Development of evocalcet for unmet needs among calcimimetic agents

ABSTRACT

Introduction

The calcium-sensing receptor is an important treatment target for secondary hyperparathyroidism (SHPT) in patients undergoing dialysis. In addition to vitamin D receptor activator, cinacalcet has recently been widely used for SHPT management, and the significant suppression of parathyroid hormone (PTH) with better control of serum calcium and phosphorus has been reported. However, low adherence and insufficient dose escalation mainly due to frequent gastrointestinal adverse events, still remain as major issues. To overcome these unmet needs, we have developed a new oral calcimimetic agent evocalcet, which has recently been approved by the Pharmaceutical Affairs Act in Japan.

Areas covered

PubMed was searched from inception until April 2020 with the word evocalcet to summarize the development of this new calcimimetic agent, its pharmacokinetics, and the results of clinical trials, along with an overview of the differences among calcimimetic agents. This review also includes the management of SHPT with a focus on calcimimetics.

Expert opinion

Evocalcet evoked fewer gastrointestinal-related adverse events while suppressing PTH at a lower dose than cinacalcet. These data suggest evocalcet may contribute to better adherence and sufficient dose escalation in patients with SHPT. Whether or not evocalcet improves clinical outcomes remains to be elucidated.

KEYWORDS:

• Calcimimetics
• calcium-sensing receptor
• evocalcet
• parathyroid hormone
• secondary hyperparathyroidism
• cinacalcet
• chronic kidney disease
• end-stage renal disease
• dialysis

Article highlights

• A new calcimimetic, evocalcet, was developed and approved in 2018 in Japan for dialysis patients with SHPT, and also recently for refractory parathyroid carcinoma or primary hyperparathyroidism.

• Evocalcet has the same PTH-reducing effect as cinacalcet but at a lower dose because of a higher bioavailability.

• Evocalcet induces less gastrointestinal-related AEs but comparable incidence of hypocalcemia as cinacalcet.

• Drug-drug interactions of evocalcet are attenuated compared with cinacalcet.

Declaration of interest

M Fukagawa has received honoraria, consulting fees, grant and research support from Astellas Pharma, Bayer Yakuhin, EA Pharma Co Ltd, Kissei Pharmaceutical, Kyowa Kirin, Ono Pharmaceutical, and Torii Pharmaceutical. T Kawata is an employee of Kyowa Kirin Ltd. Y Endo is an employee of Kyowa Kirin Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Information resources

Additional information on evocalcet can be found in the following referenced articles: Kawata 2018 [51], Akizawa 2018 [57] and Fukagawa 2018 [58].

Additional information

Funding

Language editing services were funded by Kyowa Kirin LTD.