Kidney Week

Abstract: TH-PO0227

Sustained Improvement in Kidney Function with Palopegteriparatide in Adults with Chronic Hypoparathyroidism: Three-Year Results from the PaTH Forward and PaTHway Trials

Session Information

• Bone and Mineral Metabolism: Clinical Reports and Practice
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 502 Bone and Mineral Metabolism: Clinical

Authors

• Gosmanova, Elvira O., Albany Medical College, Albany, New York, United States

Elvira O. Gosmanova, MD, FASN

• Schwarz, Peter, Rigshospitalet, Copenhagen, Capital Region of Denmark, Denmark

Peter Schwarz, DrMed

• Rejnmark, Lars, Aarhus Universitetshospital, Aarhus, Central Denmark Region , Denmark

Lars Rejnmark, MD, DrMed, PhD

• Khan, Aliya Aziz, McMaster University, Hamilton, Ontario, Canada

Aliya Aziz Khan, MD

• Clarke, Bart L., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Bart L. Clarke, MD

• Cetani, Filomena, Universita degli Studi di Pisa, Pisa, Tuscany, Italy

Filomena Cetani, MD, PhD

• Sprague, Stuart Michael, Endeavor Health, Evanston, Illinois, United States

Stuart Michael Sprague, DO

• Shoback, Dolores, University of California San Francisco, San Francisco, California, United States

Dolores Shoback, MD

• Kohlmeier, Lynn, Spokane Osteoporosis and Endocrinology, Spokane, Washington, United States

Lynn Kohlmeier, MD

• Rubin, Mishaela, Columbia University, New York, New York, United States

Mishaela Rubin, MD, MS

• Palermo, Andrea, Fondazione Policlinico Campus Bio-medico and Unit of Endocrinology and Diabetes, Rome, Italy

Andrea Palermo, MD, PhD

• Gagnon, Claudia, Universite Laval Faculte de Medecine, Québec City, Quebec, Canada

Claudia Gagnon

• Tsourdi, Elena, Technische Universität Dresden Medical Center, Dresden, Germany

Elena Tsourdi, MD, PhD

• Zhao, Carol, Ascendis Pharma Inc, Palo Alto, California, United States

Carol Zhao

• Makara, Michael A., Ascendis Pharma Inc, Palo Alto, California, United States

Michael A. Makara, PhD

• Lai, Bryant, Ascendis Pharma Inc, Palo Alto, California, United States

Bryant Lai, PharmD

• Ukena, Jenny, Ascendis Pharma Inc, Palo Alto, California, United States

Jenny Ukena, MD

• Sibley, Christopher T, Ascendis Pharma Inc, Palo Alto, California, United States

Christopher T Sibley, MD

• Shu, Aimee D., Ascendis Pharma Inc, Palo Alto, California, United States

Aimee D. Shu, MD

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 in adults for the treatment of chronic hypoparathyroidism. Conventional therapy for hypoparathyroidism (active vitamin D and calcium) is associated with hypercalciuria and an increased risk of CKD in these individuals. Rapid improvement in renal function after palopegteriparatide treatment initiation has been reported previously; this analysis evaluated the long-term impact of palopegteriparatide on renal function.

Methods

Three-year data were analyzed post-hoc from the phase 2 PaTH Forward and phase 3 PaTHway trials, comprising randomized, double-blind, placebo-controlled periods through Weeks 4 and 26 and open-label extension periods through Weeks 266 and 182, respectively. Renal function was assessed by eGFR. eGFR ≥30 mL/min/1.73 m² was required for eligibility. Safety assessments included 24-hour urine calcium excretion and treatment-emergent adverse events (TEAEs).

Results

At Year 3, ≥91% of participants receiving palopegteriparatide in both trials were independent from conventional therapy (no active vitamin D and ≤600 mg/day elemental calcium) and ≥84% had normocalcemia (8.3-10.6 mg/dL). Mean (SD) eGFR increased from baseline to Year 3 by 9.8 (10.9) mL/min/1.73 m² in PaTH Forward and by 8.8 (11.9) mL/min/1.73 m² in PaTHway. eGFR slope had an initial increase from baseline to 26 weeks (12.5 and 15.6 mL/min/1.73m²/year, annualized) followed by chronic slope stabilization from week 26 to Year 3 (0.6 and 1.2 mL/min/1.73 m²/year). Mean 24-hour urine calcium levels normalized (≤250 mg/day), decreasing from baseline to Year 3 (428.0 to 174.4 mg/day, PaTH Forward; 375.6 to 162.1 mg/day, PaTHway). Most TEAEs were grade 1 or 2, with no new safety signals identified.

Conclusion

Palopegteriparatide treatment showed sustained improvement in renal function, resolution of hypercalciuria, and continued safety and efficacy through Year 3 of PaTH Forward and PaTHway.

Funding

• Commercial Support – Ascendis Pharma Bone Diseases A/S

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20253yamgex4