Pharmacological properties and clinical trial results of the novel calcium-sensing receptor agonist upacicalcet sodium hydrate (Upacita^® intravenous injection for dialysis)

Abstract

Upacicalcet sodium hydrate (upacicalcet) is a novel small-molecule calcium-sensing receptor (CaSR) modulator with an amino acid structure, developed in Japan as a derivative from research into taste enhancement. Upacicalcet specifically targets CaSR and is thought to inhibit parathyroid hormone (PTH) secretion by activating the receptor in the presence of extracellular calcium (Ca). In nonclinical studies, upacicalcet was evaluated for its pharmacological properties, binding characteristics, and effects on ectopic calcification, parathyroid hyperplasia, and bone disorders associated with secondary hyperparathyroidism (SHPT). The results supported its mechanisms of action, binding mode, and efficacy in suppressing disease progression. In clinical trials, upacicalcet demonstrated efficacy and safety in patients with SHPT undergoing hemodialysis, as assessed in domestic Phase I/II trial (AJ1001 trial), Phase II trial (AJ1002 trial), Phase III placebo-controlled trial (AJ1004 trial), and Phase III long-term administration trial (AJ1003 trial). Upacicalcet was approved in June 2021 for the treatment of secondary hyperparathyroidism (SHPT) in patients undergoing hemodialysis and was launched in August of the same year.