Palopegteriparatide: evidence, FDA status and research

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, attached through a slowly breaking linker to a large polyethylene glycol carrier. In the body the linker releases PTH at a steady rate, so one daily injection gives round-the-clock hormone levels with no brief spike. Ascendis Pharma developed it under the name TransCon PTH and sells it as Yorvipath. ¹²

It treats hypoparathyroidism, a condition in which the parathyroid glands fail, usually after neck surgery, and blood calcium falls. Until 2024 the standard treatment in the United States was high doses of calcium and active vitamin D, which control calcium poorly and strain the kidneys. ¹

How it works

Parathyroid hormone keeps blood calcium in range by pulling calcium from bone, telling the kidney to hold on to calcium and shed phosphate, and switching on the kidney enzyme that activates vitamin D. People without the hormone need large oral calcium and vitamin D doses to compensate, and still swing between high and low levels. The problem with replacing PTH directly has been its short half-life; an injection of plain PTH acts for a few hours. The prodrug design keeps PTH in the physiologic range for a full day, which is what the kidney needs to normalize calcium handling. ¹²

What human research shows

PaTHway randomized 84 adults with chronic hypoparathyroidism, about three to one, to palopegteriparatide or placebo for 26 weeks, with both groups continuing conventional therapy that was then tapered. The primary endpoint was a composite: normal blood calcium, independence from active vitamin D and from therapeutic calcium doses, and no increase in study drug in the final weeks. About 79 percent of patients on palopegteriparatide met it, against about 5 percent on placebo. Urinary calcium, which is chronically high on conventional therapy and damages kidneys, fell into the normal range on drug. Patient-reported symptom and quality of life scores also improved. ¹

In the open-label extension of PaTHway, summarized in the label, 64% of the patients first randomized to the drug kept normal calcium and independence from active vitamin D and therapeutic calcium at week 52, and 66% at week 78, 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

The adverse reactions reported more often than with placebo in PaTHway were injection-site reactions, flushing and other vasodilatory symptoms, headache, diarrhea, back pain, high calcium and throat pain. Both high and low calcium can occur, especially while conventional therapy is being tapered, and the label requires calcium monitoring. The osteosarcoma warning comes from rats given high doses of PTH analogs for most of their lifespan; no human cases have been attributed to the drug, but the label advises against use in people at elevated baseline risk, such as those with Paget's disease or prior skeletal radiation. ¹²

The long-term safety question is bone. PTH is anabolic and the drug is intended for lifelong use, so bone density and bone quality are being followed in extension studies. Hypoparathyroidism itself produces abnormally dense bone, and 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, and its short duration meant calcium still fluctuated through the day. Palopegteriparatide releases PTH(1-34) continuously from a carrier, giving steadier levels. Natpara was also recalled in 2019 and its manufacturer announced its discontinuation. ¹²

Can patients stop calcium and vitamin D completely?

In the trial most did. The endpoint required independence from active vitamin D and from therapeutic-dose calcium, and 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. Osteosarcoma has been reported in people treated with teriparatide after marketing, but observational studies in humans have not found an increased 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), but the formulation and purpose differ. Teriparatide is a short-acting daily injection used 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