ECE2023 Rapid Communications Rapid Communications 8: Calcium and Bone (6 abstracts)
Background: Conventional therapy with oral calcium (Ca) and active vitamin D (vitD) supplementation for chronic hypoparathyroidism (cHP) can induce or aggravate hypercalciuria and may lead to detrimental long-term renal complications. Eneboparatide (AZP-3601) is a novel 36-amino-acid peptide with a short half-life designed to activate the R0 conformation of the PTH 1 receptor which produces a prolonged calcemic response. This phase 2a study examined the effects of eneboparatide on urinary Ca (uCa) excretion in two consecutive cohorts (C1 and C2) of cHP patients.
Methods: Following an optimization period, during which Ca and active vitD doses were adjusted to achieve baseline albumin-adjusted serum calcium within the target range of 7.8 to 9.0 mg/dl, patients received a daily sc. injection of eneboparatide at initial doses of 20 µg/day (C1) or 10 µg/day (C2), while simultaneously reducing their Ca and active vitD intake. Subsequent up-titration to a maximum daily dose of 60 µg (C1) or 80 µg (C2) was allowed. Twenty-four-hour urinary Ca excretion (24 h-uCa), fractional excretion of Ca (FECa), 24 h-urinary phosphate (24 h-uP) and serum phosphate (sP) were assessed at baseline and at D84. Pooled data from 24 patients who completed the study are presented here.
Results: Twenty-four patients (18 women) aged (SD) 56 (11) years were taking 0.61 (0.26) µg/day active vitD and 1733(1442) mg oral Ca at baseline. At D84, active vitD and oral Ca were discontinued in 88% of patients, while mean albumin-adjusted serum calcium remained within the target range. Mean 24 h-uCa decreased from 325 (172) mg/24 h at baseline to 207 (107) mg/24 h and 130 (91) mg/24 h at D14 and D84, respectively. In 13 patients with hypercalciuria at baseline, we observed a 67% reduction of 24 h-uCa at D84 and a normalization of 24 h-uCa in 12 (92%). From baseline to D84, mean FECa decreased in the entire population and in patients with hypercalciuria. Between baseline and D84, 24 h-uP excretion increased from 721 (331) mg/24 h to 794 (238) mg/24 h while mean sP decreased from 4.3 (0.8) mg/dl to 3.7 (0.6) mg/dl.
Conclusion: These data demonstrate that eneboparatide treatment maintained sCa within the target range after withdrawal of conventional therapy, likely acting via a potent effect on the tubular reabsorption of calcium. The observed significant improvement in both uCa and sP is expected to translate to a clinically meaningful benefit for cHP patients in the long-term.
13 May 2023 - 16 May 2023