Long-Term Efficacy and Safety of Palopegteriparatide Treatment in Adults With Chronic Hypoparathyroidism: 4-Year Results From the Phase 2 PaTH Forward Trial

Neil Gittoes; Andrea Palermo; Aliya Khan; Mishaela Rubin; Peter Schwarz; Bart Clarke; Uberto Pagotto; Elena Tsourdi; Filomena Cetani; Rajesh Jain; Carol Zhao; Michael Ominsky; Bryant Lai; Jenny Ukena; Christopher Sibley; Aimee Shu; Lars Rejnmark

doi:10.1530/endoabs.117.P57

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Endocrine Abstracts (2026) 117 P57 | DOI: 10.1530/endoabs.117.P57

SFEBES2026 Poster Presentations Bone and Calcium (28 abstracts)

Long-Term Efficacy and Safety of Palopegteriparatide Treatment in Adults With Chronic Hypoparathyroidism: 4-Year Results From the Phase 2 PaTH Forward Trial

Neil Gittoes ¹ , Andrea Palermo ^2,3 , Aliya Khan ⁴ , Mishaela Rubin ⁵ , Peter Schwarz ⁶ , Bart Clarke ⁷ , Uberto Pagotto ^8,9 , Elena Tsourdi ¹⁰ , Filomena Cetani ¹¹ , Rajesh Jain ¹² , Carol Zhao ¹³ , Michael Ominsky ¹³ , Bryant Lai ¹³ , Jenny Ukena ¹³ , Christopher Sibley ¹³ , Aimee Shu ¹³ & Lars Rejnmark ¹⁴

Author affiliations

¹Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham and Queen Elizabeth Hospital, Birmingham, United Kingdom; ²Unit of Metabolic Bone and Thyroid Disorders, Fondazione Policlinico Campus Bio-medico, Rome, Italy; ³Unit of Endocrinology and Diabetes, Campus Bio-medico University, Rome, Italy; ⁴McMaster University, Hamilton, Canada; ⁵Columbia University, New York, USA; ⁶Rigshospitalet, Copenhagen, Denmark; ⁷Mayo Clinic, Rochester, USA; ⁸Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; ⁹Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy; ¹⁰Technische Universität Dresden Medical Center, Dresden, Germany; ¹¹University of Pisa, Department of Clinical and Experimental Medicine, Endocrine Unit, Pisa, Italy; ¹²University of Chicago, Chicago, USA; ¹³Ascendis Pharma Inc, Palo Alto, USA; ¹⁴Aarhus University Hospital, Aarhus N, Denmark

Background: Palopegteriparatide is a prodrug of PTH (1-34), administered once daily, designed to provide active PTH within the physiological range for 24 hours/day. It is approved in the US, EU, UK and several other countries.

Methods: This analysis investigated the efficacy and safety of palopegteriparatide in adults with chronic hypoparathyroidism through week 214 of PaTH Forward, a phase 2 trial with a 4-week randomized, double-blind, placebo-controlled period, followed by open-label extension through week 266.

Results: At week 214, 95% (56/59) of participants remained in the trial; of those, 93% were independent from conventional therapy (no active vitamin D and ≤600 mg/day elemental calcium) and 98% had normocalcemia (2.07-2.64 mmol/l). Mean bone turnover markers C-terminal telopeptide of type 1 collagen (CTx) and procollagen type 1 N-terminal propeptide (P1NP) increased from low end of normal at baseline, peaked by week 26, and declined thereafter, remaining stable above baseline. Elevated baseline mean BMD Z-scores trended towards age- and sex-matched norms at lumbar spine, femoral neck, and total hip, largely stabilized after week 26 and remained above zero. At week 214, mean (SD) eGFR was 86.0 (21.7) mL/min/1.73 m², reflecting a mean (SD) increase of 7.6 (13.7) mL/min/1.73 m² from baseline. Mean (SD) 24-hour urine calcium levels normalized with palopegteriparatide and were maintained (≤6.2 mmol/day). TEAEs were mostly mild/moderate; no new safety signals were identified.

Conclusion: These results demonstrate sustained efficacy and safety of palopegteriparatide in adults with chronic hypoparathyroidism through week 214 of PaTH Forward, suggesting continued benefits in skeletal dynamics and renal function.