Orphan drug improves blood calcium levels and reduces reliance on conventional hypoparathyroidism therapy in adults, PaTHway analysis shows
Presenter: Bart L. Clarke, MD, Mayo Clinic, Rochester, MN
Palopegteriparatide treatment in adults with hypoparathyroidism: final results of the phase 3 PaTHway trial. Presented June 13, 2026.
Palopegteriparatide, a parathyroid hormone prodrug given by subcutaneous injection, provided a durable response in adults with hypoparathyroidism through 182 weeks of treatment, during which most of them kept their serum calcium levels in the normal range and needed less conventional therapy, according to phase 3 data presented at ENDO 2026.
The US Food and Drug Administration approved palopegteriparatide injection for subcutaneous use in adults with hypoparathyroidism in 2024.
Multinational phase-3 trial of long-term palopegteriparatide
Hypoparathyroidism is a rare endocrine disease affecting an estimated 70,000 to 90,000 people in the United States. Caused by inadequate parathyroid hormone production, it can lead to serious complications, including neuromuscular symptoms, renal impairment, extraskeletal calcifications, and cognitive dysfunction.
Eighty-two adults with hypoparathyroidism at 21 European and North American sites participated in the PaTHway trial, which consisted of a 26-week, randomized, double-blind, placebo-controlled period followed by a 156-week open-label extension. Seventy-three participants (89%) completed the full open-label extension period.
Before randomization, participants completed an approximately 4-week screening period in which investigators adjusted their calcium and active vitamin D supplementation to achieve target albumin-corrected serum calcium levels of 7.8 to 10.6 mg/dL, magnesium levels of at least 1.3 mg/dL, and 25-hydroxyvitamin D levels of 20 to 80 ng/mL.
During the double-blind period, 61 participants received at least 1 dose of the study drug and 21 received at least one dose of placebo, both along with conventional therapy. Investigators adjusted the study drug and the conventional therapy according to the participants’ albumin-corrected serum calcium levels.
All participants in the open-label extension received palopegteriparatide once daily.
The efficacy endpoints were independence from conventional therapy (needing no more than 600 mg of elemental calcium daily and no active vitamin D) and achieving normal albumin-adjusted serum calcium levels (8.3–10.6 mg/dL).
Through week 182, the investigators assessed bone turnover markers, bone mineral density T scores and Z scores, and renal function as measured by estimated glomerular filtration rate. They also evaluated patient-reported symptoms, physical functioning, and daily life using validated hypoparathyroidism-specific measures throughout the open-label extension. Safety assessments included treatment-emergent adverse events, serum chemistries, and 24-hour urinary calcium levels.
Sustained efficacy and safety during extended treatment
Of the 73 participants who completed the open-label extension period, 70 (96%) kept their calcium level in the normal range without therapeutic doses of calcium or active vitamin D, and 65 (89%) maintained normal albumin-adjusted serum calcium levels, with a mean value of 8.8 mg/dL at 182 weeks.
Bone turnover markers initially rose as anticipated and then stabilized within the normal range. Baseline bone mineral density Z scores, which were elevated at study entry, trended toward age- and sex-matched norms and remained stable after week 26 while staying above 0 through week 182. Patterns were similar regardless of the participants’ sex or menopausal status.
Symptoms, physical functioning, and daily life improved early in treatment and stayed better throughout the open-label extension period. The mean glomerular filtration rate increased from baseline and stabilized over time, and at week 182 it had increased by 11.0 mL/min/1.73 m². Elevated urinary calcium excretion normalized and remained within the normal range during long-term follow-up.
Most treatment-emergent adverse events were mild or moderate; 3 participants discontinued treatment because of treatment-emergent adverse events unrelated to the study drug.
Disclosures
No disclosures.
References
Clarke BL, Rubin M, Schwarz P, et al. Palopegteriparatide treatment in adults with hypoparathyroidism: final results of the phase 3 PaTHway trial. Presented at ENDO 2026, June 13, 2026, Chicago, IL.
US Food and Drug Administration. FDA approves new drug for hypoparathyroidism, a rare disorder (press release). August 9, 2024. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-new-drug-hypoparathyroidism-rare-disorder Accesed June 16, 2026.
Khan AA, Rubin MR, Schwarz P, et al. Efficacy and safety of parathyroid hormone replacement with transcon PTH in hypoparathyroidism: 26-week results from the phase 3 PaTHway trial. J Bone Miner Res 2023; 38(1):14–25. doi:10.1002/jbmr.4726
Ascendis Pharma. New 4-year data shows sustained response to TransCon® PTH (palopegteriparatide) therapy in adults with hypoparathyroidism (press release). May 12, 2025. https://investors.ascendispharma.com/news-releases/news-release-details/new-4-year-data-shows-sustained-response-transconr-pth Accessed June 16, 2026.