ACTRIMS 2026 | Highlights from ACTRIMS 2026: brain atrophy as a clinical trial endpoint and the FENtrepid trial

There was a great discussion on discordant results more recently between clinical progression and brain atrophy as a measurement, as an outcome measurement. And traditionally, we had seen that clinical progression and brain atrophy correlated really well, and that brain atrophy could be used as a potential outcome measure in Phase II trials to bring drugs to Phase III studies. With the more recent trials, particularly HERCULES, as well as O’HAND, some of the more recent statin trials as well, and lipoic acid, there seemed to be more discrepancy between clinical progression and MRI atrophy, which suggests that it might no longer be an appropriate surrogate depending on what drug we’re looking at in terms of the mechanism of action. So if we’re expecting a drug to have a more CNS penetrant effect, that then atrophy might not be a good surrogate marker for us to identify which drugs we can bring to Phase III studies. I think that has significant implications as a field in terms of where do we go and how do we then bring drugs to market? How do we screen drugs to be effective? And how do we use better markers to identify what’s actually happening with our patients? And I think it brings up an interesting topic as to where do we go from here and where do we move? And as a field, we don’t quite have an answer yet. We’re grappling with those decisions as always more research is needed, but I think it brings up a very interesting point in forcing us to kind of rethink how we look at that difference between what we’re seeing from our patients in the real world and clinical progression versus what our surrogate markers are. And again, better biomarkers, more accurate and appropriate biomarkers are always needed for our patients.

I am excited by the fenebrutinib data. There is some interesting study being presented looking at how, or FENtrepid results were presented where they were looking at patients who were being treated with fenebrutinib versus ocrelizumab. And what’s exciting about that is because ocrelizumab has become such a drug that is so widely used now because of its high efficacy rate, how well it works for patients and how well they tolerate it, that we want to make sure that when we’re thinking about new therapies, we kind of want to compare it to the current standard. And the benefit of fenebrutinib was exactly that. It was a trial comparing how patients did on fenebrutinib compared to ocrelizumab. And it showed, you know, so the study was demonstrating non-inferiority, again, confirming that Ocrevus works really well on disability outcomes for patients and that if it works so well, it’s hard to prove that a drug does better. So it’s nice that fenebrutinib does not do worse, so non-inferior. And that gives us options for our patients, meaning if they can’t tolerate ocrelizumab for whatever reason, they have safety concerns, other issues, we have a potential therapy that helps with progression in a way without compromising some of the efficacy that we would be concerned about if we switch them off of such a highly efficacious medication such as ocrelizumab. So I’m certainly excited to see options for our patients, more options, more availability, allowing us to kind of move closer and closer to that individualized treatment that we really need for our care for our patients.

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