Promising News for New Anti-Amyloid Antibody Treatment

danasrin

Sharing because I wish this was around when my mom was diagnosed with Alzheimer's...

There's a new drug that seems like it has a good chance of becoming a game-changer for Alzheimer's, called Trontinemab. It was developed by Roche

Alzforum.org posted an article today about this new antibody, the article summarizes the presentation given at the recent Alzheimer's Association conference
https://www.alzforum.org/news/conference-coverage/roche-spells-out-phase-three-plans-trontinemab

I'm very optimistic about this new anti-amyloid antibody. It has dramatically lower risk of ARIA than all previous antibodies and removes amyloid even more robustly and even deeper into the brain. It has a different Aβ target than lecanemab - it goes after the insoluble fibrils instead of protofibrils, so I am curious to see how it will perform in comparison in terms of slowing cognitive decline/disease progression.

The phase 3 study will begin this fall, and apparently prescreening to find participants (they call it the TRAVELLER test) has just started to roll out in the US/Canada. I think more prescreening sites will open soon (and hopefully in more countries), so far I was only able to find one site advertising it online (maybe ya'll can find more!)
https://hawaiineuroscience.com/2025-free-alzheimers-prescreening-traveller-test-for-50-to-90-years-old/

What exciting news!

LBC83

I was in attendance at the AAIC in Toronto, and attended the session with the presentation by Roche. I agree the news was exciting! Here are my notes from the session:

Bottom Line Up Front: Trontinemab, made by Roche, just completed aPhase 2 clinical trial and the results were presented. Roche is now planning a Phase 3 trial. Trontinemab is designed to more easily pass through the blood/brain barrier (which Roche calls Brainshuttle), so lower doses are required. There were four presentations: an intro by a Professor of Neurology in London, and then 3 presentations by Roche.

I almost fell out of my chair when the session began, as it was led by Dr Cummings, who is my favorite AD researcher.

The professor noted there are currently three ways for drugs to cross the blood/brain barrier. First is focused ultrasound, then cell membrane coating (I guess Leqembi/Kisunla use this method)? The third is something called receptor-mediated transcytosis. Trontinemab utilizes the 3rd method. The professor noted that with Leqembi & Kisunla, only about 1% of the active drug infused into our bodies makes it across the brain/blood barrier. I was astonished at that statistic.

They said the key metric for the drug is toget below 24 CL of amyloid in the brain. This condition is referred to as "amyloid clear". In the Phase 2 trial, 91% of the participants were below the amyloid positive threshold at 28 weeks, with substantial amyloid reduction in all participants. The ARIA-E rates were low (less than 5%). There was also a 27% reduction in pTau181. The first seven doses of Trontinemab are every 4 weeks, then every 12 weeks thereafter.

They are planning a Phase 3 trial starting this year with 1,600 participants across 18 countries. They are using a pre-screening program utilizing a quick cognitive test and a blood test. They hope this shortens the screening time compared to previous trials.

There was then a Q&A session. They had the Roche presenters plus some outside AD experts serve as a panel to address the questions. Cummings asked the outside experts their opinion on what they heard about the Phase 2 trial results with Trontinemab. Here are my notes from the Doctors / Researchers on the panel:

• Could barely contain myself from whooping. Deep & rapid clearance with very low ARIA is incredible.
• Data very exciting, very deep and rapid clearing on PET, hope this translates into more robust benefits (in terms of reduced cognitive decline, something not measured in the Phase 2 trial).
• Wonderful that all fluid-based biomarkers move in right direction
• One panelist was referred to as "Mr. Safety", as he apparently has strongly pushed on the safety of anti-amyloid drugs. His comments: We are all impressed by the rapid, extensive, and safe amyloid loading. Could be a new paradigm for treatment. Wish it didn't take so long to get Phase 3 results. Interesting to try to figure out, why is ARIA so low? It would be great to better understand this.

Dorse

I have been recently diagnosed with mild Alzheimers. I have been weighing out all options, considering Kinsunla. I find your article on this above research very interesting. Any idea of when this option could be available?

LBC83

Not for a while.

In their press release on July 28 announcing the results presented at AAIC, Roche (the company developing the drug) states the Phase 3 trial with Trontinemab for those with early symptomatic AD has an "initiation planned in 2025." The Phase 3 trials for Leqembi & Kisunla had people engaged in the the trial for 18 months. As a side note, this doesn't mean everybody received the active druge for 18 months - in the Kinsunla trial they switched people to placebo before 18 months if amyloid PET scans showed they were amyloid cleared. Also, it isn't as if everybody enrolled in the trial starts together on day 1. Rather, as people sign up for the trial, the start on the drug (or placebo). So maybe it takes 9 months to get the trial fully enrolled, then add 18 months after the last person enrolled, then add some trial for the company to crunch the numbers to assess the results. After all of that, if the trial was successful, they can apply for FDA approval.

The above process clearly takes a lot of time. As one of the key understandings about the new anti-amyloid drugs is the importance of starting early (when amyloid levels tend to be lower), it seems it would be in your best interest not to wait for FDA approval of Trontinemab. Perhaps asking about enrolling in the Trontinemab might be an option. But a neagtive about the approach used in the Trontinemab trial. For the Leqembi & Kisunla trials, both drug companies compared their drugs against some taking a placebo. Given that today we know the importance of starting an anti-amyloid drug early, it appears to me somewhat ethically dubious to start a trial with Trontinemab with half the people on the active drug and the other half on placebo. Instead, I'd think it more reasonable to compare Trontinemab with Leqembi or Kisunla (or in an ideal world, maybe a trial with all 3 drugs compared head-to-head). But who might find such a trial? Perhaps not Roche?!?

To conclude, it seems your best choice might be between starting on Leqembi & Kisunla ASAP (and you are apparently already leaning towards Kisunla, with the higher risk of ARIA, but with a faster clearance rate of amyloid). But I'm no medical expert, you clearly need to consult with your Doctor on this matter.

Link below to Roche press release about Trontinemab with a few words about the planned Phase 3 clinical trial.

https://www.roche.com/media/releases/med-cor-2025-07-28