Improved Skeletal Dynamics in Adults Treated With Palopegteriparatide for Hypoparathyroidism: 52-Week Analysis of Phase 3 PaTHway Trial

Introduction: Evaluate the temporal changes in and relationship between skeletal endpoints in response to palopegteriparatide (TransCon PTH), a prodrug with sustained release of PTH(1-34), in individuals with chronic hypoparathyroidism.

Methods: PaTHway is a phase 3 trial of TransCon PTH with a randomized, placebo-controlled 26-week blinded period and 156-week open-label extension. Serum bone turnover markers (BTM) of bone formation (procollagen type 1 N-terminal propeptide [P1NP]) and bone resorption (C-telopeptide [CTx]) were assessed at baseline and weeks 12, 26, 38, and 52. Bone mineral density (BMD) was assessed by DXA at the lumbar spine, total hip, and distal 1/3 radius at baseline, weeks 26 and 52. Skeletal endpoints are reported herein for participants randomized to TransCon PTH with week 52 data (n=59).

Results: At baseline, participants in the TransCon PTH group had a mean (SD) age of 49 (13) years; 75% were female, 41% of whom were postmenopausal. Through week 52, 81% (48/59) maintained 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). TransCon PTH treatment initially increased CTx and P1NP; responses peaked by week 12 and 26, respectively, and then declined through week 52 (Figure). From weeks 26 to 52, BTM decreased most in those with the highest values at week 26. Mean baseline BMD was high, as expected in hypoparathyroidism. With exposure to TransCon PTH over 52 weeks, mean BMD Z-scores and T-scores declined from above 0 toward age- and/or sex-matched norms at the lumbar spine and total hip, with a smaller magnitude of change from week 26 to 52 (Figure). Changes in BMD at the spine and hip were consistent across age, sex, and postmenopausal status, and at week 26 were inversely correlated with changes in P1NP and CTx at week 12 (R: -0.23 to -0.48).

Discussion: TransCon PTH treatment resulted in mobilization of calcium from the low bone turnover state in adults with hypoparathyroidism. Increases in BTM were correlated with declines from disease-elevated BMD at baseline. After week 26, BTM normalized toward sex and menopausal status appropriate levels and corresponded to lesser declines in BMD through week 52, similar to the results through week 110 in the Phase 2 PaTH Forward trial. These 52-week results reflect temporal changes trending toward a new skeletal steady state closer to age-appropriate norms with continued use of TransCon PTH in hypoparathyroidism.

Keywords: hypoparathyroidism, parathyroid hormone, hormone replacement

Korrespondenzadresse: Elena Tsourdi, Technische Universität Dresden Medical Center, Fiedlerstraße 27, 01307 Dresden, Germany, E-Mail: [e-mail]

Publication History

Article published online:
13 March 2024