Abstract

Context

Conventional therapy for hypoparathyroidism aims to alleviate symptoms of hypocalcemia but does not address insufficient parathyroid hormone (PTH) levels.

Objective

Assess the long-term efficacy and safety of TransCon PTH (palopegteriparatide) for hypoparathyroidism.

Design

Phase 3 trial with a 26-week, double-blind, placebo-controlled period followed by a 156-week, open-label extension (OLE).

Setting

Twenty-one sites across North America and Europe.

Participants

A total of 82 adults with hypoparathyroidism were randomized and received study drug and 78 completed week 52.

Intervention(s)

All OLE participants received TransCon PTH administered once daily.

Main Outcome Measure(s)

Multicomponent efficacy endpoint: proportion of participants at week 52 who achieved normal serum calcium (8.3-10.6 mg/dL) and independence from conventional therapy (≤600 mg/day of elemental calcium and no active vitamin D). Other efficacy endpoints included patient-reported outcomes and bone mineral density. Safety was assessed by 24-hour urine calcium and treatment-emergent adverse events.

Results

At week 52, 81% (63/78) met the multicomponent efficacy endpoint, 95% (74/78) achieved independence from conventional therapy, and none required active vitamin D. Patient-reported outcomes showed sustained improvements in quality of life, physical functioning, and well-being. Mean bone mineral density Z-scores decreased toward age- and sex-matched norms from baseline to week 52. Mean (SD) 24-hour urine calcium excretion decreased from 376 (168) mg/day at baseline to 195 (114) mg/day at week 52. Most treatment-emergent adverse events were mild or moderate and none led to trial discontinuation during the OLE.

Conclusion

At week 52 of the PaTHway trial, TransCon PTH showed sustained efficacy, safety, and tolerability in adults with hypoparathyroidism.