All peptides / Muscle and bone
Palopegteriparatide
Long-acting PTH prodrug
Also Yorvipath, TransCon PTH, TransCon-PTH, Yorvipath injection, Long-acting PTH
- Evidence
- AStrong human evidence
- FDA status
- FDA approvedas of 2026-10-26
- Route
- Injection
- Studies cited
- 1 human0 animal or cell
It is a daily injection for people whose body makes too little parathyroid hormone, which controls calcium. In a trial of 84 adults, about 79% reached normal calcium without calcium pills, versus 5% on placebo.
Sold for
Palopegteriparatide is the first replacement therapy that lets most people with hypoparathyroidism stop taking handfuls of calcium and active vitamin D.
Studies say
A placebo-controlled phase 3 trial showed about four in five patients reached normal calcium without conventional supplements, versus one in twenty on placebo, which is A-grade support for the approved use.
Why grade A. Approval rests on the PaTHway phase 3 trial, a randomized, double-blind, placebo-controlled study in 84 adults with hypoparathyroidism, in which the composite endpoint of normal calcium without conventional therapy was met by a large majority on drug and almost none on placebo. The trial was short at 26 weeks and open-label extension data are what carry the long-term story. 12
FDA. Approved in 2024 as Yorvipath for the treatment of hypoparathyroidism in adults, given as a once-daily subcutaneous injection. The label carries a warning about a potential osteosarcoma risk based on rat studies of parathyroid hormone analogs. 2
Written from 2 cited sources. Fact-checked 2026-10-27: 16 claims checked, 3 corrected. Last refreshed 2026-10-27. Not physician reviewed.
What this means for you
- What people take it for
- Too little parathyroid hormone (low calcium)
- Can a US doctor prescribe it?
- Yes, FDA approved for low parathyroid hormone in adults.
- Properly tested in people?
- Yes, in a controlled trial of 84 adults.
Evidence checklist
- Randomised controlled trial PaTHway, double-blind placebo-controlledyes
- Human study over 100 people PaTHway enrolled 84 adultsno
- More than one research group Sponsor trial and its extensionno
- Clinical outcomes, not surrogate markers Calcium and supplement independence measuresno
- Human safety data beyond case reports Calcium swings; rat osteosarcoma warningyes
Drawn from the cited studies below. A dash means the sources give no information.
What it is
Palopegteriparatide is a prodrug of parathyroid hormone. The active molecule is PTH(1-34), the same fragment as teriparatide. A slowly breaking linker attaches it to a large polyethylene glycol carrier. In the body, the linker releases PTH at a steady rate. So one daily injection gives hormone levels around the clock, with no brief spike. Ascendis Pharma developed it as TransCon PTH. It sells it as Yorvipath. 12
It treats hypoparathyroidism. In this condition, the parathyroid glands fail, usually after neck surgery, and blood calcium falls. Until 2024, the standard US treatment was high doses of calcium and active vitamin D. These control calcium poorly and strain the kidneys. 1
How it works
Parathyroid hormone keeps blood calcium in range in three ways. It pulls calcium from bone. It tells the kidney to hold on to calcium and shed phosphate. It switches on the kidney enzyme that activates vitamin D. People without the hormone need large oral doses of calcium and vitamin D. Even so, their levels swing high and low. Replacing PTH directly has been hard because its half-life is short. An injection of plain PTH acts for a few hours. The prodrug design keeps PTH in the normal range for a full day. The kidney needs this to normalize its handling of calcium. 12
What human research shows
PaTHway randomized 84 adults with long-term hypoparathyroidism, about three to one. They got palopegteriparatide or placebo for 26 weeks. Both groups kept their usual therapy, which was then tapered. The main measure combined several goals. Blood calcium had to be normal. Patients had to stop active vitamin D and therapeutic calcium doses. They could not need more study drug in the final weeks. About 79 percent of patients on palopegteriparatide met it. About 5 percent on placebo did. Urinary calcium is chronically high on usual therapy and damages kidneys. On the drug, it fell into the normal range. Patient-reported symptom and quality of life scores also improved. 1
The label sums up the open-label extension of PaTHway. Among patients first randomized to the drug, 64% kept normal calcium at week 52. They also stayed free of active vitamin D and therapeutic calcium. At week 78, 66% did, when dose increases were allowed. 2
| Study | Model | Finding |
|---|---|---|
| PaTHway phase 3 (Khan 2023) | Humans, n=84 adults with hypoparathyroidism, randomized double-blind placebo-controlled, 26 weeks | About 79 percent on palopegteriparatide versus 5 percent on placebo achieved normal calcium independent of conventional therapy, with normalized urinary calcium. 1 |
| Yorvipath prescribing information | FDA label | Documents the approved indication, osteosarcoma warning and calcium monitoring requirements. 2 |
Safety
In PaTHway, these reactions were reported more often than with placebo: injection-site reactions, flushing and other vessel-widening symptoms, headache, diarrhea, back pain, high calcium and throat pain. Both high and low calcium can occur. This is most likely while usual therapy is being tapered. The label requires calcium checks. The osteosarcoma warning comes from rats. They got high doses of PTH analogs for most of their lifespan. No human cases have been tied to the drug. But the label advises against use in people at higher baseline risk. Examples are people with Paget's disease or earlier skeletal radiation. 12
The long-term safety question is bone. PTH builds bone, and the drug is meant for lifelong use. So extension studies are following bone density and bone quality. Hypoparathyroidism itself produces abnormally dense bone. Early data suggest density moves toward normal and does not fall. 1
Questions for your clinician
- Would this let me stop calcium and vitamin D, and how soon?
- How will my calcium be monitored while I taper other therapy?
- Does the osteosarcoma warning apply to my bone history?
Questions people ask
How is palopegteriparatide different from Natpara?
Natpara was full-length PTH(1-84), given once daily. It acted only briefly, so calcium still swung during the day. Palopegteriparatide releases PTH(1-34) continuously from a carrier, so levels are steadier. Natpara was also recalled in 2019. Its maker announced it would discontinue it. 12
Can patients stop calcium and vitamin D completely?
In the trial, most did. The goal required independence from active vitamin D and from therapeutic-dose calcium. About four in five patients met it at 26 weeks. Some people still take ordinary dietary-level calcium. 1
What is the osteosarcoma warning about?
Rats given PTH analogs for most of their lives developed bone tumors. After teriparatide reached the market, osteosarcoma was reported in some people treated with it. But observational studies in humans have not found a higher risk. The label advises against use in people whose baseline risk of bone cancer is already raised. 2
Is it the same as teriparatide?
The active fragment is the same, PTH(1-34). The formulation and purpose differ. Teriparatide is a short-acting daily injection. Patients use it for two years to build bone in osteoporosis. Palopegteriparatide is designed for steady, lifelong hormone replacement in hypoparathyroidism. 12
Citations
- Khan 2023, J Bone Miner Res: efficacy and safety of palopegteriparatide (TransCon PTH) in adults with hypoparathyroidism, PaTHway phase 3 trial pubmed.ncbi.nlm.nih.gov
- Ascendis Pharma: Yorvipath (palopegteriparatide) prescribing information ascendispharma.us