Endpoints News, her imaging revealed superficial siderosis—a known ARIA risk factor—underscoring the need for improved screening and monitoring protocols in future trials.
“This level and speed of clearance beat out what Leqembi and Kisunla achieved even after 18 plus months of treatment.” — B. Riley Securities
Strategic implications for providers and pipeline players
Trontinemab’s early success not only positions Roche to re-enter the Alzheimer’s race after its prior gantenerumab setback but also provides clinical validation for companies developing novel CNS delivery systems.
Hospitals and neurologists may eventually benefit from faster-acting therapies with fewer infusions, lower ARIA risks, and potential utility in asymptomatic populations—changing the trajectory of Alzheimer’s care from reactive to proactive.
For biotech peers, the Brainshuttle platform’s progress lowers perceived risks for next-gen approaches seeking improved brain penetration, encouraging further innovation in neurodegenerative treatment pipelines.
Learn more at https://www.roche.com