Palopegteriparatide Improves Skeletal Dynamics in Adults With Chronic Hypoparathyroidism: 162-week Results From the Phase 2 PaTH Forward Trial
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".