ECEESPE2025 Oral Communications Oral Communications 7: Bone and Mineral Metabolism (9 abstracts)
Long-term efficacy and safety of palopegteriparatide treatment in adults with chronic hypoparathyroidism: 4-year results from the phase 2 path forward trial
Andrea Palermo 1 , Aliya Khan 2 , Mishaela Rubin 3 , Peter Schwarz 4 , Bart L. Clarke 5 , Uberto Pagotto 6 , Elena Tsourdi 7 , Filomena Cetani 8 , Rajesh Jain 9 , Carol Zhao 10 , Michael Ominsky 10 , Bryant Lai 10 , Jenny Ukena 10 , Christopher Sibley 10 , Aimee Shu 10 & Lars Rejnmark 11
1Unit of Metabolic Bone and Thyroid Disorders, Fondazione Policlinico Campus Bio-medico, Rome, Italy and Unit of Endocrinology and Diabetes, Campus Bio-medico University, Rome, Italy; 2McMaster University, Hamilton, Canada; 3Columbia University, New York, United States; 4Rigshospitalet, Copenhagen, Denmark; 5Mayo Clinic, Rochester, United States; 6Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy; 7Technische Universität Dresden Medical Center, Dresden, Germany; 8University of Pisa, Department of Clinical and Experimental Medicine, Endocrine Unit, Pisa, Italy; 9University of Chicago, Chicago, United States; 10Ascendis Pharma Inc, Palo Alto, United States; 11Aarhus University Hospital, Aarhus N, Denmark
JOINT1232
Background: Hypoparathyroidism is an endocrine disease caused by insufficient levels of parathyroid hormone (PTH). Conventional therapy for hypoparathyroidism (active vitamin D, elemental calcium) aims to alleviate hypocalcemia but does not address insufficient PTH. Palopegteriparatide is a prodrug of PTH (1-34), administered once daily, designed to provide active PTH within the physiological range for 24 hours/day in adults with chronic hypoparathyroidism. It is approved by the EC, MHRA, and FDA. This analysis investigated the long-term efficacy and safety of palopegteriparatide in adults with chronic hypoparathyroidism through week 214 of the PaTH Forward trial.
Methods: PaTH Forward is a phase 2 trial with a 4-week randomized, double-blind, placebo-controlled period, followed by an ongoing open-label extension period. Renal function was assessed by estimated glomerular filtration rate (eGFR). Bone turnover markers C-terminal telopeptide of type 1 collagen (CTx) and procollagen type 1 N-terminal propeptide (P1NP), and bone mineral density (BMD) measured by DXA, were assessed at baseline and regular intervals through week 214. Safety assessments included 24-hour urine calcium and treatment-emergent adverse events (TEAEs).
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 normal albumin-adjusted serum calcium levels (2.07-2.64 mmol/l) with a mean (SD) of 2.24 (0.10) mmol/l. Mean CTx and P1NP increased from the low end of normal at baseline, peaked by week 26, and declined thereafter and remained stable above baseline levels through week 214. The elevated baseline mean BMD Z-scores trended towards age- and sex-matched norms at the lumbar spine, femoral neck, and total hip and largely stabilized after 26 weeks of treatment, remaining above zero through week 214. Changes in Z-scores were larger in participants with longer duration of hypoparathyroidism but were similar across the population when considering sex and age/menopausal status. Mean (SD) eGFR at week 214 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 treatment, remaining below the upper limit of normal (≤6.2 mmol/day) through week 214 (4.4 [2.1] mmol/day). TEAEs were mostly mild or 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 the PaTH Forward trial, highlighting continued benefits in skeletal dynamics and renal function.
Volume 110
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Endocrine Abstracts
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