Palopegteriparatide (Yorvipath): uses, how it works and side effects

Palopegteriparatide replaces missing parathyroid hormone in adults whose parathyroid glands are underactive. The goal of treatment is to keep blood calcium within the normal range and to reduce the need for extra calcium and active vitamin D. The medicine is injected under the skin once a day.

What is palopegteriparatide?

Palopegteriparatide is sold under the brand name Yorvipath and works as a long-acting replacement for parathyroid hormone. It uses a delivery system called TransCon: the active hormone component, PTH(1-34), is attached by a linker to a carrier that has no hormonal effect of its own. This bond breaks down gradually, so the hormone is released over the course of the day. The idea is that the body receives a steady supply of parathyroid hormone when the parathyroid glands cannot make enough.

Ascendis Pharma developed palopegteriparatide. It was approved in the United States in 2024.

How does palopegteriparatide work?

Palopegteriparatide starts out inactive. Only after injection does it gradually release active PTH(1-34). A drug precursor of this kind is called a prodrug. The slow release is meant to keep hormone levels even over 24 hours. With conventional teriparatide, by contrast, levels first rise sharply and then drop again quickly.

The released hormone binds to a docking site, the PTH-1 receptor. It acts on the kidneys, on the activation of vitamin D and on the bones, and in this way regulates the body’s calcium balance. In hypoparathyroidism, the underactivity of the parathyroid glands, it is meant to take over the job of the missing natural hormone.

Treatment aims to keep blood calcium within the normal range and to reduce the need for high-dose calcium and active vitamin D. In the Phase 3 PaTHway trial, most people treated with palopegteriparatide reached the combined study goal after 26 weeks: a normal calcium level and independence from conventional therapy with calcium and active vitamin D. The great majority met the study’s criterion for no longer needing these products. This does not mean, however, that they could do without any additional calcium intake at all. 1

Is palopegteriparatide FDA-approved?

Yes. The US Food and Drug Administration (FDA) approved palopegteriparatide in 2024 under the name Yorvipath for the treatment of hypoparathyroidism in adults. It had already been approved in Europe before that. The medicine is injected once a day subcutaneously, that is, under the skin. 2

The US prescribing information warns of a possible risk of osteosarcoma, a malignant bone tumor. The warning is based on studies of parathyroid hormone analogs in rats. Palopegteriparatide is not recommended for people at increased risk of this type of cancer.

What is palopegteriparatide prescribed for?

Doctors prescribe palopegteriparatide to adults with hypoparathyroidism as parathyroid hormone replacement therapy. Because the hormone is released evenly, blood calcium is meant to stay within the normal range. At the same time, treatment is intended to lower the need for supplemental calcium and active vitamin D. This makes palopegteriparatide an alternative to other forms of parathyroid hormone replacement.

What side effects can occur?

The prescribing information lists the following among the common side effects:

• Injection site reactions
• Sudden reddening of the skin with a feeling of warmth (flushing), lightheadedness, or a drop in blood pressure on standing up
• Headache
• Back pain
• Diarrhea
• A raised blood calcium level
• Sore throat

The more serious risks include:

• A possible risk of osteosarcoma; the warning is based on studies of parathyroid hormone analogs in rats
• Blood calcium that is too high or too low, especially when the dose is being adjusted
• Hypersensitivity reactions