My Alzheimer's Journey
Part 122 - Trontinemab
Before I discuss Trontinemab, I want to show you a few photos I took earlier today. I had an appointment at Duke Health and I arrived early so I walked to the Sarah P. Duke Gardens. This is a 55 acre botanical garden on the Duke Campus. It is about one half mile from the Duke Health Clinics. Today was a perfect day (warm, sunny, and breezy) to wander around the garden. It is a peaceful place that has always been good for my soul.
What Is Trontinemab?
Trontinemab is a novel antibody made up of two components: gantenerumab and a delivery system called Brainshuttle. Trontinemab is engineered for enhanced access to the brain to enable rapid reduction of amyloid in people with Alzheimer’s disease (AD). It is developed by Roche.
How Does Trontinemab Compare to Lecanemab and Donanemab?
Trontinemab is an experimental drug designed to clear amyloid plaques faster and with fewer side effects (ARIA) than Lecanemab and Donanemab.
Gantenerumab (which works in a very similar way to Lecanemab and Donanemab) failed to significantly slow down AD progression in early trials. These early trials showed that gantenerumab on its own didn’t slow down AD progression because it was slower at removing amyloid. The results of the trial were based on measurements over 18 months. This may not have been long enough for it to have an effect.
Combining gantenerumab with the Brainshuttle delivery system, Trontinemab is thought to cross the blood-brain barrier much more efficiently than Lecanemab and Donanemab. If this proves to be true, Trontinemab will likely achieve similar or superior plaque reduction at significantly lower doses than Lecanemab and Donanemab.
What Is Brainshuttle Technology?
The Brainshuttle is a “fragment of an antibody” that interacts with cell-surface receptors on the blood-brain barrier. This interaction results in the Brianshuttle effectively penetrating the blood-brain barrier. If the Brainshuttle is carrying gantenerumab, it will be deposited deep within the brain.
Roche believes Brainshuttle might also carry “enzymes, oligonucleotides (short, synthetic single-stranded DNA or RNA molecules) or enable the delivery of specific gene therapies.”
When Will Trontinemab Be Available?
Roche began testing Trontinemab in their lab in 2012. Fourteen years later, Trontinemab is in its Phase 3 trial.
According to clinicaltrials.gov.:
Phase 3 began with two identical studies. TRONTIER 1 and 2 will treat 800 patients each with 3.6 mg/kg trontinemab or placebo monthly for six months, and then every three months for a total of 1.5 years. An open-label extension is offered. Participants will be amyloid-positive and have MCI or mild dementia, with less than four microhemorrhages, no siderosis, history of macrohemorrhage, or severe white-matter disease. ApoE4 homozygotes will be allowed. The primary endpoint is the CDR-SB; secondaries include MMSE, ADAS-Cog13, ADCS-ADLs, and global CDR score. Prescreening will use plasma p-tau217. The global trials will span 18 countries in North and South America, Asia, Europe, and Australia, with completion set for 2028.
If the Phase 3 results are positive, Roche will make the decision to apply for regulatory approval or not. Depending on a number of factors (which are not known at this point in time), it could take up to two years for regulatory approval and manufacturing to begin.
My best estimate is that the earliest Trontinemab could be available is late 2030.
Sources:
https://clinicaltrials.gov/study/NCT04639050
https://www.roche.com/solutions/pipeline
https://www.roche.com/media/releases/med-cor-2025-04-03
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