Abstract：
BACKGROUND: Hypoparathyroidism is a rare disorder characterized by a deficiency in PTH resulting in hypocalcemia, hyperphosphatemia, and hypercalciuria. Eneboparatide is an investigational peptide agonist of the PTH1 receptor for the treatment of chronic hypoparathyroidism (HP).
OBJECTIVE: To evaluate the efficacy, safety, and tolerability of eneboparatide in HP patients.
METHODS: Open-label, phase 2 study.
METHODS: Twenty-eight patients (21 women, 7 men), mean age (range): 58 years (28-72), with HP were enrolled into 2 consecutive cohorts (C1, n = 12 and C2, n = 16).
METHODS: Following an optimization period, daily subcutaneous injections of eneboparatide were administered for 3 months at a 20 µg/day (C1) or 10 µg/day (C2) starting dose. Conventional therapy was progressively removed, and eneboparatide could be titrated up to 60 µg (C1) or 80 µg (C2).
RESULTS: Proportion of patients achieving independence from conventional therapy, albumin-adjusted serum calcium (ADsCa), 24-h urine calcium (uCa), serum bone turnover markers (serum carboxy-terminal telopeptide of type I collagen and procollagen 1 intact N-terminal propeptide), bone mineral density (BMD), and adverse events (AEs).
RESULTS: After 3 months, ≥ 88% of patients achieved independence from conventional therapy while mean ADsCa was maintained within target range (7.8-9 mg/dL). Eneboparatide induced a rapid and sustained reduction of mean 24-hour uCa, even among patients with hypercalciuria. Bone turnover markers slightly increased, and BMD remained unchanged, consistent with progressive resumption of physiologic bone turnover. Eneboparatide was well tolerated with no serious AEs.
CONCLUSIONS: Eneboparatide allowed independence from conventional therapy and maintenance of serum calcium within a target range while normalizing uCa excretion and producing a balanced resumption of bone turnover.
OBJECTIVE: To evaluate the efficacy, safety, and tolerability of eneboparatide in HP patients.
METHODS: Open-label, phase 2 study.
METHODS: Twenty-eight patients (21 women, 7 men), mean age (range): 58 years (28-72), with HP were enrolled into 2 consecutive cohorts (C1, n = 12 and C2, n = 16).
METHODS: Following an optimization period, daily subcutaneous injections of eneboparatide were administered for 3 months at a 20 µg/day (C1) or 10 µg/day (C2) starting dose. Conventional therapy was progressively removed, and eneboparatide could be titrated up to 60 µg (C1) or 80 µg (C2).
RESULTS: Proportion of patients achieving independence from conventional therapy, albumin-adjusted serum calcium (ADsCa), 24-h urine calcium (uCa), serum bone turnover markers (serum carboxy-terminal telopeptide of type I collagen and procollagen 1 intact N-terminal propeptide), bone mineral density (BMD), and adverse events (AEs).
RESULTS: After 3 months, ≥ 88% of patients achieved independence from conventional therapy while mean ADsCa was maintained within target range (7.8-9 mg/dL). Eneboparatide induced a rapid and sustained reduction of mean 24-hour uCa, even among patients with hypercalciuria. Bone turnover markers slightly increased, and BMD remained unchanged, consistent with progressive resumption of physiologic bone turnover. Eneboparatide was well tolerated with no serious AEs.
CONCLUSIONS: Eneboparatide allowed independence from conventional therapy and maintenance of serum calcium within a target range while normalizing uCa excretion and producing a balanced resumption of bone turnover.
摘要：
背景：甲状旁腺功能减退症是一种罕见的疾病，其特征是甲状旁腺激素（PTH）缺乏导致低钙血症，高磷酸盐血症,和高钙尿症。内布帕拉肽是用于治疗慢性甲状旁腺功能减退症（HP）的PTH1受体的研究性肽激动剂。
目的：为了评估疗效，安全,和依奈布帕拉肽在HP患者中的耐受性。
方法：开放标签，第二阶段研究。
方法：28名患者（21名女性，7名男子），平均年龄（范围）：58岁（28-72岁），HP患者被纳入2个连续队列(C1,n=12,和C2,n=16).
方法：经过优化后，每日皮下注射依奈布帕拉肽,起始剂量为20µg/天(C1)或10µg/天(C2),共3个月.逐渐取消常规治疗，恩贝帕拉肽可滴定至60µg（C1）或80µg（C2）。
结果：实现独立于常规治疗的患者比例，白蛋白调节血清钙（ADsCa），24小时尿钙（uCa），血清骨转换标志物（s-CTX和P1NP），骨矿物质密度（BMD），和不良事件（AE）。
结果：3个月后，≥88％的患者实现了与常规治疗的独立性，而平均ADsCa维持在目标范围内（7.8-9mg/dL）。依奈帕拉肽诱导平均24小时uCa的快速和持续降低，甚至在高钙尿症患者中。骨转换标志物略有增加，BMD保持不变，与生理骨转换的进行性恢复一致。依奈布帕拉肽耐受性良好，无严重不良事件发生。
结论：依奈帕拉肽允许独立于常规治疗，并将血清钙维持在目标范围内，同时使uCa排泄正常化并产生骨转换的平衡恢复。
目的：为了评估疗效，安全,和依奈布帕拉肽在HP患者中的耐受性。
方法：开放标签，第二阶段研究。
方法：28名患者（21名女性，7名男子），平均年龄（范围）：58岁（28-72岁），HP患者被纳入2个连续队列(C1,n=12,和C2,n=16).
方法：经过优化后，每日皮下注射依奈布帕拉肽,起始剂量为20µg/天(C1)或10µg/天(C2),共3个月.逐渐取消常规治疗，恩贝帕拉肽可滴定至60µg（C1）或80µg（C2）。
结果：实现独立于常规治疗的患者比例，白蛋白调节血清钙（ADsCa），24小时尿钙（uCa），血清骨转换标志物（s-CTX和P1NP），骨矿物质密度（BMD），和不良事件（AE）。
结果：3个月后，≥88％的患者实现了与常规治疗的独立性，而平均ADsCa维持在目标范围内（7.8-9mg/dL）。依奈帕拉肽诱导平均24小时uCa的快速和持续降低，甚至在高钙尿症患者中。骨转换标志物略有增加，BMD保持不变，与生理骨转换的进行性恢复一致。依奈布帕拉肽耐受性良好，无严重不良事件发生。
结论：依奈帕拉肽允许独立于常规治疗，并将血清钙维持在目标范围内，同时使uCa排泄正常化并产生骨转换的平衡恢复。
