Evocalcet in patients with primary hyperparathyroidism: an open-label, single-arm, multicenter, 52-week,...

Primary hyperparathyroidism (PHPT) is caused by parathyroid adenoma, primary parathyroid hyperplasia, or parathyroid carcinoma. For some patients with PHPT controlling serum calcium levels is critical.

We conducted an open-label, single-arm, 52-week, phase III study in Japanese patients with hypercalcemia due to PHPT to demonstrate efficacy and safety of evocalcet, a new calcimimetic. Patients with intractable PHPT (n = 13), postsurgical recurrence (n = 2), and parathyroid carcinoma (n = 3) were enrolled. Evocalcet administration started at a dose of 2 mg once or twice daily and was titrated to achieve the target serum corrected calcium (cCa) concentration (≤ 10.3 mg/dL) for two consecutive weeks (maximal dose 24 mg/day).

Fourteen patients achieved the target (77.8%; 95% confidence interval [CI] 52.4-93.6). The lower limit of 95% CI exceeded the predetermined reference limit (11%), and thus, efficacy was confirmed. Of 18 patients, 12 (66.7%; 95% CI 41.0-86.7) showed decreased serum cCa of ≥ 1.0 mg/dL from the baseline for two consecutive weeks during the titration phase. Sixteen patients entered the maintenance phase, and 15 patients completed the study. Treatment-emergent adverse events (TEAEs) were recorded in 18/18 patients (100%) and drug-related TEAEs in 8/18 (44.4%). The most commonly observed drug-related TEAE was nausea (2/18 patients). No unexpected drug-related TEAEs were observed. All drug-related TEAEs were mild in severity. No patient discontinued the study because of drug-related TEAEs.

Evocalcet demonstrated long-term effectiveness in reducing serum cCa concentrations and safety without any unexpected drug-related TEAEs in PHPT patients.