ACTRIMS 2026 | Results of the Phase II MoonStone study of obexelimab in relapsing multiple sclerosis

So the MoonStone was a 12-week Phase II study of obexelimab in relapsing MS. And obexelimab is an interesting humanized bifunctional monoclonal antibody. It targets on one end the CD19 molecule, like other anti-CD19 antibodies, but also the inhibitory receptor, the Fc gamma receptor 2B, which delivers negative signals into the cell. And rather than being a depleter of B-cells primarily, it actually modulates the response of the B-cells, and it binds to the lineage of cells that express CD19, which of course is quite a broad range, even broader than CD20, in that CD19 is present on some of the earlier cells and some of the later cells, such as the plasmablasts. All these cells have been shown, both in vitro and in animal models, to have modulated responses with a binding rather than depletion. And the modulation is an anti-inflammatory modulation. So Moonstone was a double-blind, randomized, placebo-controlled trial, 12 weeks long, and then a transition from placebo to open-label obexelimab. The primary outcome measure was the impact of obexelimab on new GAD lesions based on the MRI. The randomization was successful, very well balanced at baseline in terms of age, female to male proportion, time from diagnosis, and EDSS, with individuals being in the early 40s at entry with an EDSS of 2.5 to 3, and about 20% of whom had GAD lesions at baseline. The primary endpoint was met with a 95% relative reduction in the development of new GAD lesions at weeks 8 and 12 of the blinded phase of the study. And this translated into the same kind of impact seen on new enlarging T2 lesions, such that really the development of new focal disease activity was very substantially abrogated with the obexelimab as compared to the placebo. And importantly, and as predicted, while the B-cell counts were diminished in their circulation, they were not decreased nearly to the extent of the typical anti-CD20 or anti-CD19 monoclonal antibodies, and the mean remained well above the lower limit of normal, again making the point that one can achieve with this intervention high efficacy on focal inflammatory disease or relapsing disease without having the same depleting impact on the B-cells. From a safety and tolerability standpoint, for the most part, this was really limited to injection site reactions that were largely mild, grade one, and in essence involved some erythema and on occasion some itchiness. But otherwise, things were quite well balanced between the obexelimab and placebo group, perhaps with the exception of a slight increase in run-of-the-mill urinary tract infections in the obexelimab versus placebo cohort. And from the standpoint of adverse events of special interest, again, very little in the way of hypersensitivity, a slight increased signal of infection. There were only three treatment emergent serious adverse events. One bacterial infection, which was not deemed related to the drug and was resolved. The drug was interrupted temporarily and reinstated. Another infection that was deemed related and resolved. There was the intent to restart study drug, but because of concern over unblinding, the drug was not continued. And then a single hypersensitivity reaction, which resolved with treatment discontinuation. So overall, obexelimab is an intervention that targets CD19 and the Fc gamma receptor. It modulates B-cell immune response with limited depletion and resulted in near complete suppression of new brain lesions on MRI in a 12-week blinded randomized placebo-controlled study and was generally well-tolerated with no surprising safety features. And obviously, good data to support it being pursued further in terms of a Phase III trial program.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.