Another B cell inhibitor against MSanother one antibody. Frexalimab would probably only get half the attention compared to the number of active ingredients with a similar mode of action that have already been approved. If this anti-CD40L antibody wasn’t related to EBV, the Epstein-Barr virus. The virus that is classified as (partially) suspicious for the development of MS.
If So the Epstein-Barr virus is actually one of the causes of multiple sclerosis (there are many indications that this is the case) and if Frexalimab can specifically deactivate B cells in this way and thus slow down the MS – both of which still have to be proven with certainty -, then Frexalimab, if approved, would be a treatment option for many people with MS. – If that’s too many ifs and ifs for you, it’s better to wait for the results of the phase 3 studies on frexalimab instead of reading on here.
Frexalimab and the Epstein-Barr virus
The details: Unlike ocrelizumab, ofatumumab, and ubituximab, frexalimab doesn’t deplete (ie, destroy) B cells in the peripheral blood, it just stops them from being activated. This happens via the ligand of CD40, called CD40L on T cells. Because in order to activate B cells (and also to get T cells on board), you not only need an antibody (e.g. a virus) that can bind to receptors, but other signaling pathways have to be activated, such as the connection of CD40 and CD40 ligand. Without this signaling pathway, the intervention of this part of the immune system is not activated. Frexalimab blocks exactly this signaling pathway.
The Epstein-Barr virus, in turn, causes more CD40L to be expressed in infected B cells. This one necessary signaling pathway is always activated in these cells. And it is precisely these cells that Frexalimab (among others) could block and thus slow down the progression of MS.
In a recently published phase 2 study in patients with relapsing forms of MS, this was achieved in comparison with placebo. Frexalimab was able to significantly reduce lesion burden and neurofilament light chains (plasma Nfl). Nfl values in the blood serve – so far only in studies – as a biomarker for the progression of the disease in multiple sclerosis (amsel.de had reported).
Range of side effects so far in the expected range
In studies, the antibody proved to be safe. In terms of side effects, frexalimab led to headaches and mild to moderate Covid 19 infections in the just over 100 patients in the two drug arms. An increased tendency to infection would be in this form of the immune modulation expect. Out of sequence and only in one patient in the lower active drug arm dose there was an increase in the ALT value of the liver. Frexalimab is currently used as a infusion administered; however, subcutaneous injection would theoretically also be possible.
Effect and side effect weighed against each other plus the possibility latent targeted deactivation of B cells infected with EBV – this makes Frexalimab an interesting drug. The continuation of the phase 2 study and phase 3 studies with a significantly larger number of subjects will have to show more details.