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Abstract: TH-PO157

ORCHESTRA Trial: Head-to-Head Comparison of Oral Calcimimetics Evocalcet and Cinacalcet in East Asian Hemodialysis Patients With Secondary Hyperparathyroidism

Session Information

  • CKD-MBD: Targets and Outcomes
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Liang, Xinling, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
  • Ni, Zhaohui, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China
  • Wu, Chia-Chao, Tri-Service General Hospital, Taipei, Taiwan
  • Jin, Kyubok, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
  • Kim, Yong-Lim, Kyungpook National University Hospital, Daegu, Korea (the Republic of)
  • Lu, Kuo-Cheng, Taipei Tzu Chi Hospital, Taipei, Taiwan
  • Chan, Tak Mao Daniel, The University of Hong Kong, Hong Kong, Hong Kong
  • Fukagawa, Masafumi, Tokai University School of Medicine, Isehara, Japan
  • Kinoshita, Jun, Kyowa Kirin Co., Ltd., Chiyoda-ku, Tokyo, Japan
  • Nagai, Chisato, Kyowa Kirin Co., Ltd., Chiyoda-ku, Tokyo, Japan
  • Kojima, Masahiro, Kyowa Kirin Co., Ltd., Chiyoda-ku, Tokyo, Japan
  • Yu, Xueqing, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China

Group or Team Name

  • the Orchestra Study Group
Background

Cinacalcet is widely used to control secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients, but its upper gastrointestinal (GI) side effects may lead to lower adherence and thus suboptimal efficacy. Evocalcet (KHK7580) is a new oral calcimimetic which can suppress intact parathyroid hormone (iPTH) while inducing fewer upper GI side effects. To date, the experience with evocalcet is only limited to Japanese patients. To compare its efficacy and safety against cinacalcet in SHPT patients of other Asian ethnicities, we conducted a Phase 3 study in Mainland China, Taiwan, Hong Kong and South Korea. (NCT03822507)

Methods

In this multicenter, randomized and double-blind trial, HD patients with SHPT and iPTH level >300 pg/mL were randomized to receive evocalcet (n=203) or cinacalcet treatment (n=201) for 52 weeks, at daily dose range of 1-12 mg and 25-100 mg respectively. The primary endpoint was the mean % change in iPTH level from baseline in Week 50-52. Incidence of pre-specified GI AEs (abdominal discomfort, nausea, vomiting, abdominal distension, and decreased appetite) was also evaluated.

Results

Evocalcet showed non-inferiority to cinacalcet. The difference in mean % change in iPTH level from baseline in evocalcet (–34.7%) and cinacalcet (–30.2%) was –4.4% (95% CI [–13.1, 4.3]; non-inferiority margin, +15%). The difference in proportion of participants with ≥30% decrease in iPTH from baseline between evocalcet (67.3%) and cinacalcet (58.7%) was 8.6% (95% CI [–1.8, 19.1]). Effective iPTH reduction from baseline was also observed in subjects with high baseline iPTH of ≥1000 pg/mL (–46.1% in evocalcet, –37.1% in cinacalcet). Upper GI AEs occurred in 33.5% of patients receiving evocalcet, which is significantly lower than 50.5% for cinacalcet (p=0.001). Meanwhile, incidences of pre-defined Calcium decrease-related AEs were similar in two groups (61.6% in evocalcet, 61.0% in cinacalcet).

Conclusion

In East Asian HD patients with SHPT, the efficacy of evocalcet in reducing serum iPTH is non-inferior to cinacalcet, and evocalcet showed significantly reduced GI side effects compared with cinacalcet. Evocalcet therefore presents a preferable treatment alternative to cinacalcet for SHPT.

Funding

  • Commercial Support