Palopegteriparatide Provides Sustained Response in Adults with Hypoparathyroidism

Results from a 3-year phase 3 trial have indicated a sustained response to palopegteriparatide (TransCon PTH) therapy in adults with hypoparathyroidism.1

Announced by Ascendis Pharma on July 14, 2025, palopegteriparatide continued to provide durable responses in adults with hypoparathyroidism, regardless of whether it was post-surgical, autoimmune, genetic, or idiopathic. Biochemistries, kidney function, and quality of life were all significantly improved.1

Hypoparathyroidism, a rare endocrine disease caused by insufficient levels of parathyroid hormone (PTH), the main regulator of phosphate and calcium balance. The disease acts directly on bones and the kidney and indirectly on the intestine. Several short-term and long-term complications, such as neuromuscular irritability, renal complications, extra-skeletal calcifications, and cognitive impairment, have been associated with hypoparathyroidism. Post-surgical hypothyroidism accounts for 70-80% of cases.1

“We are pleased to report these latest data from our second clinical trial of TransCon PTH showing sustained efficacy and improvements across key health and quality of life measures, beginning at the earliest timepoints in the Phase 3 PaTHway trial and continuing through three years of treatment,” said Aimee Shu, MD, executive vixce president of Endocrine & Rare Disease Medical Science and chief medical officer at Ascendis Pharma. “These responses, including normalization of skeletal dynamics with significant and clinically meaningful improvements in kidney function, demonstrate the long-term benefits of this treatment option for the vast majority of adults with hypoparathyroidism, regardless of their disease etiology.”1

The new data comes from Week 156 of the Phase 3 randomized, double-blind, placebo-controlled PaTHway trial, which consisted of a 26-week trial of 82 adults with chronic hypoparathyroidism followed by an open-label extension period through Week 182. The initial 26-week blinded period saw patients randomized in a 3:1 ratio to either palopegteriparatide or placebo. Investigators assessed their renal function by estimated glomerular filtration rate (eGFR). Safety assessments included 24-hour urine-calcium and treatment-emergent adverse events (TEAEs).1

Hypoparathyroidism symptoms, as well as functioning and well-being, were measured via the Hypoparathyroidism Patient Experience Scale (HPES). The trial exhibited a high retention rate, with 73 of the initial 82 patients (89%) completing the full trial.1

At the end of Week 156, a total of 64 participants (88%) had normal albumin-adjusted serum calcium levels. Additionally, 70 (96%) were no longer reliant on conventional therapy, which was defined as taking <600 mg/day of calcium and not taking active vitamin D. Improvements in eGFR were also sustained through Week 156: mean eGFR increased by 8.76 mL/min/1.73 m2 across all patients and by 13.98 mL/min/1.73 m2 in patients with baseline eGFR <60.1

Continued improvements were reported from baseline through Week 156. Palopegteriparatide was well-tolerated and exhibited no new safety signals. TEAEs were mild to moderate, and no serious events or discontinuations from the trial were due to the study drug.1

Palopegteriparatide has already been approved by the US Food and Drug Administration (FDA) to treat hypoparathyroidism in August of 2024, under the name YORVIPATH. Also developed by Ascendis Pharma, this treatment was a prodrug of parathyroid hormone (PTH[1-34]), administered once daily.2

The approval came in response to a New Drug Application including data from the phase 2 PaTH Forward and the first portion of the phase 3 PaTHway trial. At the time, palopegteriparatide was the first and only treatment for hypoparathyroidism in adults.2

References

1. New 3-Year Phase 3 Data Confirmed Sustained Response to TransCon PTH (Palopegteriparatide) Therapy in Adults with Hypoparathyroidism, Including Improvements in Biochemistries, Kidney Function, and Quality of Life. Ascendis Pharma. July 14, 2025. Accessed July 14, 2025. https://investors.ascendispharma.com/news-releases/news-release-details/new-3-year-phase-3-data-confirmed-sustained-response-transconr

2. FDA Approves YORVIPATH (Palopegteriparatide) as the First and Only Treatment for Hypoparathyroidism in Adults. Ascendis Pharma. August 12, 2024. Accessed July 14, 2025. https://investors.ascendispharma.com/news-releases/news-release-details/fda-approves-yorvipathr-palopegteriparatide-first-and-only