PMID- 38449442
OWN - NLM
STAT- Publisher
LR  - 20240307
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
DP  - 2024 Mar 6
TI  - An Open-Label Phase 2 Study of Eneboparatide, a Novel PTH Receptor 1 Agonist, in 
      Hypoparathyroidism.
LID - dgae121 [pii]
LID - 10.1210/clinem/dgae121 [doi]
AB  - CONTEXT: Hypoparathyroidism is a rare disorder characterized by a deficiency in 
      parathyroid hormone (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 20 microg/day (C1) or 10 microg/day (C2) starting dose. 
      Conventional therapy was progressively removed and eneboparatide could be 
      titrated up to 60 microg (C1) or 80 microg (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 (s-CTX and P1NP), 
      bone mineral density (BMD), and adverse events (AEs). RESULTS: After 3 months, 
       >/= 88% 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.
CI  - (c) 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.
FAU - Takacs, Istvan
AU  - Takacs I
AUID- ORCID: 0000-0002-7810-4833
AD  - Department of Internal Medicine and Oncology Semmelweis University, Budapest, 
      Hungary.
FAU - Mezosi, Emese
AU  - Mezosi E
AUID- ORCID: 0000-0001-9367-3877
AD  - Department of Endocrinology, Pecsi Tudomanyegyetem, Pecs, Hungary.
FAU - Soto, Alfonso
AU  - Soto A
AUID- ORCID: 0000-0001-6983-9320
AD  - Department of Endocrinology and Nutrition, Complejo Hospitalario Universitario A 
      Coruna, Coruna, Spain.
FAU - Kamenicky, Peter
AU  - Kamenicky P
AUID- ORCID: 0000-0002-1994-4226
AD  - Universite Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, 
      AP-HP, Hopital Bicetre, Service d'Endocrinologie et des Maladies de la 
      Reproduction, Centre de Reference des Maladies Rares du Metabolisme du Calcium et 
      du Phosphate, Le Kremlin Bicetre, France.
FAU - Figueres, Lucile
AU  - Figueres L
AUID- ORCID: 0000-0002-1473-2064
AD  - Department of Nephrology and Clinical Immunology, Centre Hospitalier 
      Universitaire Nantes-Universite de Nantes, Nantes, France.
FAU - Galvez Moreno, Maria Angeles
AU  - Galvez Moreno MA
AUID- ORCID: 0000-0001-6443-0227
AD  - Department of Endocrinology and Nutrition, Hospital Universitario Reina Sofia, 
      Cordoba, Spain.
FAU - Lemoine, Sandrine
AU  - Lemoine S
AUID- ORCID: 0000-0002-3460-2507
AD  - Department of Nephrologie, Hypertension-dialysis, Hospices Civils de Lyon and 
      Claude Bernard University, Lyon, France.
FAU - Borson-Chazot, Francoise
AU  - Borson-Chazot F
AUID- ORCID: 0000-0003-2515-7840
AD  - Department of Endocrinology, Diabetes and Metabolic Diseases, Hospices Civils de 
      Lyon and Claude Bernard University, Lyon, France.
FAU - Capel, Ismael
AU  - Capel I
AUID- ORCID: 0000-0003-2155-6764
AD  - Department of Endocrinology and Nutrition, Parc Tauli University Hospital, 
      Sabadell, Barcelona, Spain.
FAU - Ouldrouis, Taha
AU  - Ouldrouis T
AUID- ORCID: 0009-0002-0111-2234
AD  - Amolyt Pharma, Ecully, France.
FAU - Lucas, Nadege
AU  - Lucas N
AUID- ORCID: 0009-0002-3703-8937
AD  - Amolyt Pharma, Ecully, France.
FAU - Allas, Soraya
AU  - Allas S
AUID- ORCID: 0000-0002-3547-7883
AD  - Amolyt Pharma, Ecully, France.
FAU - Sumeray, Mark
AU  - Sumeray M
AUID- ORCID: 0009-0002-2870-0087
AD  - Amolyt Pharma, Ecully, France.
FAU - Ovize, Michel
AU  - Ovize M
AUID- ORCID: 0000-0002-2146-9874
AD  - Amolyt Pharma, Ecully, France.
FAU - Mannstadt, Michael
AU  - Mannstadt M
AUID- ORCID: 0000-0003-0867-9778
AD  - Endocrine Unit, Department of Medicine, Massachusetts General Hospital and 
      Harvard Medical School, Boston, MA, USA.
LA  - eng
PT  - Journal Article
DEP - 20240306
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
SB  - IM
OTO - NOTNLM
OT  - bone biomarkers
OT  - calcium
OT  - eneboparatide
OT  - hypoparathyroidism
OT  - parathyroid hormone
OT  - replacement therapy
EDAT- 2024/03/07 06:43
MHDA- 2024/03/07 06:43
CRDT- 2024/03/07 03:55
PHST- 2023/11/03 00:00 [received]
PHST- 2024/02/22 00:00 [revised]
PHST- 2024/02/27 00:00 [accepted]
PHST- 2024/03/07 06:43 [medline]
PHST- 2024/03/07 06:43 [pubmed]
PHST- 2024/03/07 03:55 [entrez]
AID - 7623629 [pii]
AID - 10.1210/clinem/dgae121 [doi]
PST - aheadofprint
SO  - J Clin Endocrinol Metab. 2024 Mar 6:dgae121. doi: 10.1210/clinem/dgae121.