Horizon Therapeutics plc announced data from the Phase 3 pivotal trial of UPLIZNA in NMOSD illustrating the treatment's effectiveness among patients with different genetic make-ups, including those with certain variations associated with reduced response to conventional monoclonal antibody (mAb) therapies. These data are being presented during the Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, June 1-4. Treatment for NMOSD includes the use of mAbs that bind to and deplete the B cells that drive disease activity. Increasingly, therapeutic research has shown that genetic variations in the immune system can affect the efficacy of these mAb therapies.

Specifically, a variation, or polymorphism, in a gene that encodes the low-affinity Fc gamma receptor IIIa (FCGR3A) has been shown to reduce the effectiveness of certain mAbs, like rituximab, in diseases including NMOSD.(1-6) UPLIZNA is a highly specific CD19 B-cell depleting agent that targets an extended range of B cells, including plasmablasts and plasma cells, which contribute to NMOSD. UPLIZNA was purposely engineered to allow for strong binding to the low-affinity Fc gamma receptor IIIa (FCGR3A). This molecular engineering has been shown to improve efficacy in patients regardless of FCGR3A genotype.(7-8) Data from the N-MOmentum pivotal trial of UPLIZNA (NCT02200770) illustrates the potential advantage of the design of UPLIZNA.

As part of the trial, 142 participants underwent genotyping to identify FCGR3A genotype. The study found no significant differences in disease attacks or disability regardless of FCGR3A genotype, indicating the design of UPLIZNA was effective even among those whose polymorphism is associated with reduced efficacy of other treatments.