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Kidney Week

Abstract: FR-PO290

The Novel Calcimimetic Agent Evocalcet (MT-4580/KHK7580) Has a Potential for the Treatment of Hyperparathyroidism with Less Effect on the Gastrointestinal Motility In Vivo Models

Session Information

Category: Mineral Disease

  • 1202 Mineral Disease: Vitamin D, PTH, FGF-23


  • Tokunaga, Shin, Kyowa Hakko Kirin Co., Ltd., Shizuoka, Japan
  • Yoneda, Hikaru, Mitsubishi Tanabe Pharma Corporation., Saitama, Japan
  • Fukagawa, Masafumi, Tokai University School of Medicine, Isehara, kanagawa, Japan
  • Akizawa, Tadao, Showa University School of Medicine, Tokyo, Japan
  • Ueno, Kimihisa, Kyowa Hakko Kirin Co., Ltd., Shizuoka, Japan
  • Shimazaki, Ryutaro, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan
  • Kawata, Takehisa, Kyowa Hakko Kirin Co., Ltd., Shizuoka, Japan

Cinacalcet is widely used for the management of secondary hyperparathyroidism (SHPT). Nevertheless, cinacalcet has adverse effects on the gastrointestinal (GI) tract, which sometimes causes poor compliance or discontinuation of the treatment. Evocalcet (MT-4580/KHK7580) is a novel oral calcimimetic compound developed for dialysis patients with SHPT and is expected to improve upon several issues associated with cinacalcet. The objective of present preclinical study was to confirm the characteristics of evocalcet as a calcimimetic agent and to evaluate its effects on GI tract.


In vitro and in vivo pharmacological studies (using HEK293 cells expressing human calcium receptor and 5/6 nephrectomized rats) were conducted. To compare the effects of evocalcet and cinacalcet on GI tract, the emetic responses by each compound in common marmosets and gastric emptying in rats were evaluated. In addition, the binding affinity of some vomiting-associated receptors was assessed.


The pharmacodynamic properties of evocalcet were similar to those of calcimimetics. In marmosets, evocalcet achieved wider safety margin between dosages which induced emesis or PTH reduction compared to cinacalcet. Although cinacalcet caused significant delay in gastric emptying in rats, evocalcet had no marked effect on gastric emptying at doses that showed similar pharmacological activity to cinacalcet (Table 1). Evocalcet had lower binding affinities to vomiting-associated receptors, such as dopamine, cannabinoid, opioid, serotonin, and other receptors compared with cinacalcet.


Evocalcet has a potential as the novel oral calcimimetic agent with better safety profile and medication adherence than cinacalcet for the treatment of SHPT.

Table 1. The effects of evocalcet and cinacalcet on gastric emptying in rats
TreatmentDosage (mg/kg)Gastric emptying (%)
Vehicle-65.50 ± 5.01
Evocalcet0.367.83 ± 5.44
165.89 ± 4.71
361.58 ± 4.58
Cinacalcet1055.17 ± 2.88
3035.72 ± 5.64 ***
10020.02 ± 5.52 ***

n=7~8, Mean ± SE. ***: p<0.001 compared with vehicle group.