OR23-04 Treatment Of Chronic Hypoparathyroidism With Eneboparatide (AZP-3601), A Novel PTH 1 Receptor Agonist: Results From A Phase 2 Trial

Abstract

Abstract Disclosure: P. Kamenicky: Consulting Fee; Self; consultant. I. Takacs: Consulting Fee; Self; consultant. E. Mezosi: None. A. Soto: None. L. Figueres: None. S. Lemoine: None. F. Borson-Chazot: None. I. Capel: None. M.A. Galvez moreno: None. M. Ovize: Employee; Self; employee. T. OuldRouis: Employee; Self; employee. S. allas: Employee; Self; employee. M. Sumeray: Employee; Self; employee. M. Mannstadt: Consulting Fee; Self; consultant. Background: Conventional therapy for chronic hypoparathyroidism (cHP) is often unable to maintain normal serum calcium levels throughout the day, control symptoms, or prevent hypercalciuria and long-term renal complications. Eneboparatide is a novel 36-amino-acid peptide designed to activate the R0 conformation of the PTH 1 receptor, which produces a prolonged calcemic response despite a short half-life. We previously presented data from the first cohort (n=10) and report here the results of the second cohort of cHP patients enrolled in our phase 2 multi-center study. Methods: Before starting Eneboparatide treatment, all patients received oral calcium (Ca) and active vitamin D (vitD) adjusted to achieve albumin-adjusted serum Ca (sCa) levels within the target range of 7.8 mg/dL to 9.0 mg/dL. Starting Day 1, patients received a once-daily sc. injection of Eneboparatide, while simultaneously reducing their Ca and active vitD intake. The initial dose of 10 µg/day(d) could be titrated up to 80 µg/d. sCa, urinary excretion of calcium (24h-uCa) and serum bone biomarkers (s-CTX and P1NP) were assessed. DXA was performed at baseline and at D84. Results: Fourteen patients (10 women), with a mean (SD) age of 52 (11) years,79% post-surgical, were taking an average of 0.58 (0.25) µg/d calcitriol and 1786 (1800) mg/d oral Ca at baseline. Eneboparatide was well tolerated with no serious adverse event. At 3 months, over 90% of patients were off active vitD and oral Ca (≤500mg/d). In 13 of 14 patients, Eneboparatide was up-titrated early and the dose averaged 43(18) µg/d at D84 while sCa was 8.32 (0.72) mg/dL. Six of 14 patients displayed osteopenia or osteoporosis at least on one site at baseline. BMD, T and Z scores did not significantly change after 3 months. In 7 patients with hypercalciuria at baseline, mean 24h-uCa decreased by 49% at D14 and was normal in 6 of 7 patients at D84. Mean s-CTX and P1NP levels increased progressively from 217 (113) and 38 (13) at baseline to 477 (252) ng/L and 65 (31) ng/L at D84, respectively (all within the normal range). Conclusion: These results demonstrate that Eneboparatide treatment was safe and allowed independence from conventional therapy while maintaining mean sCa within the target range. Eneboparatide had a strong effect on renal reabsorption of calcium but limited effects on bone turnover. These data and the results from our first cohort support the advancement of Eneboparatide to Phase 3 and selection of 20 µg/d as a starting dose. Presentation: Saturday, June 17, 2023