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

• DOI: 10.1016/j.jim.2016.10.006
• Publication Date: 2016-10-24T19:30:28Z
• Authors: Andrew C. Melton; Russell K. Soon; Troy Tompkins; Brian Long; Becky Schweighardt; Yulan Qi; Catherine Vitelli; Anil Bagri; Celeste Decker; Charles A. O'Neill; Stephen J. Zoog; Lynne Jesaitis
• Keywords: Pharmacodynamics

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