In a Phase Ib/IIa trial, 91% of patients receiving the highest dose of trontinemab were amyloid negative after seven months of treatment, representing what B. Riley Securities called a “paradigm shift” to first-generation FDA-approved antibodies.
Roche touted rapid amyloid clearance from the brains of patients with Alzheimer’s disease after treatment with its anti-amyloid antibody trontinemab on Sunday.
In a highly anticipated presentation at the Alzheimer’s Association International Conference 2025 in Toronto, Roche revealed data from its ongoing Phase Ib/IIa Brainshuttle AD trial. In the dose-expansion section of the study, 91% of patients (49 of 54) who received the higher dose level of trontinemab, 3.6 mg/kg, were amyloid negative on a PET scan after seven months of treatment, while 72% (39 patients) saw “deep clearance” of plaques, as rated on a common plaque deposit measuring scale.
Analysts at B. Riley Securities on Monday wrote that the data “represents a paradigm shift” to first-generation FDA-approved antibodies, specifically noting Biogen and Eisai’s Leqembi and Eli Lilly’s Kisunla.
Noting that treatment with trontinemab led to a “90%+ reduction from baseline with nearly all trontinemab -treated patients responding,” the analysts said this level and speed of clearance beat out what Leqembi and Kisunla achieved even after 18 plus months of treatment.
The Brainshuttle AD results come more than five years after Roche’s previous attempt at an Alzheimer’s antibody, gantenerumab, fell flat. In February 2020, Roche’s Genentech reported that gantenerumab missed the primary endpoint of a Phase III trial and the company halted development.
Safety was also a highlight for Roche this time around. Amyloid-related imaging abnormalities (ARIAs), signifying brain lesions or swelling, are a known risk of anti-amyloid antibodies. Four of the total 149 patients treated with trontinemab across all doses had ARIAs. These abnormalities have dogged Biogen’s and Lilly’s drugs, reaching rates into the teens in tested patients with Leqembi.
The news wasn’t all rosy though—Endpoints News reported that one trial participant, a 78-year-old woman, died of a brain hemorrhage. Her death occurred six weeks into the study. A scan of her brain showed an abnormal accumulation of iron called superficial siderosis that is a risk factor for ARIA, according to the publication.
Though the data from this trial do not signify an actual ability to treat Alzheimer’s disease or reduce symptoms, the results are significant enough to validate other companies’ therapeutic approaches, according to B. Riley. Trontinemab’s mechanism of action combines an antibody’s ability to bind amyloid with the capacity to bind a transferrin receptor shuttle module, allowing it to more ably cross the blood-brain barrier and penetrate into the brain.
The Brainshuttle trial success de-risks companies like Denali and Cognition, according to the B. Riley analysts. Both companies are targeting neurodegenerative diseases—including Alzheimer’s, Parkinson’s and Hunter syndrome—with tech to better ferry drugs into the brain.
In Sunday’s press release Roche also announced plans for two Phase III trials, TRONIER 1 and 2, to start sometime in 2025. Those trials will focus on patients at risk of cognitive decline, aiming to slow or prevent Alzheimer’s disease progression.
