ECE2023 Rapid Communications Rapid Communications 8: Calcium and Bone (6 abstracts)
Treatment of chronic hypoparathyroidism by Eneboparatide, a novel PTH receptor-1 agonist: Results from a phase 2a study
Takács István 1 , Emese Mezozi 2 , Alfonso Soto 3 , Peter Kamenicky 4 , Lucile Figueres 5 , M. Angeles Galvez Moreno 6 , Sandrine Lemoine 7 , Françoise Borson-Chazot 8 , Ismael Capel 9 , Michel Ovize 10 , Taha OuldRouis 10 , Soraya Allas 10 , Mark Sumeray 10 & Michael Mannstadt 11
1Semmelweis Egyetem Belgyogyaszati es Hematologiai Klinika, Endocrinology, Budapest, Hungary; 2Pecsi Tudomanyegyetem, Endocrinology, Pecs, Hungary; 3Complejo Hospitalario Universitario A Coruña, Endocrinología y Nutrición, A Coruña, Spain; 4Hôpital Bicêtre AP-HP, Endocrinologie, Le Kre mlin-Bicêtre, France; 5Centre Hospitalier Universitaire Nantes – Hôtel Dieu, Néphrologie-immunologie clinique, Nantes, France; 6Hospital Universitario Reina Sofía, Endocrinología y Nutrición, Cordoba, Spain; 7Hôpital Edouard Herriot-HCL, Service de néphrologie et d’exploration fonctionnelle rénale, Lyon, France; 8Hospices Civils de Lyon – Hôpital Louis Pradel, Service d’endocrinologie, de diabétologie et des maladies métaboliques A, Bron, France; 9Hospital Parc Taulí de Sabadell, Servei d’Endocrinologia i Nutrició – Parc Taulí, Sabadell, Spain; 10Amolyt Pharma, Ecully, France; 11Massachusetts General Hospital and Harvard Medical School, Endocrine Unit, Boston, United States
Background: Conventional therapy for chronic hypoparathyroidism (cHP) is often unable to maintain stable normal serum calcium (Ca) levels for a full 24 h, to control symptoms, to prevent the detrimental long-term effects on the kidney and to preserve normal bone architecture. Eneboparatide (AZP-3601) is a novel 36-amino-acid peptide specifically designed to activate the R0 conformation of the PTH receptor 1, that results in a prolonged calcemic response and a sustained reabsorption of urinary calcium (uCa). We report the results of two consecutive cohorts (C1 and C2) of cHP patients enrolled in a phase 2 multi-center open-label study.
Methods: Patients conventional therapy was adjusted to have albumin-adjusted serum Ca (sCa) within the target range of 7.8 to 9.0 mg/dl before treatment with eneboparatide. From Day 1 onwards, patients received a daily sc. administration at a starting dose of 20 µg (C1; n=12) or 10µg eneboparatide/day (C2; n=16), while reducing oral Ca and active vitamin D (vitD) intake. Up-titration to a maximum of 60 µg (C1) or 80 µg/day (C2) was allowed. 24 hr-uCa, serum bone biomarkers (s-CTX and P1NP) were assessed. DXA scan was performed in C2.
Results: 24 patients (18 women), with a mean (SD) age of 56 (11) years and mostly post-surgery etiology were taking on average 0.61 (0.26) µg/day active vitD and 1733 (1442) mg oral Ca at baseline. Eneboparatide was well tolerated with no serious adverse events. In C2 the 10µg starting dose required an earlier up-titration to 20µg in most patients. After 3-month treatment with eneboparatide, 88% of patients were off active vitD and oral Ca supplements (≤500 mg/day) while mean sCa was maintained within the target range. Mean reduction in 24 hr-uCa from baseline after 3 months was 63% and 58%, in C1 and C2, respectively, including normalization in all 6 patients with hypercalciuria at baseline in C1 and 6 of 7 patients in C2. Bone biomarkers increased and remained within the normal range for the duration of the study, averaging 352 (166) and 477(252) ng/l for CTX (ULN=900 ng/l)) and 54(17) and 65(31) ng/l for P1NP (ULN=74 ng/l), in C1 and C2 at D84 respectively. In C2, BMD, T and Z scores did not significantly change at 3 months.
Conclusion: Eneboparatide allowed independence from conventional therapy and maintenance of sCa within a target range primarily via enhanced reabsorption of uCa while producing a balanced resumption of bone turnover. Data support advancement to Phase 3 and selection of 20µg as starting dose.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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