Etelcalcetide (Parsabiv®): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Etelcalcetide, marketed under the brand name Parsabiv®, is a second-generation, intravenous calcimimetic agent developed for the management of secondary hyperparathyroidism (SHPT) in adult patients with chronic kidney disease (CKD) undergoing hemodialysis. As a synthetic oligopeptide, its primary mechanism of action is the agonism of the calcium-sensing receptor (CaSR) on the parathyroid gland, which suppresses the synthesis and secretion of parathyroid hormone (PTH). This action leads to subsequent reductions in serum calcium and phosphorus levels, addressing the core biochemical derangements of SHPT.

Clinical development has established Etelcalcetide's superior efficacy in reducing PTH levels compared to both placebo and the first-generation oral calcimimetic, cinacalcet. Pivotal Phase III trials demonstrated that a significantly greater proportion of patients treated with Etelcalcetide achieved clinically meaningful reductions in PTH. A key advantage of Etelcalcetide is its intravenous route of administration, which is performed by healthcare professionals at the end of each hemodialysis session. This approach guarantees 100% bioavailability and completely bypasses the significant patient adherence challenges associated with daily oral therapies like cinacalcet, a factor that amplifies its efficacy in real-world clinical practice.

The primary safety consideration for Etelcalcetide is its potent calcium-lowering effect, which can lead to hypocalcemia. This on-target effect necessitates a rigorous risk management protocol, including contraindication in patients with low baseline calcium and a strict schedule for monitoring serum calcium and PTH levels, particularly upon initiation and after any dose adjustment.