AAN 2026 | Emerging treatments for MS: BTK inhibitors, monoclonal antibodies, and CAR T-cells
Patricia Coyle, MD, Stony Brook Medicine, Lake Grove, NY, discusses several emerging treatments for multiple sclerosis (MS), including BTK inhibitors, monoclonal antibodies, and CAR T-cells. This interview took place at the 78th American Academy of Neurology (AAN) Annual Meeting in Chicago, IL.
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Transcript
Well, there are still BTK inhibitors to read out, remibrutinib in particular. There’s also an anti-CD40 ligand, frexalimab, that has had a positive Phase II trial and is in Phase III trials right now. That’s kind of an immune checkpoint cutoff. It’s a blocking antibody, but it stops CD40 from binding to CD40 ligand, which is very important in both adaptive and innate immunity. So it’s driving it down...
Well, there are still BTK inhibitors to read out, remibrutinib in particular. There’s also an anti-CD40 ligand, frexalimab, that has had a positive Phase II trial and is in Phase III trials right now. That’s kind of an immune checkpoint cutoff. It’s a blocking antibody, but it stops CD40 from binding to CD40 ligand, which is very important in both adaptive and innate immunity. So it’s driving it down. There’s also a monoclonal antibody against CD19 and FC gamma receptor 2B, which would be expressed on B cells. So this is another blocking or binding monoclonal antibody where the B cells are stopped from activating. That had a very positive Phase II, so-called MoonStone study, three months with a 95% suppression of gadolinium enhancement. CAR-T techniques are now being studied in MS, and this is very appealing because they’ve had such great success in rheumatoid arthritis and lupus, and they also give a personalized but a very long-lasting treatment with CD8 T cells turned on. You collect the CD8 T cells, you expand them, you use typically a viral vector to put in the antigen that you want the cells to target, and then you lower the cell count in the individuals and give them back those cytotoxic CD8 T cells to last for a long time. Those studies are ongoing. It’s a very interesting study with anti-CD3. CD3 is a pan T cell marker and actually was studied earlier in MS, but stopped because of some adverse event concerns. This is giving a very novel way of supplying the anti-CD3. It’s intranasal treatment. And it seems as though that allows the monoclonal antibody to enter the CNS. I’m saying that because the numbers are very small, but they use PET scan readout, and they decrease microglia activation in the patients. Normally, a monoclonal antibody only enters 0.1% into the CNS. This was a clear impact on the CNS, so this will be going to further studies.
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