Nonclinical Safety Profile of Etelcalcetide, a Novel Peptide Calcimimetic for the Treatment of Secondary Hyperparathyroidism

Etelcalcetideis a novel d-amino acidpeptide that functions as an allosteric activator of the calcium-sensing receptorand is being developed as an intravenous calcimimeticfor the treatment of secondary hyperparathyroidismin patients with chronic kidney disease on hemodialysis. To support clinical development and marketing authorization, a comprehensive nonclinical safety package was generated. Primary adverse effectsincluded hypocalcemia, tremoring, and convulsions. Other adverse effectswere considered sequelae of stress associated with hypocalcemia. Cardiovascular safety evaluations in the dog revealed an anticipated prolongation of the corrected QT intervalthat was related to reductions in serum calcium. Etelcalcetidedid not affect the human ether-a-go-go gene ion channel current. Etelcalcetidewas mutagenic in some strains of Salmonella, however, based on the negative results in 2 in vitro and 2 in vivo mammalian genotoxicity assays, including a 28-day Muta mouse study, etelcalcetideis conside...