An Open-label Phase 2 Study of Eneboparatide, a Novel PTH Receptor 1 Agonist, in Hypoparathyroidism.

Autor:	Takacs I; Department of Internal Medicine and Oncology, Semmelweis University, 1088 Budapest, Hungary., Mezosi E; Department of Endocrinology, Pecsi Tudomanyegyetem, 7623 Pecs, Hungary., Soto A; Department of Endocrinology and Nutrition, Complejo Hospitalario Universitario A Coruña, 15006 Coruña, Spain., Kamenický P; Physiologie et Physiopathologie Endocriniennes, AP-HP, Hôpital Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphate, Université Paris-Saclay, Inserm, 94270 Le Kremlin Bicêtre, France., Figueres L; Department of Nephrology and Clinical Immunology, Centre Hospitalier Universitaire Nantes-Université de Nantes, 44093 Nantes, France., Galvez Moreno MA; Department of Endocrinology and Nutrition, Hospital Universitario Reina Sofía, 14004 Cordoba, Spain., Lemoine S; Department of Nephrologie, Hypertension-dialysis, Hospices Civils de Lyon and Claude Bernard University, 69008 Lyon, France., Borson-Chazot F; Department of Endocrinology, Diabetes and Metabolic Diseases, Hospices Civils de Lyon and Claude Bernard University, 69394 Lyon, France., Capel I; Department of Endocrinology and Nutrition, Parc Tauli University Hospital, 08208 Sabadell, Barcelona, Spain., Ouldrouis T; Amolyt Pharma, 69130 Ecully, France., Lucas N; Amolyt Pharma, 69130 Ecully, France., Allas S; Amolyt Pharma, 69130 Ecully, France., Sumeray M; Amolyt Pharma, 69130 Ecully, France., Ovize M; Amolyt Pharma, 69130 Ecully, France., Mannstadt M; Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2024 Aug 13; Vol. 109 (9), pp. 2199-2209.
DOI:	10.1210/clinem/dgae121
Abstrakt:	Context: 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. Design: Open-label, phase 2 study. Participants: 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). Intervention: 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). Main Outcomes: 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. Conclusion: 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. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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