Ianalumab is an investigational human monoclonal antibody that features a dual mechanism of action to treat B-cell-driven autoimmune diseases.
It targets the B-cell activating factor receptor (BAFF-R) to simultaneously destroy pathogenic B cells and stop the survival signals that allow remaining autoreactive cells to thrive.
The dual-action process operates in two specific ways:
B-Cell Depletion (ADCC): Ianalumab is an afucosylated antibody, which gives it a much stronger binding affinity to immune effector cells like natural killer (NK) cells.
This interaction triggers a process called antibody-dependent cellular cytotoxicity (ADCC).
The effector cells destroy the targeted B cells, depleting them both in the blood and affected tissues.
B-cell activating factor (BAFF-R) blockade: In autoimmune diseases, high levels of BAFF (B-cell activating factor) normally bind to BAFF-R to promote B-cell survival, activation, and proliferation.
By binding to the receptor, ianalumab acts as a competitive antagonist, physically blocking BAFF from interacting with it.
This cuts off the crucial survival signals needed by both mature and newly developing B cells.
By combining these two actions, ianalumab prevents the formation of autoantibodies and reduces overall inflammatory disease activity.
This targeted approach is currently under clinical evaluation and development by Novartis for conditions like Sjögren’s disease, systemic lupus erythematosus (SLE), and immune thrombocytopenia (ITP).