Ofatumumab – A Potential Subcutaneous B-cell Therapy for Relapsing Multiple Sclerosis

Abstract

The central role of B cells in multiple sclerosis (MS) is well established. It is supported by scientific evidence for several mechanisms by which B cells contribute to neuroinflammation and disease regulation, and by clinical evidence of profound suppression of MS disease activity by B-cell-depleting agents, particularly monoclonal antibodies (mAbs) targeting the B cell surface molecule CD20. Ofatumumab is a third-generation fully-human immunoglobulin G-1κ mAb that recognises both the small and large extracellular loops of the CD20 molecule on B cells that are completely distinct from the epitopes on CD20 recognised by rituximab or ocrelizumab and are closer to the cell membrane. Effective depletion of B cells is accomplished mainly via a mechanism of complement-dependent cytotoxicity. Ofatumumab, administered by monthly subcutaneous injections, demonstrated high efficacy in suppressing clinical and magnetic resonance image disease activity in patients with relapsing MS, which was associated with dose-dependent B-cell depletion and faster repletion than other anti-CD20-depleting mAbs. This, combined with a favourable safety profile, good tolerability, low immunogenic risk profile and convenient subcutaneous administration, make ofatumumab an attractive treatment option for active relapsing MS. With some similarities to ocrelizumab, a humanised anti-CD20-depleting mAb that is approved for the treatment of relapsing and primary progressive MS, there are still open questions regarding the long-term efficacy and safety of ofatumumab that should be addressed by further research and careful surveillance programmes.