Fp031etelcalcetide (Parsabiv®, Amg 416/Ono-5163) Directly Reduced Parathyroid Hormone Levels in Human Parathyroid Cell Culture

INTRODUCTION: Etelcalcetide (Parsabiv®, AMG 416/ONO-5163) is a novel allosteric modulator for the calcium-sensing receptor. In in vitro studies, etelcalcetide directly reduced parathyroid hormone (PTH) levels in rat parathyroid cell and tissue culture. In in vivo studies, etelcalcetide reduced PTH levels in subtotal nephrectomized rats and in hemodialysis patients with secondary hyperparathyroidism (SHPT). However, the direct effect of etelcalcetide on PTH secretion in human parathyroid cell culture have not been reported. The purpose of the present study is to elucidate whether etelcalcetide has a direct effect on PTH secretion in human parathyroid cell culture in vitro. METHODS: In the interim analysis, we used 10 of human parathyroid tissues by parathyroidectomies (Each patient signed an informed consent form before surgeries). All parathyroid tumors were obtained from primary hyperparathyroidism (PHPT) patients. Each parathyroid tissue was dispersed with collagenase for 5 min and resuspended in culture medium. Cells were seeded into 96-well plates at approximately 3 x 10⁵ cells/well. Following 2h incubation with etelcalcetide, incubated media was collected. Final concentrations of etelcalcetide in the media were from 0.005 to 50 μM in the presence of extracellular calcium (Ca). Human PTH concentration in the media were determined using PTH-ELISA kit (Immunotopics, ltd). RESULTS: In the interim analysis, Ca and etelcalcetide reduced PTH levels in human parathyroid cell culture. EC50 values of etelcalcetide in the typical sample were approximately 0.57μM, 20.84μM and 0.42μM, respectively. EC50 values of two samples were similar to the plasma concentration of Japanese SHPT patients (0.34μM at 5 mg/ person). CONCLUSIONS: These results demonstrated that etelcalcetide directly reduced PTH secretion in human parathyroid cell culture in vitro. Further studies would be elucidated using human parathyroid cells from not only PHPT patients but also SHPT patients.