Comparison of the Oral Calcimimetics Evocalcet and Cinacalcet in East Asian Patients on Hemodialysis with Secondary Hyperparathyroidism

Abstract

Introduction: Evocalcet is an oral calcimimetic agent with proven efficacy and safety in treating secondary hyperparathyroidism (SHPT) in Japanese patients on dialysis.

Methods: This randomized, double-blind, intrapatient dose-adjustment, parallel-group, international multicenter study compared the efficacy and safety of evocalcet versus cinacalcet for 52 weeks in East Asian hemodialysis patients with SHPT.

Results: In total, 203 and 200 patients were randomized to receive evocalcet or cinacalcet, respectively (overall, 70.1% had baseline intact parathyroid hormone (PTH) levels ≥500 pg/ml, with no between-group difference). Mean percentage changes in intact PTH levels from baseline were -34.7% and -30.2% in the evocalcet and cinacalcet groups at 52 weeks (between-group difference -4.4%, 95% confidence interval [CI] -13.1%, 4.3%, below the predefined 15% noninferiority margin). Overall, 67.3% and 58.7% of patients in the evocalcet and cinacalcet groups, respectively, achieved ≥30% decrease in intact PTH levels from baseline (between-group difference 8.6%; 95% CI -1.8%, 19.1%). No major safety concerns were observed. Gastrointestinal adverse events (AEs) were significantly less frequent with evocalcet compared with cinacalcet (33.5% vs. 50.5%, P = 0.001), whereas the incidence of hypocalcemia did not differ.

Conclusion: Evocalcet might be a better alternative to cinacalcet for East Asian patients on hemodialysis with SHPT.

Keywords: East Asia; cinacalcet; evocalcet; gastrointestinal; randomized controlled trial; secondary hyperparathyroidism.

Graphical abstract

Figure 1

Study design. ^aThe screening assessments were conducted within 30 days prior to the first dose of study drug.

Figure 2

Patient disposition. TEAE, treatment-emergent adverse event.

Figure 3

Time course of (a) iPTH (Median [Q1–Q3]), (b) corrected serum Ca (Mean + SD), and (c) serum P levels (Mean + SD) during the study in the FAS. Ca, calcium; FAS, full analysis set; P, phosphorus; PTH, parathyroid hormone; Q, quartile.

Figure 4

Forest plot quantifying the risk difference of GI-related AEs by treatment group. For the evocalcet group, the 95% CIs were calculated using the Clopper–Pearson method. For the cinacalcet group, 95% CIs were calculated using the Wald test method. The p-value was based on Fisher’s exact test. MedDRA Version 24.0 was used to code AEs. A patient was counted only once per AE category and once per unique PT within the AE category. AE, adverse event; CI, confidence interval; GI, gastrointestinal; PT, preferred term; SAF, safety analysis set.