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The first PTH replacement designed to release the hormone continuously — inactive until the linker cleaves in the body.
Also known as: TransCon PTH · Yorvipath · PTH(1-34) prodrug
Part of the Foundational & therapeutic peptides cluster
Overview
Palopegteriparatide (TransCon PTH, Yorvipath) is a prodrug of parathyroid hormone: the active PTH(1-34) fragment is attached N-terminally to a polyethylene glycol carrier and released as the linker cleaves, giving sustained daily exposure. It is approved for chronic hypoparathyroidism in adults (EMA 2023, FDA 2024). In the phase 3 PaTHway trial, 95% of participants were independent of active vitamin D and high-dose calcium at week 52.
Source & context
Biological / chemical source: Synthetic PTH(1-34) attached to an inert polyethylene glycol carrier through a cleavable linker
Primary research or clinical context: Approved PTH replacement therapy for chronic hypoparathyroidism in adults (EMA 2023, FDA 2024)
What palopegteriparatide is
Palopegteriparatide is a synthetic parathyroid hormone mimetic built as a prodrug. Structurally it is the 1–34 fragment of the mature 84-residue human parathyroid hormone (PTH) — the same fragment as teriparatide — with a polyethylene glycol carrier attached at the N-terminus through a linker designed to cleave slowly under physiological conditions. Until that linker is cut, the molecule cannot activate the PTH receptor; as it cleaves, free PTH(1-34) is released and the effect is sustained across the day. The IUPHAR/BPS Guide to Pharmacology records it as an authorised sustained-release PTH replacement for hypoparathyroidism. It is marketed as Yorvipath and was developed under the name TransCon PTH.
Why sustained release matters in hypoparathyroidism
Hypoparathyroidism is inadequate PTH secretion or action, most often after neck surgery, producing low serum calcium, high phosphate and excessive urinary calcium (Khan & Khan, Nature Reviews Endocrinology 2025). Conventional therapy — oral calcium salts and active vitamin D — raises serum calcium without restoring the hormone, carries a high pill burden, produces calcium fluctuations and is associated with renal complications such as nephrocalcinosis over time. PTH replacement addresses the deficit itself: the 2025 best-practice recommendations note that it can normalise serum calcium, lower phosphate and, for the long-acting analogue palopegteriparatide, normalise urinary calcium (Khan et al., Metabolism 2025).
Structure and engineering
The active moiety is PTH(1-34), the N-terminal fragment that carries the receptor-activating residues. Attaching a large inert PEG carrier through a self-cleaving linker converts a peptide with a short circulating life into a depot that releases hormone continuously after a single daily subcutaneous injection. The design goal, per the IUPHAR record, is continuous exposure rather than the once-daily peak-and-trough profile of unmodified PTH(1-34). The teriparatide profile on this site covers the unmodified fragment and its use in osteoporosis; the two share a sequence but not a pharmacokinetic profile or an indication.
Clinical evidence: the PaTHway phase 3 trial
PaTHway randomised 82 adults with chronic hypoparathyroidism to palopegteriparatide or placebo for a 26-week double-blind period, followed by an open-label extension in which all participants received the drug once daily (Khan et al., Journal of Bone and Mineral Research 2023). At week 52, 81% (63/78) met the multicomponent endpoint of normal serum calcium plus independence from conventional therapy, 95% (74/78) were independent of conventional therapy, and none required active vitamin D; mean 24-hour urine calcium fell from 376 to 195 mg/day, and bone mineral density Z-scores moved toward age- and sex-matched norms (Clarke et al., Journal of Clinical Endocrinology & Metabolism 2025). Most adverse events were mild or moderate and none led to discontinuation during the extension.
| Outcome | Result |
|---|---|
| Normal serum calcium + independence from conventional therapy | 81% (63/78) |
| Independence from conventional therapy | 95% (74/78) |
| Participants needing active vitamin D | 0 |
| 24-h urine calcium, mean | 376 → 195 mg/day |
| eGFR change from baseline, mean | +9.3 mL/min/1.73 m² |
Kidney function
Because renal impairment is a recognised long-term complication of conventional therapy, a post hoc analysis of PaTHway examined estimated glomerular filtration rate over 52 weeks. Treatment was associated with a mean increase in eGFR of 9.3 mL/min/1.73 m² from baseline (P < 0.0001), with 43% of participants gaining at least 10 mL/min/1.73 m²; over 95% of participants remained enrolled at week 52, and among them 86% maintained normocalcaemia (Rejnmark et al., Advances in Therapy 2024). The authors present this as a signal that replacing PTH while reducing calcium and vitamin D loads may help protect renal function; it is a secondary analysis, not a primary endpoint.
Real-world use and regulatory status as of September 2026
Palopegteriparatide is approved by the EMA (2023) and the FDA (2024) for chronic hypoparathyroidism in adults. Early US real-world data from the expanded access programme (123 consenting patients, most previously treated with short-lived PTH analogues) describe titration alongside conventional therapy with assessment of calcium levels and adverse events over 12 months (Graham et al., Endocrine Practice 2025). ClinicalTrials.gov lists ongoing phase 3 studies, including one in adolescents and a cardiovascular-effects study of PTH analogues in chronic hypoparathyroidism. It is a prescription medicine; this page is educational and not treatment guidance.
How it relates to other peptides on this site
Teriparatide is the same PTH(1-34) fragment without the carrier, dosed once daily for osteoporosis, where intermittent peaks build bone. Abaloparatide is a PTH-related-protein analogue with the same receptor and indication. Palopegteriparatide takes the identical fragment and changes the exposure profile to continuous, which is what a replacement therapy for a missing hormone requires. Calcitonin, also on this site, acts in the opposite direction on serum calcium.
Structure & chemistry
Molecular identity & reference confidence
Reference mass unavailable
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Amino acids 1–34 of mature human parathyroid hormone (84 aa), N-terminally PEGylated
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-09-07
- Receptors
- PTH1 receptor (via released PTH(1-34)); the intact prodrug is inactive at the receptor
- Backbone
- Amino acids 1–34 of mature human parathyroid hormone (84 aa), N-terminally PEGylated
- Status
- Approved: EMA (2023), FDA (2024) for chronic hypoparathyroidism in adults
- IUPHAR ligand: 13484
- CAS RN: 2222514-07-8
Chemistry values: curated profile, IUPHAR/BPS Guide to Pharmacology · fetched 2026-09-07.
Clinical development snapshot
ClinicalTrials.gov lists 9 registered studies with “Palopegteriparatide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT07081997 | A Phase 3 Randomized Clinical Trial to Investigate the Safety and Efficacy of Palopegteriparatide at Doses Gre | Phase 3 | recruiting | 2026-09-30 |
| NCT07264634 | A Study to Assess the Amount of Palopegteriparatide in Breast Milk of Lactating Females Requiring YORVIPATH® ( | — | recruiting | 2026-08-07 |
| NCT07706764 | A Study to Test the Effects and Safety of Palopegteriparatide in Adolescents With Long-term Hypoparathyroidism | Phase 3 | recruiting | 2026-07-28 |
| NCT07707479 | Cardiovascular Effects of Parathyroid Hormone Analogues in Chronic Hypoparathyroidism | — | active not recruiting | 2026-07-16 |
| NCT04701203 | A Trial Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Daily in Adults With | Phase 3 | completed | 2026-07-07 |
| NCT07345494 | A Global Pregnancy Registry to Assess Maternal, Fetal, and Infant Outcomes Following Exposure to YORVIPATH® (P | — | recruiting | 2026-03-02 |
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- IdentifiersCross-linked to IUPHAR ligand 13484.
- TrialsClinicalTrials.gov snapshot added: 9 registered studies, highest phase 3.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Palopegteriparatide
What is Palopegteriparatide?+
Palopegteriparatide (TransCon PTH, Yorvipath) is a prodrug of parathyroid hormone: the active PTH(1-34) fragment is attached N-terminally to a polyethylene glycol carrier and released as the linker cleaves, giving sustained daily exposure. It is approved for chronic hypoparathyroidism in adults (EMA 2023, FDA 2024). In the phase 3 PaTHway trial, 95% of participants were independent of active vitamin D and high-dose calcium at week 52.
What Canadian product status is recorded for Palopegteriparatide?+
Canadian product status for Palopegteriparatide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Palopegteriparatide?+
Palopegteriparatide is commonly described as approximately 34 amino acids (PEGylated parathyroid hormone prodrug).
What is palopegteriparatide?+
A prodrug of parathyroid hormone (PTH(1-34) attached to a PEG carrier through a cleavable linker) that releases the active hormone continuously. It is approved for chronic hypoparathyroidism in adults, marketed as Yorvipath.
Is palopegteriparatide approved?+
Yes — by the EMA in 2023 and the FDA in 2024, for chronic hypoparathyroidism in adults.
How is palopegteriparatide different from teriparatide?+
Both contain PTH(1-34). Teriparatide is the bare fragment used intermittently for osteoporosis; palopegteriparatide is a PEGylated prodrug designed for continuous release as a hormone replacement in hypoparathyroidism.
What did the PaTHway trial show?+
At week 52, 95% of participants were independent of active vitamin D and high-dose calcium, 81% also had normal serum calcium, urine calcium roughly halved, and eGFR rose by a mean of 9.3 mL/min/1.73 m².
Does palopegteriparatide affect the kidneys?+
A post hoc PaTHway analysis found a mean eGFR increase of 9.3 mL/min/1.73 m² over 52 weeks; this is a secondary analysis, not a primary endpoint.
Related peptides
References & further reading
- 1.Khan AA et al. (2023). Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26-Week Results From the Phase 3 PaTHway Trial. J Bone Miner Res
- 2.Clarke BL et al. (2025). Efficacy and Safety of TransCon PTH in Adults With Hypoparathyroidism: 52-Week Results From the Phase 3 PaTHway Trial. J Clin Endocrinol Metab
- 3.Rejnmark L et al. (2024). Palopegteriparatide Treatment Improves Renal Function in Adults with Chronic Hypoparathyroidism: 1-Year Results from the Phase 3 PaTHway Trial. Adv Ther
- 4.Graham T et al. (2025). Early U.S. Real-World Treatment Patterns and Outcomes in Palopegteriparatide Treatment for Patients With Hypoparathyroidism. Endocr Pract
- 5.Khan S, Khan AA (2025). Hypoparathyroidism: diagnosis, management and emerging therapies. Nat Rev Endocrinol
- 6.Khan AA et al. (2025). Best practice recommendations for the diagnosis and management of hypoparathyroidism. Metabolism
- 7.Bonnet AL et al. (2025). Advances in Parathyroid Hormone-based medicines. J Bone Miner Res