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Endocrine Abstracts (2023) 90 OC8.2 | DOI: 10.1530/endoabs.90.OC8.2

ECE2023 Oral Communications Oral Communications 8: Calcium and Bone (6 abstracts)

Eneboparatide, a Novel PTH-1 Receptor Agonist, Has No Impact on Bone Parameters Following Chronic Treatment of Non-Human Primates

Guillaume Ravel 1 , Thomas Delale 1 , Stéphane Milano 1 , Sophie Chirat 2 , Michael Verset 2 , Emilie Latronico 3 , Soraya Allas 1 & Michael D. Culler 4


1Amolyt Pharma, Ecully, France; 2Charles River Laboratories France, Saint Germain Nuelles, France; 3Voxcan, Dommartin, France; 4Amolyt Pharma, Cambridge, Massachusetts, United States

Eneboparatide (AZP-3601) is a novel, synthetic, 36-amino-acid peptide agonist of the parathyroid hormone type 1 receptor (PTHR1), with potent selectivity for the R0 conformation. This results in prolonged calcemic responses, while having a short circulating half-life. Eneboparatide is being developed for the treatment of chronic hypoparathyroidism (cHP). Studies in hypoparathyroid animal models and, most recently, in hypoparathyroid patients, have demonstrated that eneboparatide is effective in maintaining normal serum calcium in the absence of calcium/vitamin D supplementation and in normalizing urinary calcium excretion without deleterious impact on bone parameters. To further examine the effect of chronic eneboparatide treatment on bone, both 13-week and 39-week studies were conducted in non-human primates (NHP), which are considered a relevant species with regard to eneboparatide effects on serum calcium. Groups of 3 or 4 Cynomolgus monkeys of each sex were given daily subcutaneous injections of either vehicle or eneboparatide at doses of 1, 2.5 or 10 µg/kg for either 13 or 39 weeks. At the end of the 13-week study, right femur, right tibia and the L4 lumbar vertebra were collected from 3 animals/group/sex and bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. The left femur was submitted to histopathological examination. There was no evidence of any treatment-related effect on either BMD or histopathology. In the 39-week study, blood samples were collected from 4 animals/group/sex prior to and during weeks 4, 8, 13, 26 and 39 of treatment for measurement of bone biomarkers. In-life BMD of left femur, left tibia and L4 lumbar vertebra was measured by quantitative computed tomography prior to and during weeks 26 and 39 of treatment. At the end of the treatment period, femurs were processed for histopathological examination. Analysis of blood samples for the anabolic bone biomarker, N-terminal propeptide of type 1 procollagen (P1NP), and the catabolic bone biomarker, C-terminal telopeptide (CTX), revealed no treatment-related changes at any time in either sex. Prior to treatment, BMD was homogeneous among all groups for all the three bone sites examined. Over the course of the study, there were no statistically significant changes in BMD as compared to pre-treatment values, regardless of sex or eneboparatide treatment. Subsequent histological examination of the femur revealed no noteworthy findings. These results, demonstrating an absence of deleterious effect of chronic eneboparatide treatment on bone in NHP, further substantiate the potential of eneboparatide as an ideal treatment for hypoparathyroidism.

Volume 90

25th European Congress of Endocrinology

Istanbul, Turkey
13 May 2023 - 16 May 2023

European Society of Endocrinology 

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