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]

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Artikel online veröffentlicht:
21. März 2025