Antibodies that neutralize cellular uptake of elosulfase alfa are not associated with reduced efficacy or pharmacodynamic effect in individuals with Morquio A syndrome

Abstract Many enzyme replacement therapies(ERTs) for lysosomal storage disordersuse the cell-surface cation-independent mannose-6 phosphate receptor(CI-M6PR) to deliver ERTs to the lysosome. However, neutralizing antibodies (NAb) may interfere with this process. We previously reported that most individuals with Morquio A who received elosulfase alfain the phase 3 MOR-004 trial tested positive for NAbs capable of interfering with binding to CI-M6PR ectodomainin an ELISA-based assay. However, no correlation was detected between NAb occurrence and clinical efficacy or pharmacodynamics. To quantify and better characterize the impact of NAbs, we developed a functional cell- based flowcytometry assay with a titerstep that detects antibodies capable of interfering with elosulfase alfauptake. Serum samples collected during the MOR-004 trial were tested and titerswere determined. Consistent with earlier findings on NAb positivity, no correlations were observed between NAb titersand the clinical outcomes of elosulfase alfa-treated individuals with Morquio A.