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Publications

Journal Article Ahead of print

PubMed: 42166177 DOI: 10.1093/jbmr/zjag085

Sustained Improvement in Renal Function with Palopegteriparatide in Adults with Chronic Hypoparathyroidism: 2-Year Results from the Phase 3 PaTHway-Trial.

J Bone Miner Res

Authors: Lars Rejnmark, Elvira O Gosmanova, Aliya A Khan, Stuart Sprague, Dolores M Shoback, Lynn Kohlmeier, Mishaela R Rubin, Andrea Palermo, Peter Schwarz, Claudia Gagnon, Elena Tsourdi, Yasuhiro Takeuchi, Noriko Makita, Yasuo Imanishi, Neil Gittoes, Juan J Díez, Caroline Prot-Bertoye, Bryant Lai, Carol Zhao, Jenny Ukena, Michael A Makara, Christopher T Sibley, Aimee D Shu

Affiliations

  • Aarhus University Hospital, Clinical Medicine and Endocrinology, Aarhus, Denmark.
  • Albany Stratton VA Medical Center Albany, Nephrology Section, Department of Medicine, Albany, NY, US.
  • Albany Medical College, Albany, NY, US.
  • McMaster University Department of Medicine, Divisions Endocrinology and Metabolism and Geriatrics, Hamilton, ON, CA.
  • NorthShore University Health System, Chicago, IL, US.
  • University of Chicago Pritzker School of Medicine, Chicago, IL, USA.
  • University of California San Francisco Medical Center, Endocrine Research Unit.
  • San Francisco VA Medical Center, San Francisco, CA, USA.
  • Endocrinology and Spokane Osteoporosis, Spokane, WA, USA.
  • Columbia University, New York, NY, USA.
  • Campus Bio-Medico University, Endocrinology and Diabetes, Roma, Italy.
  • Rigshospitalet, Department of Endocrinology, Copenhagen, Denmark.
  • Université Laval Faculté de médecine, Medicine, Quebec, QC, CA.
  • Centre de recherche du CHU de Québec-Université Laval, Quebec, QC, CA.
  • Dresden University of Technology, Department of Medicine III & Center for Healthy Aging, Dresden, DE.
  • Toranomon Hospital Kajigaya, Kawasaki, Kanagawa Prefecture, JP.
  • Okinaka Memorial Institute for Medical Research, Minato, Tokyo, JP.
  • The University of Tokyo Hospital, Division of Nephrology and Endocrinology, Tokyo, JP.
  • Osaka Metropolitan University Graduate School of Medicine, Department of Clinical Medical Science, Osaka, Osaka Prefecture, JP.
  • Queen Elizabeth Hospital Birmingham, Centre for Endocrinology, Diabetes and MetabolismBirmingham, Birmingham, UK.
  • Hospital Universitario Puerta de Hierro Majadahonda, Department of Endocrinology, Majadahonda, ES.
  • Hôpital Européen Georges Pompidou, Service de Physiologie-Explorations Fonctionnelles, Paris, FR.
  • Assistance Publique Hôpitaux de Paris, Centre de Référence des Maladies Rares du Calcium et du Phosphate, Paris, FR.
  • Université Paris Cité, Paris, FR.
  • Ascendis Pharma, LLC, Palo Alto, CA, USA.

Abstract

The PaTHway clinical trial demonstrated sustained efficacy, safety, and tolerability of daily palopegteriparatide in the treatment of adults with hypoparathyroidism. Palopegteriparatide treatment was also associated with improvements in eGFR over 52 weeks in a post hoc analysis, prompting further exploration of palopegteriparatide in the preservation of renal function. The current post hoc analysis evaluated the impact of palopegteriparatide treatment on renal function in adults with hypoparathyroidism through Week 104; as with prior analysis, changes in renal function were assessed using eGFR. At Week 104, 93% (76/82) of participants remained in the open-label extension. Of those, 82% had albumin-adjusted serum calcium levels in the normal range (8.3-10.6 mg/dL), 97% were independent from conventional therapy (≤ 600 mg/day of elemental calcium and no active vitamin D). Mean (SD) serum phosphate (3.5 (0.7) mg/dL) and albumin-adjusted calcium x phosphate product (30.7(5.1) mg2/dL2) levels were also within normal ranges. Palopegteriparatide treatment resulted in a mean (SD) increase in eGFR of 8.9 (11.0) mL/min/1.73m2 (P<0.0001) from baseline to Week 52, which was sustained through Week 104, where it was 77.8 (14.8) mL/min/1,73m2 with a mean (SD) change from baseline of 9.0 (10.3) mL/min/1.73 m2 (P < 0.0001). By Week 104, 45% and 34% of participants had an increase in eGFR of ≥ 5 mL/min/1.73 m2 and ≥ 10 mL/min/1.73 m2, respectively. Palopegteriparatide treatment normalized mean (SD) 24-hour urine calcium within 26 weeks and maintained levels below 250 mg/day through Week 104 (158.8 (90.5) mg/24 h). Most treatment-emergent adverse events were mild or moderate; no new safety signals or cases of treatment-related nephrolithiasis were reported. These findings demonstrate sustained renal safety of palopegteriparatide and suggest that PTH replacement therapy with palopegteriparatide preserves and may improve renal function in adults with chronic hypoparathyroidism after 104 weeks of treatment.

MeSH

Hypoparathyroidism, Safety, Serum, Calcium, Therapeutics