AAN 2026 | Phase II open-label extension of frexalimab in participants with relapsing multiple sclerosis

So let me discuss with you the key data of the extension period of the frexalimab study. Frexalimab is a monoclonal antibody targeting anti-CD40 ligand. The pathway CD40 and CD40 ligand is very important in many inflammatory conditions, not only MS, but also involved in lupus, for example. It’s a key element of the activation of adaptive immunity, so mainly B- and T-lymphocytes, but also activating innate immunity, the myeloid cells, macrophages, microglia, but also dendritic cells. So blocking this pathway may change a lot the inflammation in tissues. So, of course, we know for a long period of time that this pathway is involved in MS. So the story is already long because 20 years ago, it was tested with the first generation of anti-CD40 ligand monoclonal. But the studies at that time were stopped because of safety issues with thromboembolic events. Now, with a new generation of this monoclonal, it’s overcome this issue. And up to now, we have no thromboembolic events. Because, in fact, the CD40 was also expressed at the surface of the endothelium and also on platelets. So inhibiting CD40 ligand provokes aggregation of platelets into small vessels, so contributing to a higher risk of thrombosis. So the Phase II data using frexalimab in relapsing-remitting MS was published last year in the New England Journal of Medicine. Two doses of frexalimab, one subcutaneous, the other IV, were compared to a placebo arm. The primary endpoint was relapse rate after only 12 weeks, and it was the number of new Gad-positive lesions, and also during the short period of extension, some clinical efficacy and data concerning safety. So the primary endpoint was met with almost 90% decrease of the number of new Gad-positive lesions with a high dose using IV route. During the extension period, and now I have presented at this American Academy in Chicago, maybe the three years extension of frexalimab. So after the Phase II, all the patients, because of efficacy, switched from placebo to the active frexalimab. And now we have maybe from the onset, 150 patients approximately included in the core study. And until three years, we have almost 80% still treated with frexalimab, which is very good, in fact. 80% after three years, it’s a very good point. And what we observe, that in patients already treated with frexalimab from onset, we maintain an extremely low number of Gad-positive lesions, extremely low also, a new T2. And also, in patients switching from placebo to frexalimab, high dose, subcut or IV, we have an equivalence between the subcut route and the IV route. We have also a very important decrease of the number of Gad-positive lesions, which is extremely interesting indeed. We have also around 86% with no clinical relapse during this three-year period. 86% relapse-free. Also interesting, we have no change in the mean EDSS for the whole cohort of patients. And also, we have interesting biomarkers. Rapidly, we have a decrease in the level of the neurofilament in the plasma, rapidly in the range of the normal population, and remain stable over time. And again, we have also a significant decrease of another chemokine, CXCL13. Also, CXCL13 is interesting because it’s a cytokine involved the recruitment of B lymphocytes, which is also an important target in MS. And also a decrease in the rate, very low rate of atrophy globally for the whole period. And more interesting, because it was a Phase II, an extension of the Phase II, safety is important. We have absolutely no signal concerning safety. No change in the lymphocyte count, no change in the immunoglobulin levels, no increased risk of infection, no data concerning some safety of the liver, for example. So we have both clinical aspects, MRI data, biomarker and safety data, very encouraging. And as you probably know, many patients are already included in the Phase III program with FREVIVA, which is a study evaluating frexalimab in the non-relapsing SPMS and FREXALT in relapsing-remitting MS. But we need to wait approximately two years to have the data.

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