Felzartamab (MOR202) is a therapeutic human monoclonal antibody derived from MorphoSys’ HuCAL antibody library and directed against CD38. Felzartamab is currently under clinical investigation in patients with anti-PLA2R antibody-positive membranous nephropathy, a kidney specific autoimmune disease, and in patients with multiple myeloma. In the future, Felzartamab might potentially be evaluated as targeting therapy in additional autoimmune mediated diseases. End of 2017, MorphoSys entered into an exclusive regional licensing agreement with I-Mab Biopharma to develop and commercialize Felzartamab in Greater China.
Therapeutic fields and proposed mode of action
Anti-PLA2R Antibody-positive Membranous Nephropathy
Anti-PLA2R antibody-positive Membranous Nephropathy is an immune disease caused by autoantibodies against kidney cells. Membranous nephropathy is the leading cause of nephrotic syndrome in adults. Around 80% of membranous nephropathy (MN) cases are primary with an autoimmune nature, while only 20% are secondary and related to other diseases or exposures. The natural course of MN is variable and unpredictable: 50% of patients diagnosed with primary MN continue to have nephrotic syndrome and 30% of patients may progress to end-stage renal disease over 10 years (Keri, 2019). Moreover, patients with MN remaining nephrotic are at increased risk for thromboembolic and cardiovascular events.
PLA2R is a membrane glycoprotein expressed in epithelial cells in normal human glomeruli. Under autoimmune pathological condition, the immune system of MN patients reacts against PLA2R by producing specific autoantibodies. Binding of such autoantibodies to PLA2R induces inflammatory processes which can end up in thickening of the glomerular membrane and finally may lead to nephrotic syndrome (see cartoon).
Currently, there is no approved standard treatment for autoantibody-positive MN. The current treatment regimen mainly comprises off-label use of various non-immunosuppressive drugs (e.g. ACE inhibitors or Angiotensin Receptor Blockers, statins and diuretics), conventional immunosuppressive drugs (e.g. cyclophosphamide combined with steroids, calcineurin inhibitors, Mycophenolat-Mofetil) and targeted immunosuppressive drugs (i.e. anti-CD20 antibodies) (Couser WG, 2017; Bomback AS, 2018)