Palopegteriparatide Improves Skeletal Dynamics in Adults With Chronic Hypoparathyroidism: 162-week Results From the Phase 2 PaTH Forward Trial

Introduction: Chronic hypoparathyroidism is associated with low bone remodeling that predisposes to increased bone mineral density (BMD) due to the missing physiological effects of parathyroid hormone (PTH). Palopegteriparatide (YORVIPATH; TransCon PTH) is approved by the European Commission as a PTH replacement therapy for adults with chronic hypoparathyroidism. This analysis investigated skeletal endpoints in response to treatment with palopegteriparatide through week 162 of the PaTH Forward trial.

Methods: PaTH Forward is a phase 2, randomized, double-blind, placebo-controlled 4-week trial followed by an ongoing 210-week open-label extension period. Serum bone turnover markers (BTM) of bone formation (procollagen type 1 N-terminal propeptide [P1NP]) and bone resorption (C-terminal telopeptide of type 1 collagen [CTx]) and BMD measured by DXA at the lumbar spine, total hip, femoral neck, and 1/3 distal radius were assessed at baseline and at regular intervals through week 162

Results: At baseline, participants enrolled in PaTH Forward (N=59) had a median (range) duration of hypoparathyroidism of 9 (1-39) years; mean (SD) age was 50 (12) years, and 81% were female. Fifty-seven (97%) participants continued to receive palopegteriparatide treatment through week 162 of the trial. At week 162, 52 (91%) participants achieved independence from conventional therapy (≤600 mg/day oral calcium and no active vitamin D); mean serum calcium remained in the normal range (8.3-10.6 mg/dL) from baseline through week 162 (mean [SD] at week 162, 8.9 [0.4] mg/dL). With exposure to palopegteriparatide, mean CTx and P1NP initially increased, with peaks at weeks 12 and 26, respectively, declined thereafter, and remained stable above baseline levels through week 162 ([Fig. 1]). With palopegteriparatide treatment, mean BMD Z-scores declined from elevated baseline levels characteristic of chronic hypoparathyroidism toward age and sex-matched norms and remained above zero through week 162 ([Fig. 1]). Trends in BMD changes were consistent regardless of age, sex, menopausal status, and duration of hypoparathyroidism. Higher baseline BMD Z-scores were associated with greater declines in BMD over time. No new safety signals were identified.

Fig 1  Skeletal responses to palopegteriparatide.

Discussion: These 162-week results show that continued PTH replacement therapy with palopegteriparatide sustains temporal changes trending toward a new skeletal steady state closer to age-appropriate norms in adults with chronic hypoparathyroidism.

Keywords: Parathormon, Hypoparathyreoidismus, bone remodeling, CTx, P1NP, BMD, Palopegteriparatid

Korrespondenzadresse: Christopher Klisch, Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik II, Fetscherstr. 74, 01307 Dresden, Deutschland, E-Mail: [e-mail]

Conflict of interest

Elena Tsourdi führt klinische Studien mit Alexion, Amgen, Amolyt, Ascendis, Kyowa Kirin und UCB durch und erhielt Honorare für Vorträge oder Erstellung von Lehrmaterial von Alexion, Amgen, Ascendis und UCB.

Publication History

Article published online:
21 March 2025